ویروس قطعهای از نوکلئیک اسید است که درون یک پوشش پروتئینی محصور شدهاست. ویروسها از باکتریها بسیار کوچکتر هستند و تنها با میکروسکوپ الکترونی قابل مشاهدهاند. ویروس با استفاده از امکانات سلولی و یا خودش در سلولهای میزبان تکثیر میشود و فعالیت اصلی یاختههای میزبان را مختل میکند. ویروسها بسیاری از جانوران و گیاهان را مبتلا میکنند اما فقط برخی از آنها انسانها را بیمار میکنند. همچنین ویروسها در محیط خنثی ولی در سلولهای زنده تکثیر میکنند وانگل داخل سلولی میباشند.
دراواخر قرن ۱۹ میلادی دانشمندان به دنبال یافتن عامل بیماری موزائیک تنباکو بودند. دیمیتری ایوانفسکی درسال۱۸۹۲ توانست قابل انتقال بودن عامل بیماری موزانیک توتون را ثابت کند. او پس از عبور دادن عصاره برگهای گیاه عفونت زده از صافی غیر قابل عبور برای باکتریها، آنرا بروی برگهای گیاه سالم توتون پخش کرده و بیماری موزانیک توتون را انتقال داده ایجاد بیماری درگیاه سالم نمود. آنان دریافتند که از گیاه آلوده مولدی قادر است که گیاهان سالم را بیمار کند. بنابراین عامل بیماری هرچه که بود از باکتریها بسیار کوچکتر بود. در سال ۱۹۳۵ زیستشناسی به نام وندل استنلی توانست ویروس موزاییک تنباکو را تخلیص کند. ویروس خالص شده اگر چه به شکل بلور بود اما باز هم میتوانسات گیاهان سالم را بیمار کند. چون تبلور یک از ویژگیهای مواد شیمیایی است بنابراین میتوان نتیجه گرفت که ویروس داخل یاختهها موجودی زنده وخارج یاختهها یک ماده شیمایی است نه یک موجود زنده.
تباین ویروسها با کلیه میکروبهایی شناخته شده، آنان را در زیست شناسی میکربی از مقام و جایگاه ویژه و رده بندی جداگانهای برخوردار کردهاست. ساختمان ویروسها محدود است به ژنوم و پوششی ار پروتئین به دور آن. درشماری از ویروسها لایهای از لیپو پروئین و لیپوپلی ساکارید نیز مضافا برای حفاظت پوشش پروتئینی بدورآن قرارمیگیرد. ویروسها برای تکثیر باید به داخل سلولی نفوذ کرده برنامه تولیدی سلول را بنفع خود تغییرداده و کارگاه پروتئین سازی سلول را همه جانبه برای تولید پروتئینها و آنزیمهای لازم بکار گیرند. ویروسها درعین کوچکی با داشتن ژنهای کافی مراحل بسیارپیچیده تکثیرخودرا درسلول میزبان یا به گروگان گرفته شده به سهولت هدایت و کنترول میکنند و انگل وار تکثیر میشوند. ژنوم ویروسها عبارت است از نوعی اسید نوکلئیک که بر مبنای نوع آن، ویروسها به دو دسته تقسیم میشوند. ویروسهای حاوی "آر ان آ " را یبونوکلئیک اسید RNA و ویروسهای حاوی دیانای دزاوکسی رایبونوکلئیک اسید. DNAعفونت زایی ویروسها فقط و فقط حاصل فعالیت داخل سلولی اسید نوکلئیک یا ژنوم آنهاست به این جهت درخارج سلول ویروس و ژنومش عاری ازهرگونه فعالیت بوده و یک مولکول بزرگ محسوب میشود. ژنوم بسیاری ویروسها بصورت رشته یا کلاف داخل پوشش پروتئینشان که اختصاصاَکاپسید کپسیدنامیده میشود قراردارد. این پوشش پروتیینی یکپارچه نبوده بلکه از ذرات یا واحدهای کوچکتری بنام کاپسومر Capsomer ساخته میشود. کاپسومرها پس ازبهم پیوستن کاپسیدرا تشکیل میدهند و فرم مخصوص آن بستگی به نوع ویروس وساختار آن دارد. در برخی ویروسها ژنوم بصورت مارپیچی سنتز شده و کاپسومرها آنرا بطور منظم پوشش میدهند، طوریکه نوکلئوکاپسید ویروس حالت فنری یا هلیکال بخود میگیرد. علاوه براین ژنوم و کاپسید (نوکلئوکاپسید) بیش ازنیمی از ویروسها دارای غلاف (به انگلیسی: Envelop) از لیپوپروتئین و لیپوپولی ساکارید ند. در این مورد هم ویروسها بدودسته تقسیم میشوند. گروه غلافدار و گروه بدون غلاف. غلاف ویروسها ازتنوع بسیاری برخورداراست که بطورمفصل به آن خواهیم پرداخت. اندازه، شکل، حجم و ساختمان ویروسها بسیار متنوع و متفاوت است. ویروسها برخی کروی، بعضی مخروطی و بسیاری از اشکال هندسی مانند برخوردارند، ازآن جمله میتوان فرم مکعبی یا پلی هدرون را مثال زد. قطر کوچکترین ویروسها۲۰ نانومترو بزرگترین آنها۴۵۰ نانومتر گذارش شده (نانومتر عبارت است ازیک میلیونیوم میلیمتر). ویروسهای بزرگ (ویروسهای آبله) ازساختمانی نسبتا پیچیده یا مرکب (کمپلکس) برخوردارند وهمچون باکتریها ابداَ از صافی (فیلترچینی) عبور نمیکنند. درصورتیکه مابقی گذرای صافی چینی اند. ویروسها فقط به علت داشتن اطلاعات ژنتیکی برای تولیدمثل به جانداران شبیهاند. در واقع ویروسها انگل اجباری هستند. دستاوردهای فوق تائیدیست برای اینکه، برخلاف کلیه موجودات زنده اعم از تک سلولی یا بسیار سلولی وپروکاریونت ویوکاریونتها، ویروسها فاقد ساختمان سلولی بوده عاری از هرگونه فعل وانفعالات شیمیایی، آنزیمی و متابولیسم سلولی اند وبا فقدان ملزومات مشابه سازی، هرگز قادربه تکثیر و مشابه سازی خود نیستند. آنها را باید خارج از سلول زنده یک ماکروملکول مرکب یا یک واحد عفونت زا بشمارآورد. آنها باتوجه به اینکه ماکروملکولهای مرکبند یعنی دارای زنجیره اسید نوکلئیک و حفاظ پروتئینی و احتمالاُ غلافی از لیپوپروتئین و لیپولی ساکارید اند، آمادهاند به محض تماس با سلول میزبان و پس از مراحل جذب، دخول وآزادی ژنوم دستگاه پروتئین سازی میزبان را در اختیار گرفته و مراحل کلی تکثیر شانرا به کمک سیستمهای سلولی (ترانسکریپسیون و ترانسلاسیون) ترتیب دهند. سلولها اعم از ازپروکاریونت و یوکاریونتها میتوانند سلول میزبان اجباری ویروسها گردند. هرنوع سلولی پذیرای هر ویروسی نبوده، انحصارا ویروس آشنا بخود راپذیرا میباشد.
