Array ( [0] => {{Short description|Study of viruses}} [1] => {{cs1 config|name-list-style=vanc}} [2] => {{For|the journals|Virology (journal)|Virology Journal}} [3] => [[File:Gamma phage.png|thumb|Gamma phage, an example of virus particles (visualised by electron microscopy)]] [4] => [5] => '''Virology''' is the [[Scientific method|scientific study]] of biological [[virus]]es. It is a subfield of [[microbiology]] that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of [[host (biology)|host]] [[cell (biology)|cells]] for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. [6] => [7] => The identification of the causative agent of [[tobacco mosaic disease]] (TMV) as a novel [[pathogen]] by [[Martinus Beijerinck]] (1898) is now acknowledged as being the [[history of virology|official beginning of the field of virology as a discipline]] distinct from [[bacteriology]]. He realized the source was neither a [[bacterial]] nor a [[fungal]] [[infection]], but something completely different. Beijerinck used the word "virus" to describe the mysterious agent in his '[[contagium vivum fluidum]]' ('contagious living fluid'). [[Rosalind Franklin]] proposed the full structure of the tobacco mosaic virus in 1955. [8] => [9] => One main motivation for the study of viruses is because they cause many infectious diseases of plants and animals.{{cite journal |vauthors=Dolja VV, Koonin EV |title=Common origins and host-dependent diversity of plant and animal viromes |journal=Current Opinion in Virology |volume=1 |issue=5 |pages=322–31 |date=November 2011 |pmid=22408703 |pmc=3293486 |doi=10.1016/j.coviro.2011.09.007 |url=}} The study of the manner in which viruses cause disease is [[viral pathogenesis]]. The degree to which a virus causes disease is its [[virulence]].{{cite journal |vauthors=Novella IS, Presloid JB, Taylor RT |title=RNA replication errors and the evolution of virus pathogenicity and virulence |journal=Current Opinion in Virology |volume=9 |issue= |pages=143–7 |date=December 2014 |pmid=25462446 |doi=10.1016/j.coviro.2014.09.017 |url=}} These fields of study are called [[plant virology]], [[animal virology]] and human or [[medical virology]].{{cite journal|last1=Sales|first1=Reneepearl Kim|last2=Oraño|first2=Joseph|last3=Estanislao|first3=Rafael Deo|last4=Ballesteros|first4=Alfredo Jose|last5=Gomez|first5=Ma. Ida Faye|date=2021-04-29|title=Research priority-setting for human, plant, and animal virology: an online experience for the Virology Institute of the Philippines|journal=Health Research Policy and Systems|volume=19|issue=1|pages=70|doi=10.1186/s12961-021-00723-z|issn=1478-4505|pmc=8082216|pmid=33926472 |doi-access=free }} [10] => [11] => Virology began when there were no methods for propagating or visualizing viruses or specific laboratory tests for viral infections. The methods for separating viral nucleic acids ([[RNA]] and [[DNA]]) and [[protein]]s, which are now the mainstay of virology, did not exist. Now there are many methods for observing the structure and functions of viruses and their component parts. Thousands of different viruses are now known about and virologists often specialize in either the viruses that infect plants, or [[bacteria]] and other [[microorganism]]s, or animals. Viruses that infect humans are now studied by medical virologists. Virology is a broad subject covering biology, health, animal welfare, agriculture and ecology. [12] => [13] => ==History== [14] => {{Main|History of virology|Social history of viruses}} [15] => [[File:Martinus Willem Beijerinck in his laboratory.jpg|thumb|right|alt=An old, bespectacled man wearing a suit and sitting at a bench by a large window. The bench is covered with small bottles and test tubes. On the wall behind him is a large old-fashioned clock below which are four small enclosed shelves on which sit many neatly labelled bottles.|[[Martinus Beijerinck]] in his laboratory in 1921]] [16] => [[Louis Pasteur]] was unable to find a causative agent for [[rabies]] and speculated about a pathogen too small to be detected by microscopes.