چرخه همانند سازی ویروسها از آلوده شدن سلول میزبان آغاز میشود و با رهاسازی ذرات ویروسی ایجادشده بالغ خاتمه مییابد.
ویروسها به علتِ فقدانِ ساختمانِ سلولی و هرگونه متابولیسم و فعل وانفعالِ شیمیایی، قادر به مشابه سازی خود نبوده و برای این عمل میباید به داخل سلولی حساس راه یافته و محتاجِ انرژی و دستگاهِ پروتئین سازیِ سلولِ زنده میباشند. انتقالِ ویروس به داخلِ سلول فقط توسطِ سلول امکانپذیر است و این عمل فقط توسطِ سلولِ حساس وحاملِ گیرندههای (رسپتورهای) آشنا به ویروس انجام میگیرد. سلولهائی که این نوع گیرندهها را برای جذبِ ویروس آماده دارند احتمالاً میتوانند به انتقالِ انواعِ مختلفِ ویروسها بپردازند، در غیر اینصورت سلول در مقابلِ ویروس مقاوم بوده و هرگونه تماسی با ویروس بی نتیجه خواهد بود. با دخول به سلول و پوشش برداری توسطِ آنزیمهایِ سلول، فعالیتِ اسیدنوکلئیک ویروس آغاز میگردد. اسیدنوکلئیکِ ویروس ژنهای کافی برایِ مهارنِمودنِ متابولیسمِ سلولِ میزبان را دارا بوده و به کمکِ آن احتیاجاتِ فعل و انفعالاتِ شیمی حیاتی، برای تکثیرِ خود را توسطِ سلولِ میزبان تامین میکند. پس از آلوده شدنِ سلولِ میزبان تکثیر ویروسها میتواند در دو نوع چرخه انجام گیرد :
گاهی ویروس پس از دخول به سلول پس ازطی مراحل اولیه و آزادشدنِ ژنوم یا اسیدنوکلئیک، به عوضِ تولید ژنوم وپروتئین ویروس، خود را درونِ کروموزومِ میزبان جای میدهد که در این حالت به ان پرو ویروس میگویند با هر بار تقسیم سلولی، پرو ویروس نیز تقسیم میشود. در این نوع چرخه بدونِ آنکه سلولِ میزبان تخریب شود ژنومِ ویروسی تکثیر پیدا میکند که گاهی این مرحله بدون آنکه سلولِ میزبان تخریب شود به تولیدِ ویروسِ کامل پرداخته و ویروسهای نوزاد را به خارجِ سلول هدایت میکند.
دراین مرحله سلولِ میزبان پس ازانجامِ تکثیر ویروس به کلی تخریب شده از این راه ویروسها ازسلول میزبان آزاد میشوند.
تکثیر ویروسها مراحل مختلفی را طی میکند که به شرح آن میپردازیم[ویرایش]
جذب و اتصال[ویرایش]
ویروس با غشاء سلولی تماس پیدا نموده گیرندههای (ریسپتورهای) آشنا و اختصاصی سبب جذب واتصال ویروس شده و شروع عفونت پایه گذاری میشود. حرارت محیط، پی اچ مناسب، نیروی الکترواستاتیک و وجود نمکهای معدنی درجذب ویروس و اتصال به رسپتورهای آشنای سطح سلول از اهمیت زیادی برخوردارند. نوع رسپتورهای آشنا برای ویروسهای مختلف یکسان نیست برای مثال ویروس فلج اطفال جذب نوعی لیپوپروتئین و ویروس آنفولانزا جذب موکوپروتئین سلول میگردد. همچنین رسپتور ویروس HIV مولکول CD4 ورسپتور ویروس ابشتن بار مولکولCD21 و رسپتوررینوویروس مولکول ICAM-1 میباشد. اما هرسلولی میتواند بمرور گیرنده لازم برای جذب ویروس جدیدی بسازد.
داخل شدن (ورود به سلول)[ویرایش]
ویروسهای غلافدار در این مرحله بطور کامل جذب غشاء سلولی میشوند. غلاف ویروس با غشاء سلولی یکی شده ونوکلئوکاپسید ویروس از غشاء سلولی عبور کرده وارد سیتوپلاسم سلول میشود. درمورد ویروسهای بدون غلاف باید ذکر شود، که گرچه یروس کوچکترین کاری نمیکند اما این سلول است که ویروس را بطور کامل به داخل سیتوپلاسم منتقل میکند. ویروس که در داخل سلول جای گرفت، از او پوشش برداری به عمل میاید. در این مرحله عمل بلع یا پینوسینوزانجام میشود.
پس از دخول ویروس به سلول، در داخل سیتوپلاسم و تحت تاثیرآنزیمهای داخل سلولی پوشش پروتئینی ویروس ازهم گسسته و اسید نوکلئیک آزاد میگردد. ازآغاز تا این مرحله را میتوان با کمک میکروسکوپ الکترونی تغییرات ویروس را دنبال کرده، مشاهده نمود.
اسید نوکلئیک آزاد شده ویروس به قطعات کوچکتری تقسیم شده و پس از اندک زمانی کمترین اثری از ژنوم ویروس قابل رؤیت نخواهدبود. ازاین پس اسید نوکلئیک ویروس فرمانروای سلول عفونت زده بوده و کنترل دستگاه پروتئین سازی سلول را برای تکثیر خویش هدایت میکند. در این مراحل میتوان ویروس را یک واحد زنده تلقی نمود و یا به عبارت دیگر اسید نوکلئیک ویروس یک واحد زنده محسوب میشود.
تکثیر یا بیوسنتز[ویرایش]
با سنتز و ساخت و سازآنزیمهای لازمه تکثیر، فعالیت اسید نوکلئیک ویروس در داخل سیتوپلاسم سلولی شروع شده، آنزیمها فعالیت خود را برای جلوگیری ازتولید پروتئین و اسید نوکلئیک سلولی آغازمیکنند. در گاهی موارد تولید پروتئین و اسید نوکلئیک سلولی به کلی متوقف نشده فقط به نحو کنترل شده محدود میگردد. به هر حال مراحل ترانسلاسیون و ترانسکریپسیون برای بیوسنتز و رپلیکاسیون ویروس با تولید وساخت پروتئین و اسید نوکلئیک ویروس در مراکز مشخصی آغاز میگردد. مراکز تولید با توجه به نوع ویروس هر کدام در گوشهای از سلول، گهی درداخل سیتوپلاسم و گاهی در داخل هسته سلول تشکیل شده، آماده تهیه و تولید ویروس و مرحله بعدی آن میگردند.
تکمیل شدن (کامل شدن)[ویرایش]
پس از تولید و سنتز پروتئین و اسید نوکلئیک ویروس در مراکز مشخص. اسید نوکلئیک ویروس در داخل پروتئین محافظ جایگرفته و کار تکمیل شدن ویروس روند مختص به خود را پیش میگیرد. تکمیل شدن ویروسها به طور عمومی یکسان نبوده و به طور خصوصی انجام میگیرد. تکمیل شدن ویروسها ی غلافدار یا بدون غلاف و آنانکه دارای ساختمان پیچیده (کمپلکس) هستند و یا دارای نوکلئوکاپسید فنری (هلیکال) اند کاملا متفاوت از هم بوده و هر کدام سیر تکاملی دیگری طی کردهاند. بطور خلاصه میتوان گفت که ویروسهای کروی یا بعبارت دیگر با کاپسید ایکوزاهدرون با بهم پیوستن کاپسومرها و جای گرفتن اسید نوکلئیک در داخل آن کامل میشوند.. ویروسهائی که نوکلئوکاپسید فنری دارند قبلا به روی اسید نوکلئیک پوششی از کاپسومرها قرار گرفته و فرم فنری خود را هنگامی بدست میآورند که ویروس برای خروج از سلول آماده میشود. ویروسهائی که دارای ساختمان پیچیده کمپلکس هستند تکمیل شدنشان بسادگی دیگر ویروسها نبوده و بطوریکه بررسیها نشان میدهند اسید نوکلئیک و پروتئین حافظ و فیلامانهای سطح خارجی آنها و لیپیدی که در ساختمانشان بکار میرود بطور کلی در محل دیگری سنتز شده و ویروس در همان محل فرم میگیرد و کامل میشود غلاف ویروسهای غلافدار، آنهائیکه در داخل هسته سلول تکثیر میشوند پس از خروج از هسته و آنهائیکه در سیتوپلاسم سلول تکمیل میشود هنگام خروج غلافی از غشاء سیتوپلاسمی بدورشان پیچیده شده تکمیل میگردند.
خروج ویروس از سلول[ویرایش]
در مورد خروج ویروسها از سلول دو روش مشاهده میگردد. در بعضی موارد ویروس پس از اینکه تکمیل شد بسته به نوع آن و نوع سلول، با متلاشی شدن سلول میزبان، ویروس آزاد میشود. در اینگونه موارد، پس از انهدام سلول مقدار زیادی ویروس ناگهان آزاد میشود. در بعضی موارد د یگر ویروس بدون اینکه سلول منهدم شود به خارج از سلول رها میگردد. دراین موارد گاهی ویروس همانند جوانهای از سلول جدا میشود. در مورد ویروسهای غلافدار همزمان غلافشان به دورشان پیچیده شده واز سلول بخارج راه میابند.
ژنتیک ویروسهای انسانی و حیوانی تاکنون بطور کامل شناخته نشدهاست. علت اصلی این امر فقدان ساختمان سلولی و متابولیسم اختصاصی آنهاست. چون تکثیرشان کاملا وابسته و گره خورده به سلول میزبان است، بررسی جزء به جزء آن دشوار و مراحل مختلف آن به سختی قابل پیگیری میباشد. از طرفی ویروسها از نظر ژنتیکی استوارتر از باکتریها بوده و تغییرات ژنتیکی در آنها به غیر از ویروسهای آنفولانزا و ایدز در سایر ویروسهای انسانی و حیوانی خیلی بندرت اتفاق میافتد و به دست آوردن موتانتها و یا رکمبینانتهای نوین بسیار مشکل است. از اینرو بررسی ژنتیک آنها بسادگی امکانپذیر نیست و دشواری آن در درمان بیماریهای ویروسی منعکس میگردد.
تغییرات دو جانبه ژنتیکی ویروسها[ویرایش]
تغییرات دو جانبه ژنوم ویروسها هنگامی به وقوع میپیوندند که ژنوم دو ویروس فعال همزمان به داخل سلولی راه یافته وآنرا عفونی نموده، سلول میزبان عمل تکثیر را در مورد هرد و با انجام رسانیده باشد. در اینگونه موارد احتمال تغییرات و تعویض دو جانبه ژنتیکی در میان دو ویروس بسیار زیاد است که در این موارد قسمتی از اسید نوکلئیک ویروس اول به اسید نوکلئیک ویروس دیگر پیوسته اجبارا و ژنهای جدیدی را همرا آورده به ژنهای اولیه اضافه میکند. در صورتیکه قسمتی از اسید نوکلئیک ویروس اول به اسید نوکلئیک ویروس دوم پیوسته و قسمتی از اسید نوکلئیک ویروس دوم به اسید نوکلئیک ویروس اول بپیوندد در این حالت ژنوم هر کدام قسمتی از دست میدهد و قسمتی دیگر به دست میآورد.
بطور کلی در اینگونه موارد میتوان احتمالات زیر را مشاهده نمود:
نوترکیبی، تعویض ترمیمی متقابل قسمتهائی از ژنوم دو ویروس فعال است که همزمان بداخل سلولی راه یافته وآنرا عفونی نموده باشند. تعویض اتفاقی قسمتی از ژنوم دو ویروس فعال گاهی سبب افزایش ویرولانس یا کاهش آن و احتمالا تغییراتی در آنتی ژنهای ویروس بعمل میآید. زمانی حاصل آن بدست آوردن خصوصیات جدیدیست که ویروس تا بحال فاقد آن بوده وبا کسب آن بکلی تغییر ماهییت بدهد. رکمبیناسیون در ویروسهای آبله و آنفولانزا و فلج اطفال و باکتروفاژها گزارش شدهاست
فعال شدن متقاطع[ویرایش]
تلاقی ژنوم ویروس فعالی با ژنوم ویروس غیر فعالی که همزمان بداخل سلولی راه یافته وآنرا عفونی نموده باشند گاهی منجر به تعویض متقاطع قسمتی از ژنوم آنها شده و هرد و ویروس حاصل این تغییرات خصوصیات جدیدی را کسب کرده و درنتیجه هر دو ویروس پدیدارو فعال میگردند. برای مثال جهت تهیه واکسن از ویروسیهایی که در سلولهای معینی قابل تکثیر نیستد میتوان آنها را به کمک این تغییرات ژنتیکی برای تکثیرشان در سلولهای مورد نظر فعال نمود.
دوباره فعال شدن افزایشی[ویرایش]
دو ویروس غیر فعال به سلولی راه میابند و اسید نوکلئیک غیر فعال آن دو به تعمیر و ترمیم یکدیگر پرداخته در نتیجه یک ویروس فعال و دارای خصوصیات هر دو بوجود میآید. این امر و افزایش ژنتیکی متقابل که در این صورت اتفاق میافتد احتمال اویروسی فعال و خشن حاصل میگردد.
تغییرات دو جانبه غیر ژنتیکی[ویرایش]
هنگامی دو ویروس همزمان به سلولی راه یابند و تکثیر شوند، اگر اطلاعات ژنتیکی ویروس اولی (ژنوتیپ) در کاپسید (فنوتیپ) ویروس دومی جایگزین شود اختلاط فنوتیپیک رخ میدهد. این امر موجب پیدایش دو ویروس جدید که بطور اتفاقی فنوتیپ و ژنوتیپ انها تغییر یافته میگردد. این حالت پایدار نبوده، در صورتیکه هر کدام سلولی را عفونی سازند ویروسهای نوزاد فنوتیپ عاریه را از دست داده فنوتیپ اصلی خود را عیان خواهند نمود.