{{cite journal | vauthors = Bordenave G | title = Louis Pasteur (1822-1895) | journal = Microbes and Infection | volume = 5 | issue = 6 | pages = 553–60 | date = May 2003 | pmid = 12758285 | doi = 10.1016/S1286-4579(03)00075-3 }} In 1884, the French [[microbiologist]] [[Charles Chamberland]] invented the [[Chamberland filter]] (or Pasteur-Chamberland filter) with pores small enough to remove all bacteria from a solution passed through it.Shors pp. 74, 827 In 1892, the Russian biologist [[Dmitri Ivanovsky]] used this filter to study what is now known as the [[tobacco mosaic virus]]: crushed leaf extracts from infected tobacco plants remained infectious even after filtration to remove bacteria. Ivanovsky suggested the infection might be caused by a [[toxin]] produced by bacteria, but he did not pursue the idea.Collier p. 3 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]].Dimmock p. 4 [17] => [18] => In 1898, the Dutch microbiologist [[Martinus Beijerinck]] repeated the experiments and became convinced that the filtered solution contained a new form of infectious agent.Dimmock pp. 4–5 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 reintroduced 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, [[aphthovirus]] (the agent of [[foot-and-mouth disease]]), through a similar filter.{{cite book | vauthors = Fenner F | veditors = Mahy BW, Van Regenmortal MH |title=Desk Encyclopedia of General Virology |edition= 1|publisher=Academic Press |location=Oxford |year=2009 |page = 15|isbn=978-0-12-375146-1}} [19] => [20] => In the early 20th century, the English bacteriologist [[Frederick Twort]] discovered a group of viruses that infect bacteria, now called [[bacteriophages]]Shors p. 827 (or commonly 'phages'), and the French-Canadian microbiologist [[Félix d'Herelle]] described viruses that, when added to bacteria on an [[agar plate]], 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.{{cite journal | vauthors = D'Herelle F | title = On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Herelle, presented by Mr. Roux. 1917 | journal = Research in Microbiology | volume = 158 | issue = 7 | pages = 553–54 | date = September 2007 | pmid = 17855060 | doi = 10.1016/j.resmic.2007.07.005 | doi-access = free }} 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 development of [[Antimicrobial resistance|bacterial resistance to antibiotics]] has renewed interest in the therapeutic use of bacteriophages.{{cite journal | vauthors = Domingo-Calap P, Georgel P, Bahram S | title = Back to the future: bacteriophages as promising therapeutic tools | journal = HLA | volume = 87 | issue = 3 | pages = 133–40 | date = March 2016 | pmid = 26891965 | doi = 10.1111/tan.12742 | s2cid = 29223662 }} [21] => [22] => By the end of the 19th century, viruses were defined in terms of their [[infectivity]], their ability to pass filters, and their requirement for living hosts. Viruses had been grown only in plants and animals. In 1906 [[Ross Granville Harrison]] invented a method for [[tissue culture|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.{{cite journal| vauthors = Steinhardt E, Israeli C, Lambert RA |year = 1913|title = Studies on the cultivation of the virus of vaccinia|journal = The Journal of Infectious Diseases |volume = 13|pages = 294–300|doi = 10.1093/infdis/13.2.294|issue = 2|url = https://zenodo.org/record/1431761}} 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.Collier p. 4 [23] => [24] => Another breakthrough came in 1931 when the American pathologist [[Ernest William Goodpasture]] and [[Alice Miles Woodruff]] grew influenza and several other viruses in fertilised chicken eggs.{{cite journal | vauthors = Goodpasture EW, Woodruff AM, Buddingh GJ | title = The cultivation of vaccine and other viruses in the chorioallantoic membrane of chick embryos | journal = Science | volume = 74 | issue = 1919 | pages = 371–72 | date = October 1931 | pmid = 17810781 | doi = 10.1126/science.74.1919.371 | bibcode = 1931Sci....74..371G }} In 1949, [[John Franklin Enders]], [[Thomas Huckle Weller|Thomas Weller]], and [[Frederick Robbins]] grew poliovirus in cultured cells from aborted human embryonic tissue,{{cite book|author=Thomas Huckle Weller|title=Growing Pathogens in Tissue Cultures: Fifty Years in Academic Tropical Medicine, Pediatrics, and Virology|url=https://books.google.com/books?id=jYbqLuOVJlEC&pg=PA57|year=2004|publisher=Boston Medical Library|isbn=978-0-88135-380-8|page=57}} the first virus to be grown without using solid animal tissue or eggs. This work enabled [[Hilary Koprowski]], and then [[Jonas Salk]], to make an effective [[polio vaccine]].{{cite journal | vauthors = Rosen FS | title = Isolation of poliovirus--John Enders and the Nobel Prize | journal = The New England Journal of Medicine | volume = 351 | issue = 15 | pages = 1481–83 | date = October 2004 | pmid = 15470207 | doi = 10.1056/NEJMp048202 }} [25] => [26] => The first images of viruses were obtained upon the invention of [[electron microscopy]] in 1931 by the German engineers [[Ernst Ruska]] and [[Max Knoll]].