گاهی عفونت همزمان سلول با دو ویروس مختلف منجر به اختلاط ژنوتیپ آنها میگردد. بنابراین درصورتی که که یک ویروس از نظر ژنتیکی اطلاعات کامل دو ویروس مختلف را در بر داشته رد یعنی دو ژنوم مختلف در کاپسیدش جای گرفته باشند از اختلاط ژنوتیپ سخن میگوییم. در این گونه موارد نیز، ثبات ژنتیکی وجود ندارد. حاصل اولین تکثیر آن ویروس منجر به پدیدار شدن دو ویروس مختلف خواهند بود. این پدیده در ویروسهای پارامیکسو گزارش شدهاست
تجربه نشان میدهد، گاهی کشت مای سلولی پس از عفونی شدن بوسیله ویروسی در قبال عفونت با ویروسهای دیگری نوعی مصونیت نشان میدهند. حتی اگر ویروس دیگری بداخل سلول نفوذ کند به تکثیر نمیشود. علت آن به احتمال زیاد ترشح انترفرون سلولی یا کنترل و هدایت متابولیسم سلول توسط ویروس عفونت زا و عدم امکان برای کنترل و هدایت سلول توسط ویروس دوم میباشد. عکس عمل انتر فرانس نیز امکانپذیر است. در این صورت سلولهای عفونی شده توسط ویروس یکم تکثیر ویروس دوم را تشدید و افزایش میدهند. احتمالا علت این امر جلوگیری از ترشح انترفرون به کمک اطلاعات ژنتیکی ویروس دوم است. عکس انتر فرانس امکان دیگریست که با همکاری دو ویروس در جلوگیری از ادامه متابولیسم سلول نتیجه به نفع هردوویروس بوده مراحل تکثیر تکثیرهرد و ویروس ممکن میسازد. گاهی هنگامیکه دو ویروس ناکامل و ناقص سلولی را عفونی میکنند، گرچه هیچکدام به تنهائی امکان را نداشته و احتمال تکثیرشان بسیار ناچیز است، اطلاعات ژنتیکی دو ویروس میتوانند مکمل یکدیگر شده وبا مهار و کنترل متابولیسم سلول هر دو آنها به تکثیر رسند.
زیستشناسی دوره پیش دانشگاهی
This article is about the pathogen. For other uses, see Virus (disambiguation).
For a more accessible and less technical introduction to this topic, see Introduction to viruses.
A virus is a small infectious agent that replicates only inside the living cells of other organisms. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants, and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, about 5,000 viruses have been described in detail, although there are millions of different types. Viruses are found in almost every ecosystem on Earth and are the most abundant type of biological entity. The study of viruses is known as virology, a sub-speciality of microbiology.
Virus particles (known as virions) consist of two or three parts: i) the genetic material made from either DNA or RNA, long molecules that carry genetic information; ii) a protein coat that protects these genes; and in some cases iii) an envelope of lipids that surrounds the protein coat when they are outside a cell. The shapes of viruses range from simple helical and icosahedral forms to more complex structures. The average virus is about one one-hundredth the size of the average bacterium. Most viruses are too small to be seen directly with an optical microscope.
The origins of viruses in the evolutionary history of life are unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria. In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity. Viruses are considered by some to be a life form, because they carry genetic material, reproduce, and evolve through natural selection. However they lack key characteristics (such as cell structure) that are generally considered necessary to count as life. Because they possess some but not all such qualities, viruses have been described as "organisms at the edge of life".
Viruses spread in many ways; viruses in plants are often transmitted from plant to plant by insects that feed on plant sap, such as aphids; viruses in animals can be carried by blood-sucking insects. These disease-bearing organisms are known as vectors. Influenza viruses are spread by coughing and sneezing. Norovirus and rotavirus, common causes of viral gastroenteritis, are transmitted by the faecal–oral route and are passed from person to person by contact, entering the body in food or water. HIV is one of several viruses transmitted through sexual contact and by exposure to infected blood. The range of host cells that a virus can infect is called its "host range". This can be narrow or, as when a virus is capable of infecting many species, broad.
Viral infections in animals provoke an immune response that usually eliminates the infecting virus. Immune responses can also be produced by vaccines, which confer an artificially acquired immunity to the specific viral infection. However, some viruses including those that cause AIDS and viral hepatitis evade these immune responses and result in chronic infections. Antibiotics have no effect on viruses, but several antiviral drugs have been developed.
The word is from the Latin virus referring to poison and other noxious substances, first used in English in 1392. Virulent, from Latin virulentus (poisonous), dates to 1400. A meaning of "agent that causes infectious disease" is first recorded in 1728, before the discovery of viruses by Dmitri Ivanovsky in 1892. The English plural is viruses, whereas the Latin word is a mass noun, which has no classically attested plural. The adjective viral dates to 1948. The term virion (plural virions), which dates from 1959, is also used to refer to a single, stable infective viral particle that is released from the cell and is fully capable of infecting other cells of the same type.
Louis Pasteur was unable to find a causative agent for rabies and speculated about a pathogen too small to be detected using a microscope. In 1884, the French microbiologist Charles Chamberland invented a filter (known today as the Chamberland filter or Chamberland-Pasteur filter) with pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them from the solution. In 1892, the Russian biologist Dmitri Ivanovsky used this filter to study what is now known as the tobacco mosaic virus. His experiments showed that crushed leaf extracts from infected tobacco plants remain infectious after filtration. Ivanovsky suggested the infection might be caused by a toxin produced by bacteria, but did not pursue the idea. At the time it was thought that all infectious agents could be retained by filters and grown on a nutrient medium – this was part of the germ theory of disease. In 1898, the Dutch microbiologist Martinus Beijerinck repeated the experiments and became convinced that the filtered solution contained a new form of infectious agent. He observed that the agent multiplied only in cells that were dividing, but as his experiments did not show that it was made of particles, he called it a contagium vivum fluidum (soluble living germ) and re-introduced the word virus. Beijerinck maintained that viruses were liquid in nature, a theory later discredited by Wendell Stanley, who proved they were particulate. In the same year Friedrich Loeffler and Paul Frosch passed the first animal virus – agent of foot-and-mouth disease (aphthovirus) – through a similar filter.
In the early 20th century, the English bacteriologist Frederick Twort discovered a group of viruses that infect bacteria, now called bacteriophages (or commonly phages), and the French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria on agar, would produce areas of dead bacteria. He accurately diluted a suspension of these viruses and discovered that the highest dilutions (lowest virus concentrations), rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the original suspension. Phages were heralded as a potential treatment for diseases such as typhoid and cholera, but their promise was forgotten with the development of penicillin. The study of phages provided insights into the switching on and off of genes, and a useful mechanism for introducing foreign genes into bacteria.
By the end of the 19th century, viruses were defined in terms of their infectivity, their ability to be filtered, and their requirement for living hosts. Viruses had been grown only in plants and animals. In 1906, Ross Granville Harrison invented a method for growing tissue in lymph, and, in 1913, E. Steinhardt, C. Israeli, and R. A. Lambert used this method to grow vaccinia virus in fragments of guinea pig corneal tissue. In 1928, H. B. Maitland and M. C. Maitland grew vaccinia virus in suspensions of minced hens' kidneys. Their method was not widely adopted until the 1950s, when poliovirus was grown on a large scale for vaccine production.
Another breakthrough came in 1931, when the American pathologist Ernest William Goodpasture grew influenza and several other viruses in fertilized chickens' eggs. In 1949, John Franklin Enders, Thomas Weller, and Frederick Robbins grew polio virus in cultured human embryo cells, the first virus to be grown without using solid animal tissue or eggs. This work enabled Jonas Salk to make an effective polio vaccine.
The first images of viruses were obtained upon the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll. In 1935, American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it was mostly made of protein. A short time later, this virus was separated into protein and RNA parts. The tobacco mosaic virus was the first to be crystallised and its structure could therefore be elucidated in detail. The first X-ray diffraction pictures of the crystallised virus were obtained by Bernal and Fankuchen in 1941. On the basis of her pictures, Rosalind Franklin discovered the full structure of the virus in 1955. In the same year, Heinz Fraenkel-Conrat and Robley Williams showed that purified tobacco mosaic virus RNA and its protein coat can assemble by themselves to form functional viruses, suggesting that this simple mechanism was probably the means through which viruses were created within their host cells.
The second half of the 20th century was the golden age of virus discovery and most of the over 2,000 recognised species of animal, plant, and bacterial viruses were discovered during these years. In 1957, equine arterivirus and the cause of Bovine virus diarrhea (a pestivirus) were discovered. In 1963, the hepatitis B virus was discovered by Baruch Blumberg, and in 1965, Howard Temin described the first retrovirus. Reverse transcriptase, the enzyme that retroviruses use to make DNA copies of their RNA, was first described in 1970, independently by Howard Martin Temin and David Baltimore. In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV.
See also: Evolution of viruses
Viruses are found wherever there is life and have probably existed since living cells first evolved. The origin of viruses is unclear because they do not form fossils, so molecular techniques have been used to compare the DNA or RNA of viruses and are a useful means of investigating how they arose. There are three main hypotheses that try to explain the origins of viruses:
In the past, there were problems with all of these hypotheses: the regressive hypothesis did not explain why even the smallest of cellular parasites do not resemble viruses in any way. The escape hypothesis did not explain the complex capsids and other structures on virus particles. The virus-first hypothesis contravened the definition of viruses in that they require host cells. Viruses are now recognised as ancient and as having origins that pre-date the divergence of life into the three domains. This discovery has led modern virologists to reconsider and re-evaluate these three classical hypotheses.
The evidence for an ancestral world of RNA cells and computer analysis of viral and host DNA sequences are giving a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not proved which of these hypotheses is correct. However, it seems unlikely that all currently known viruses have a common ancestor, and viruses have probably arisen numerous times in the past by one or more mechanisms.
Prions are infectious protein molecules that do not contain DNA or RNA. They can cause infections such as scrapie in sheep, bovine spongiform encephalopathy ("mad cow" disease) in cattle, and chronic wasting disease in deer; in humans, prionic diseases include Kuru, Creutzfeldt–Jakob disease, and Gerstmann–Sträussler–Scheinker syndrome. Although prions are fundamentally different from viruses and viroids, their discovery gives credence to the theory that viruses could have evolved from self-replicating molecules.
Opinions differ on whether viruses are a form of life, or organic structures that interact with living organisms. They have been described as "organisms at the edge of life", since they resemble organisms in that they possess genes and evolve by natural selection, and reproduce by creating multiple copies of themselves through self-assembly. Although they have genes, they do not have a cellular structure, which is often seen as the basic unit of life. Viruses do not have their own metabolism, and require a host cell to make new products. They therefore cannot naturally reproduce outside a host cell – although bacterial species such as rickettsia and chlamydia are considered living organisms despite the same limitation. Accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. They differ from autonomous growth of crystals as they inherit genetic mutations while being subject to natural selection. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules.
Viruses display a wide diversity of shapes and sizes, called morphologies. In general, viruses are much smaller than bacteria. Most viruses that have been studied have a diameter between 20 and 300 nanometres. Some filoviruses have a total length of up to 1400 nm; their diameters are only about 80 nm. Most viruses cannot be seen with an optical microscope so scanning and transmission electron microscopes are used to visualise virions. To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals, such as tungsten, that scatter the electrons from regions covered with the stain. When virions are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only.
A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. These are formed from identical protein subunits called capsomeres. Viruses can have a lipid "envelope" derived from the host cell membrane. The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction. Virally coded protein subunits will self-assemble to form a capsid, in general requiring the presence of the virus genome. Complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus structure can be mechanically (physically) probed through atomic force microscopy. In general, there are four main morphological virus types:
The poxviruses are large, complex viruses that have an unusual morphology. The viral genome is associated with proteins within a central disk structure known as a nucleoid. The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole virion is slightly pleiomorphic, ranging from ovoid to brick shape. Mimivirus is one of the largest characterised viruses, with a capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral. In 2011, researchers discovered the largest then known virus in samples of water collected from the ocean floor off the coast of Las Cruces, Chile. Provisionally named Megavirus chilensis, it can be seen with a basic optical microscope. In 2013, the Pandoravirus genus was discovered in Chile and Australia, and has genomes about twice as large as Megavirus and Mimivirus.
Some viruses that infect Archaea have complex structures that are unrelated to any other form of virus, with a wide variety of unusual shapes, ranging from spindle-shaped structures, to viruses that resemble hooked rods, teardrops or even bottles. Other archaeal viruses resemble the tailed bacteriophages, and can have multiple tail structures.
An enormous variety of genomic structures can be seen among viral species; as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, although only about 5,000 of them have been described in detail. A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus, respectively. The vast majority of viruses have RNA genomes. Plant viruses tend to have single-stranded RNA genomes and bacteriophages tend to have double-stranded DNA genomes.
Viral genomes are circular, as in the polyomaviruses, or linear, as in the adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses and certain DNA viruses, the genome is often divided up into separate parts, in which case it is called segmented. For RNA viruses, each segment often codes for only one protein and they are usually found together in one capsid. However, all segments are not required to be in the same virion for the virus to be infectious, as demonstrated by brome mosaic virus and several other plant viruses.
A viral genome, irrespective of nucleic acid type, is almost always either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to a ladder. The virus particles of some virus families, such as those belonging to the Hepadnaviridae, contain a genome that is partially double-stranded and partially single-stranded.
For most viruses with RNA genomes and some with single-stranded DNA genomes, the single strands are said to be either positive-sense (called the plus-strand) or negative-sense (called the minus-strand), depending on if they are complementary to the viral messenger RNA (mRNA). Positive-sense viral RNA is in the same sense as viral mRNA and thus at least a part of it can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. DNA nomenclature for viruses with single-sense genomic ssDNA is similar to RNA nomenclature, in that the coding strand for the viral mRNA is complementary to it (−), and the non-coding strand is a copy of it (+). However, several types of ssDNA and ssRNA viruses have genomes that are ambisense in that transcription can occur off both strands in a double-stranded replicative intermediate. Examples include geminiviruses, which are ssDNA plant viruses and arenaviruses, which are ssRNA viruses of animals.