{{cite book | title = Nobel Lectures, Physics 1981–1990 | date = 1993 | veditors = Frängsmyr T, Ekspång G | publisher = World Scientific Publishing Co. | location = Singapore | bibcode = 1993nlp..book.....F }} [27] => * In 1887, Buist visualised one of the largest, Vaccinia virus, by optical microscopy after staining it. Vaccinia was not known to be a virus at that time. (Buist J.B. ''Vaccinia and Variola: a study of their life history'' Churchill, London) In 1935, American biochemist and virologist [[Wendell Meredith Stanley]] examined the tobacco mosaic virus and found it was mostly made of protein.{{cite journal | vauthors = Stanley WM, Loring HS | title = The Isolation of Crystalline Tobacco Mosaic Virus Protein From Diseased Tomato Plants | journal = Science | volume = 83 | issue = 2143 | pages = 85 | date = January 1936 | pmid = 17756690 | doi = 10.1126/science.83.2143.85 | bibcode = 1936Sci....83...85S }} A short time later, this virus was separated into protein and RNA parts.{{cite journal | vauthors = Stanley WM, Lauffer MA | title = Disintegration of Tobacco Mosaic Virus in Urea Solutions | journal = Science | volume = 89 | issue = 2311 | pages = 345–47 | date = April 1939 | pmid = 17788438 | doi = 10.1126/science.89.2311.345 | bibcode = 1939Sci....89..345S }} [28] => The tobacco mosaic virus was the first to be [[crystal]]lised 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. Based on her X-ray crystallographic pictures, [[Rosalind Franklin]] discovered the full structure of the virus in 1955.{{cite journal | vauthors = Creager AN, Morgan GJ | title = After the double helix: Rosalind Franklin's research on Tobacco mosaic virus | journal = Isis | volume = 99 | issue = 2 | pages = 239–72 | date = June 2008 | pmid = 18702397 | doi = 10.1086/588626 | s2cid = 25741967 }} 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.Dimmock p. 12 [29] => [30] => The second half of the 20th century was the golden age of virus discovery, and most of the documented species of animal, plant, and bacterial viruses were discovered during these years.{{cite journal | vauthors = Norrby E | s2cid = 10595263 | title = Nobel Prizes and the emerging virus concept | journal = Archives of Virology | volume = 153 | issue = 6 | pages = 1109–23 | year = 2008 | pmid = 18446425 | doi = 10.1007/s00705-008-0088-8 }} In 1957 [[Arterivirus|equine arterivirus]] and the cause of [[Bovine virus diarrhea|bovine virus diarrhoea]] (a [[pestivirus]]) were discovered. In 1963 the [[Hepatitis B|hepatitis B virus]] was discovered by [[Baruch Blumberg]],Collier p. 745 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 by Temin and [[David Baltimore]] independently.{{cite journal | vauthors = Temin HM, Baltimore D | title = RNA-directed DNA synthesis and RNA tumor viruses | journal = Advances in Virus Research | volume = 17 | pages = 129–86 | year = 1972 | pmid = 4348509 | doi = 10.1016/S0065-3527(08)60749-6 | isbn = 9780120398171 }} In 1983 [[Luc Montagnier]]'s team at the [[Pasteur Institute]] in France, first isolated the retrovirus now called HIV.{{cite journal | vauthors = Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L | display-authors = 6 | title = Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS) | journal = Science | volume = 220 | issue = 4599 | pages = 868–71 | date = May 1983 | pmid = 6189183 | doi = 10.1126/science.6189183 | bibcode = 1983Sci...220..868B }} In 1989 [[Michael Houghton (virologist)|Michael Houghton]]'s team at [[Chiron Corporation]] discovered [[hepatitis C]].{{cite journal | vauthors = Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M | title = Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome | journal = Science | volume = 244 | issue = 4902 | pages = 359–62 | date = April 1989 | pmid = 2523562 | doi = 10.1126/science.2523562 | citeseerx = 10.1.1.469.3592 | bibcode = 1989Sci...244..359C }}{{cite journal | vauthors = Houghton M | title = The long and winding road leading to the identification of the hepatitis C virus | journal = Journal of Hepatology | volume = 51 | issue = 5 | pages = 939–48 | date = November 2009 | pmid = 19781804 | doi = 10.1016/j.jhep.2009.08.004 | url = http://www.journal-of-hepatology.eu/article/S0168-8278%2809%2900535-2/fulltext | doi-access = free }} [31] => [32] => ==Detecting viruses== [33] => [[File:Jeol Transmission and scanning EM.jpg|thumb|right|An electron microscope]] [34] => There are several approaches to detecting viruses and these include the detection of virus particles (virions) or their [[antigens]] or nucleic acids and infectivity assays. [35] => [36] => ===Electron microscopy=== [37] => [[File:Gastroenteritis viruses.jpg|right|thumb|Electron micrographs of viruses. A, rotavirus; B, adenovirus; C, norovirus; and D, astrovirus.]] [38] => Viruses were seen for the first time in the 1930s when electron microscopes were invented. These microscopes use beams of [[electron]]s instead of light, which have a much shorter wavelength and can detect objects that cannot be seen using light microscopes. The highest magnification obtainable by electron microscopes is up to 10,000,000 timesPayne S. Methods to Study Viruses. Viruses. 