Genome size varies greatly between species. The smallest viral genomes – the ssDNA circoviruses, family Circoviridae – code for only two proteins and have a genome size of only two kilobases; the largest–the pandoraviruses–have genome sizes of around two megabases which code for about 2500 proteins.
In general, RNA viruses have smaller genome sizes than DNA viruses because of a higher error-rate when replicating, and have a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes – the genome is split into smaller molecules – thus reducing the chance that an error in a single-component genome will incapacitate the entire genome. In contrast, DNA viruses generally have larger genomes because of the high fidelity of their replication enzymes. Single-strand DNA viruses are an exception to this rule, however, as mutation rates for these genomes can approach the extreme of the ssRNA virus case.
Viruses undergo genetic change by several mechanisms. These include a process called antigenic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are "silent" – they do not change the protein that the gene encodes – but others can confer evolutionary advantages such as resistance to antiviral drugs. Antigenic shift occurs when there is a major change in the genome of the virus. This can be a result of recombination or reassortment. When this happens with influenza viruses, pandemics might result. RNA viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection.
Segmented genomes confer evolutionary advantages; different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses or (offspring) that have unique characteristics. This is called reassortment or viral sex.
Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. Recombination is common to both RNA and DNA viruses.
Viral populations do not grow through cell division, because they are acellular. Instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.
The life cycle of viruses differs greatly between species but there are six basic stages in the life cycle of viruses:
Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, HIV infects a limited range of human leucocytes. This is because its surface protein, gp120, specifically interacts with the CD4 molecule – a chemokine receptor – which is most commonly found on the surface of CD4+ T-Cells. This mechanism has evolved to favour those viruses that infect only cells in which they are capable of replication. Attachment to the receptor can induce the viral envelope protein to undergo changes that results in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface proteins that allow the virus to enter.
Penetration follows attachment: Virions enter the host cell through receptor-mediated endocytosis or membrane fusion. This is often called viral entry. The infection of plant and fungal cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose, and fungi one of chitin, so most viruses can get inside these cells only after trauma to the cell wall. However, nearly all plant viruses (such as tobacco mosaic virus) can also move directly from cell to cell, in the form of single-stranded nucleoprotein complexes, through pores called plasmodesmata. Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. However, given that bacterial cell walls are much less thick than plant cell walls due to their much smaller size, some viruses have evolved mechanisms that inject their genome into the bacterial cell across the cell wall, while the viral capsid remains outside.
Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic nucleic acid.
Replication of viruses involves primarily multiplication of the genome. Replication involves synthesis of viral messenger RNA (mRNA) from "early" genes (with exceptions for positive sense RNA viruses), viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by early or regulatory protein expression. This may be followed, for complex viruses with larger genomes, by one or more further rounds of mRNA synthesis: "late" gene expression is, in general, of structural or virion proteins.
Assembly - Following the structure-mediated self-assembly of the virus particles, some modification of the proteins often occurs. In viruses such as HIV, this modification (sometimes called maturation) occurs after the virus has been released from the host cell.
Release - Viruses can be released from the host cell by lysis, a process that kills the cell by bursting its membrane and cell wall if present: This is a feature of many bacterial and some animal viruses. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host's chromosome. The viral genome is then known as a "provirus" or, in the case of bacteriophages a "prophage". Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host; however, at some point, the provirus or prophage may give rise to active virus, which may lyse the host cells. Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal membrane.
The genetic material within virus particles, and the method by which the material is replicated, varies considerably between different types of viruses.
Effects on the host cell
The range of structural and biochemical effects that viruses have on the host cell is extensive. These are called cytopathic effects. Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and apoptosis. Often cell death is caused by cessation of its normal activities because of suppression by virus-specific proteins, not all of which are components of the virus particle.
Some viruses cause no apparent changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection and often function normally. This causes persistent infections and the virus is often dormant for many months or years. This is often the case with herpes viruses. Some viruses, such as Epstein–Barr virus, can cause cells to proliferate without causing malignancy, while others, such as papillomaviruses, are established causes of cancer.
Viruses are by far the most abundant biological entities on Earth and they outnumber all the others put together. They infect all types of cellular life including animals, plants, bacteria and fungi. However, different types of viruses can infect only a limited range of hosts and many are species-specific. Some, such as smallpox virus for example, can infect only one species – in this case humans, and are said to have a narrow host range. Other viruses, such as rabies virus, can infect different species of mammals and are said to have a broad range. The viruses that infect plants are harmless to animals, and most viruses that infect other animals are harmless to humans. The host range of some bacteriophages is limited to a single strain of bacteria and they can be used to trace the source of outbreaks of infections by a method called phage typing.
Main article: Virus classification
Classification seeks to describe the diversity of viruses by naming and grouping them on the basis of similarities. In 1962, André Lwoff, Robert Horne, and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system bases classification on phylum, class, order, family, genus, and species. Viruses were grouped according to their shared properties (not those of their hosts) and the type of nucleic acid forming their genomes. Later the International Committee on Taxonomy of Viruses was formed. However, viruses are not classified on the basis of phylum or class, as their small genome size and high rate of mutation makes it difficult to determine their ancestry beyond Order. As such, the Baltimore Classification is used to supplement the more traditional hierarchy.
The International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and wrote guidelines that put a greater weight on certain virus properties to maintain family uniformity. A unified taxonomy (a universal system for classifying viruses) has been established. The 9th lCTV Report defines the concept of the virus species as the lowest taxon (group) in a branching hierarchy of viral taxa. However, at present only a small part of the total diversity of viruses has been studied, with analyses of samples from humans finding that about 20% of the virus sequences recovered have not been seen before, and samples from the environment, such as from seawater and ocean sediments, finding that the large majority of sequences are completely novel.
The general taxonomic structure is as follows:
In the current (2013) ICTV taxonomy, 7 orders have been established, the Caudovirales, Herpesvirales, Ligamenvirales, Mononegavirales, Nidovirales, Picornavirales, and Tymovirales. The committee does not formally distinguish between subspecies, strains, and isolates. In total there are 7 orders, 103 families, 22 subfamilies, 455 genera, about 2,827 species and over 4,000 types yet unclassified.
Main article: Baltimore classification
The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.
The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use reverse transcriptase (RT). In addition, ssRNA viruses may be either sense (+) or antisense (−). This classification places viruses into seven groups:
As an example of viral classification, the chicken pox virus, varicella zoster (VZV), belongs to the order Herpesvirales, family Herpesviridae, subfamily Alphaherpesvirinae, and genus Varicellovirus. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase.
Role in human disease
See also: Viral disease
Examples of common human diseases caused by viruses include the common cold, influenza, chickenpox, and cold sores. Many serious diseases such as Ebola virus disease, AIDS, avian influenza, and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus 6 (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. There is controversy over whether the bornavirus, previously thought to cause neurological diseases in horses, could be responsible for psychiatric illnesses in humans.
Viruses have different mechanisms by which they produce disease in an organism, which depends largely on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die, the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency and is a characteristic of the herpes viruses, including Epstein–Barr virus, which causes glandular fever, and varicella zoster virus, which causes chickenpox and shingles. Most people have been infected with at least one of these types of herpes virus. However, these latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia pestis.
Some viruses can cause lifelong or chronic infections, where the viruses continue to replicate in the body despite the host's defense mechanisms. This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus. In populations with a high proportion of carriers, the disease is said to be endemic.
Viral epidemiology is the branch of medical science that deals with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, which means from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include hepatitis B virus and HIV, where the baby is born already infected with the virus. Another, more rare, example is the varicella zoster virus, which, although causing relatively mild infections in humans, can be fatal to the foetus and newborn baby.
Horizontal transmission is the most common mechanism of spread of viruses in populations. Transmission can occur when: body fluids are exchanged during sexual activity, e.g., HIV; blood is exchanged by contaminated transfusion or needle sharing, e.g., hepatitis C; exchange of saliva by mouth, e.g., Epstein–Barr virus; contaminated food or water is ingested, e.g., norovirus; aerosols containing virions are inhaled, e.g., influenza virus; and insect vectors such as mosquitoes penetrate the skin of a host, e.g., dengue. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e., those not immune), the quality of healthcare and the weather.
Epidemiology is used to break the chain of infection in populations during outbreaks of viral diseases. Control measures are used that are based on knowledge of how the virus is transmitted. It is important to find the source, or sources, of the outbreak and to identify the virus. Once the virus has been identified, the chain of transmission can sometimes be broken by vaccines. When vaccines are not available, sanitation and disinfection can be effective. Often, infected people are isolated from the rest of the community, and those that have been exposed to the virus are placed in quarantine. To control the outbreak of foot-and-mouth disease in cattle in Britain in 2001, thousands of cattle were slaughtered. Most viral infections of humans and other animals have incubation periods during which the infection causes no signs or symptoms. Incubation periods for viral diseases range from a few days to weeks, but are known for most infections. Somewhat overlapping, but mainly following the incubation period, there is a period of communicability — a time when an infected individual or animal is contagious and can infect another person or animal. This, too, is known for many viral infections, and knowledge of the length of both periods is important in the control of outbreaks. When outbreaks cause an unusually high proportion of cases in a population, community, or region, they are called epidemics. If outbreaks spread worldwide, they are called pandemics.
Epidemics and pandemics
For more details on this topic, see List of epidemics.
Native American populations were devastated by contagious diseases, in particular, smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population.
A pandemic is a worldwide epidemic. The 1918 flu pandemic, which lasted until 1919, was a category 5 influenza pandemic caused by an unusually severe and deadly influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or otherwise-weakened patients. Older estimates say it killed 40–50 million people, while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918.
Most researchers believe that HIV originated in sub-Saharan Africa during the 20th century; it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognised on 5 June 1981, making it one of the most destructive epidemics in recorded history. In 2007 there were 2.7 million new HIV infections and 2 million HIV-related deaths.
Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include ebolaviruses and marburgviruses. Marburg virus, first discovered in 1967, attracted widespread press attention in April 2005 for an outbreak in Angola. Ebola Virus Disease has also caused intermittent outbreaks with high mortality rates since 1976 when it was first identified. The worst and most recent one is the West Africa epidemic.
For more details on this topic, see Oncovirus.
Viruses are an established cause of cancer in humans and other species. Viral cancers occur only in a minority of infected persons (or animals). Cancer viruses come from a range of virus families, including both RNA and DNA viruses, and so there is no single type of "oncovirus" (an obsolete term originally used for acutely transforming retroviruses). The development of cancer is determined by a variety of factors such as host immunity and mutations in the host. Viruses accepted to cause human cancers include some genotypes of human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein–Barr virus, Kaposi's sarcoma-associated herpesvirus and human T-lymphotropic virus. The most recently discovered human cancer virus is a polyomavirus (Merkel cell polyomavirus) that causes most cases of a rare form of skin cancer called Merkel cell carcinoma. Hepatitis viruses can develop into a chronic viral infection that leads to liver cancer. Infection by human T-lymphotropic virus can lead to tropical spastic paraparesis and adult T-cell leukemia. Human papillomaviruses are an established cause of cancers of cervix, skin, anus, and penis. Within the Herpesviridae, Kaposi's sarcoma-associated herpesvirus causes Kaposi's sarcoma and body cavity lymphoma, and Epstein–Barr virus causes Burkitt's lymphoma, Hodgkin's lymphoma, B lymphoproliferative disorder, and nasopharyngeal carcinoma. Merkel cell polyomavirus closely related to SV40 and mouse polyomaviruses that have been used as animal models for cancer viruses for over 50 years.
Host defence mechanisms
See also: Immune system
The body's first line of defence against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognise, and respond to, pathogens in a generic way, but, unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host.
RNA interference is an important innate defence against viruses. Many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called a dicer that cuts the RNA into smaller pieces. A biochemical pathway - the RISC complex, is activated, which ensures cell survival by degrading the viral mRNA. Rotaviruses have evolved to avoid this defence mechanism by not uncoating fully inside the cell, and releasing newly produced mRNA through pores in the particle's inner capsid. Their genomic dsRNA remains protected inside the core of the virion.
When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies that bind to the virus and often render it non-infectious. This is called humoral immunity. Two types of antibodies are important. The first, called IgM, is highly effective at neutralizing viruses but is produced by the cells of the immune system only for a few weeks. The second, called IgG, is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past. IgG antibody is measured when tests for immunity are carried out.
Antibodies can continue to be an effective defence mechanism even after viruses have managed to gain entry to the host cell. A protein that is in cells, called TRIM21, can attach to the antibodies on the surface of the virus particle. This primes the subsequent destruction of the virus by the enzymes of the cell's proteosome system.
A second defence of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and, if a T cell recognises a suspicious viral fragment there, the host cell is destroyed by killer T cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation. The production of interferon is an important host defence mechanism. This is a hormone produced by the body when viruses are present. Its role in immunity is complex; it eventually stops the viruses from reproducing by killing the infected cell and its close neighbours.
Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. This is known as "escape mutation" as the viral epitopes escape recognition by the host immune response. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift. Other viruses, called neurotropic viruses, are disseminated by neural spread where the immune system may be unable to reach them.
Prevention and treatment
Because viruses use vital metabolic pathways within host cells to replicate, they are difficult to eliminate without using drugs that cause toxic effects to host cells in general. The most effective medical approaches to viral diseases are vaccinations to provide immunity to infection, and antiviral drugs that selectively interfere with viral replication.
For more details on this topic, see Vaccination.
Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella. Smallpox infections have been eradicated. Vaccines are available to prevent over thirteen viral infections of humans, and more are used to prevent viral infections of animals. Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens). Live vaccines contain weakened forms of the virus, which do not cause the disease but, nonetheless, confer immunity. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity (who are described as immunocompromised), because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. The yellow fever virus vaccine, a live-attenuated strain called 17D, is probably the safest and most effective vaccine ever generated.
For more details on this topic, see Antiviral drug.
Antiviral drugs are often nucleoside analogues (fake DNA building-blocks), which viruses mistakenly incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesised DNA is inactive. This is because these analogues lack the hydroxyl groups, which, along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are aciclovir for Herpes simplex virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a large class of drugs called protease inhibitors that inactivate this enzyme.
Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected for the remainder of their lives. However, there is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. The treatment of chronic carriers of the hepatitis B virus by using a similar strategy using lamivudine has been developed.
Infection in other species
Viruses infect all cellular life and, although viruses occur universally, each cellular species has its own specific range that often infect only that species. Some viruses, called satellites, can replicate only within cells that have already been infected by another virus.
Viruses are important pathogens of livestock. Diseases such as foot-and-mouth disease and bluetongue are caused by viruses. Companion animals such as cats, dogs, and horses, if not vaccinated, are susceptible to serious viral infections. Canine parvovirus is caused by a small DNA virus and infections are often fatal in pups. Like all invertebrates, the honey bee is susceptible to many viral infections. However, most viruses co-exist harmlessly in their host and cause no signs or symptoms of disease.
Main article: Plant virus
There are many types of plant virus, but often they cause only a loss of yield, and it is not economically viable to try to control them. Plant viruses are often spread from plant to plant by organisms, known as vectors. These are normally insects, but some fungi, nematode worms, and single-celled organisms have been shown to be vectors. When control of plant virus infections is considered economical, for perennial fruits, for example, efforts are concentrated on killing the vectors and removing alternate hosts such as weeds. Plant viruses cannot infect humans and other animals because they can reproduce only in living plant cells.
Plants have elaborate and effective defence mechanisms against viruses. One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular virus by triggering localised areas of cell death around the infected cell, which can often be seen with the unaided eye as large spots. This stops the infection from spreading. RNA interference is also an effective defence in plants. When they are infected, plants often produce natural disinfectants that kill viruses, such as salicylic acid, nitric oxide, and reactive oxygen molecules.
Plant virus particles or virus-like particles (VLPs) have applications in both biotechnology and nanotechnology. The capsids of most plant viruses are simple and robust structures and can be produced in large quantities either by the infection of plants or by expression in a variety of heterologous systems. Plant virus particles can be modified genetically and chemically to encapsulate foreign material and can be incorporated into supramolecular structures for use in biotechnology.
Main article: Bacteriophage
Bacteriophages are a common and diverse group of viruses and are the most abundant form of biological entity in aquatic environments – there are up to ten times more of these viruses in the oceans than there are bacteria, reaching levels of 250,000,000 bacteriophages per millilitre of seawater. These viruses infect specific bacteria by binding to surface receptor molecules and then entering the cell. Within a short amount of time, in some cases just minutes, bacterial polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins, which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and, in the case of the T4 phage, in just over twenty minutes after injection over three hundred phages could be released.
The major way bacteria defend themselves from bacteriophages is by producing enzymes that destroy foreign DNA. These enzymes, called restriction endonucleases, cut up the viral DNA that bacteriophages inject into bacterial cells. Bacteria also contain a system that uses CRISPR sequences to retain fragments of the genomes of viruses that the bacteria have come into contact with in the past, which allows them to block the virus's replication through a form of RNA interference. This genetic system provides bacteria with acquired immunity to infection.
Some viruses replicate within archaea: these are double-stranded DNA viruses with unusual and sometimes unique shapes. These viruses have been studied in most detail in the thermophilic archaea, particularly the orders Sulfolobales and Thermoproteales. Defences against these viruses may involve RNA interference from repetitive DNA sequences within archaean genomes that are related to the genes of the viruses.
Role in aquatic ecosystems
Main article: Marine bacteriophage
A teaspoon of seawater contains about one million viruses. Most of these are bacteriophages, which are harmless to plants and animals, and are in fact essential to the regulation of saltwater and freshwater ecosystems. They infect and destroy bacteria in aquatic microbial communities, and are the most important mechanism of recycling carbon in the marine environment. The organic molecules released from the dead bacterial cells stimulate fresh bacterial and algal growth. Viral activity may also contribute to the biological pump, the process whereby carbon is sequestered in the deep ocean.
Microorganisms constitute more than 90% of the biomass in the sea. It is estimated that viruses kill approximately 20% of this biomass each day and that there are 15 times as many viruses in the oceans as there are bacteria and archaea. Viruses are the main agents responsible for the rapid destruction of harmful algal blooms, which often kill other marine life. The number of viruses in the oceans decreases further offshore and deeper into the water, where there are fewer host organisms.
Like any organism, marine mammals are susceptible to viral infections. In 1988 and 2002, thousands of harbor seals were killed in Europe by phocine distemper virus. Many other viruses, including caliciviruses, herpesviruses, adenoviruses and parvoviruses, circulate in marine mammal populations.
Role in evolution
Main article: Horizontal gene transfer
Viruses are an important natural means of transferring genes between different species, which increases genetic diversity and drives evolution. It is thought that viruses played a central role in the early evolution, before the diversification of bacteria, archaea and eukaryotes, at the time of the last universal common ancestor of life on Earth. Viruses are still one of the largest reservoirs of unexplored genetic diversity on Earth.
Life sciences and medicine
Viruses are important to the study of molecular and cell biology as they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about aspects of cell biology. For example, viruses have been useful in the study of genetics and helped our understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology.
Geneticists often use viruses as vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion, virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in gene therapy. Eastern European scientists have used phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, because of the high level of antibiotic resistance now found in some pathogenic bacteria. Expression of heterologous proteins by viruses is the basis of several manufacturing processes that are currently being used for the production of various proteins such as vaccine antigens and antibodies. Industrial processes have been recently developed using viral vectors and a number of pharmaceutical proteins are currently in pre-clinical and clinical trials.
Materials science and nanotechnology
Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine.
Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the Naval Research Laboratory in Washington, D.C., using Cowpea Mosaic Virus (CPMV) particles to amplify signals in DNA microarray based sensors. In this application, the virus particles separate the fluorescent dyes used for signalling to prevent the formation of non-fluorescent dimers that act as quenchers. Another example is the use of CPMV as a nanoscale breadboard for molecular electronics.
Many viruses can be synthesized de novo ("from scratch") and the first synthetic virus was created in 2002. Although somewhat of a misconception, it is not the actual virus that is synthesized, but rather its DNA genome (in case of a DNA virus), or a cDNA copy of its genome (in case of RNA viruses). For many virus families the naked synthetic DNA or RNA (once enzymatically converted back from the synthetic cDNA) is infectious when introduced into a cell. That is, they contain all the necessary information to produce new viruses. This technology is now being used to investigate novel vaccine strategies. The ability to synthesize viruses has far-reaching consequences, since viruses can no longer be regarded as extinct, as long as the information of their genome sequence is known and permissive cells are available. As of March 2014[update], the full-length genome sequences of 3843 different viruses, including smallpox, are publicly available in an online database maintained by the National Institutes of Health.
For more details on this topic, see Biological warfare.
The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponised for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. The smallpox virus devastated numerous societies throughout history before its eradication. There are only two centers in the world that are authorized by the WHO to keep stocks of smallpox virus: the Vector Institute in Russia and the Centers for Disease Control and Prevention in the United States. Fears that it may be used as a weapon may not be totally unfounded. As the vaccine for smallpox sometimes had severe side-effects, it is no longer used routinely in any country. Thus, much of the modern human population has almost no established resistance to smallpox, and would be vulnerable to the virus.