2017;37-52. doi:10.1016/B978-0-12-803109-4.00004-0 whereas for light microscopes it is around 1,500 times.{{cite web|title=Magnification - Microscopy, size and magnification (CCEA) - GCSE Biology (Single Science) Revision - CCEA|url=https://www.bbc.co.uk/bitesize/guides/z3vypbk/revision/3|access-date=2023-01-02|website=BBC Bitesize|language=en-GB}} [39] => [40] => Virologists often use [[negative staining#Transmission electron microscopy|negative staining]] to help visualise viruses. In this procedure, the viruses are suspended in a solution of metal salts such as uranium acetate. The atoms of metal are opaque to electrons and the viruses are seen as suspended in a dark background of metal atoms. This technique has been in use since the 1950s.{{cite journal |vauthors=Brenner S, Horne RW |title=A negative staining method for high resolution electron microscopy of viruses |journal=Biochimica et Biophysica Acta |volume=34 |issue= |pages=103–10 |date=July 1959 |pmid=13804200 |doi=10.1016/0006-3002(59)90237-9}} Many viruses were discovered using this technique and negative staining electron microscopy is still a valuable weapon in a virologist's arsenal.{{cite journal |vauthors=Goldsmith CS, Miller SE |title=Modern uses of electron microscopy for detection of viruses |journal=Clinical Microbiology Reviews |volume=22 |issue=4 |pages=552–63 |date=October 2009 |pmid=19822888 |pmc=2772359 |doi=10.1128/CMR.00027-09}} [41] => [42] => Traditional electron microscopy has disadvantages in that viruses are damaged by drying in the high vacuum inside the electron microscope and the electron beam itself is destructive. In [[cryogenic electron microscopy]] the structure of viruses is preserved by embedding them in an environment of [[vitreous water]].{{cite journal|last1=Tivol|first1=William F.|last2=Briegel|first2=Ariane|last3=Jensen|first3=Grant J.|date=October 2008|title=An Improved Cryogen for Plunge Freezing|journal=Microscopy and Microanalysis|language=en|volume=14|issue=5|pages=375–379|doi=10.1017/S1431927608080781|issn=1431-9276|pmc=3058946|pmid=18793481|bibcode=2008MiMic..14..375T}} This allows the determination of biomolecular structures at near-atomic resolution,{{cite journal | vauthors = Cheng Y, Grigorieff N, Penczek PA, Walz T | title = A primer to single-particle cryo-electron microscopy | journal = Cell | volume = 161 | issue = 3 | pages = 438–449 | date = April 2015 | pmid = 25910204 | pmc = 4409659 | doi = 10.1016/j.cell.2015.03.050 }} and has attracted wide attention to the approach as an alternative to [[X-ray crystallography]] or [[NMR spectroscopy]] for the determination of the structure of viruses.{{cite journal |last1=Stoddart |first1=Charlotte |title=Structural biology: How proteins got their close-up |journal=Knowable Magazine |date=1 March 2022 |doi=10.1146/knowable-022822-1|doi-access=free |url=https://knowablemagazine.org/article/living-world/2022/structural-biology-how-proteins-got-their-closeup |access-date=25 March 2022}} [43] => [[File:Rotavirus Reconstruction.jpg|right|thumb|Cryoelectron micrograph of a rotavirus]] [44] => [45] => ===Growth in cultures=== [46] => Viruses are obligate intracellular parasites and because they only reproduce inside the living cells of a host these cells are needed to grow them in the laboratory. For viruses that infect animals (usually called "animal viruses") cells grown in laboratory [[cell culture]]s are used. In the past, fertile hens' eggs were used and the viruses were grown on the membranes surrounding the embryo. This method is still used in the manufacture of some vaccines. For the viruses that infect bacteria, the [[bacteriophages]], the bacteria growing in test tubes can be used directly. For plant viruses, the natural host plants can be used or, particularly when the infection is not obvious, so-called indicator plants, which show signs of infection more clearly.{{cite journal |vauthors=Liu JZ, Richerson K, Nelson RS |title=Growth conditions for plant virus-host studies |journal=Current Protocols in Microbiology |volume=Chapter 16 |issue= |pages=Unit16A.1 |date=August 2009 |pmid=19653216 |doi=10.1002/9780471729259.mc16a01s14 |s2cid=41236532 |url=}}{{cite journal |vauthors=Valmonte-Cortes GR, Lilly ST, Pearson MN, Higgins CM, MacDiarmid RM |title=The Potential of Molecular Indicators of Plant Virus Infection: Are Plants Able to Tell Us They Are Infected? |journal=Plants |volume=11 |issue=2 |date=January 2022 |page=188 |pmid=35050076 |pmc=8777591 |doi=10.3390/plants11020188 |url=|doi-access=free }} [47] => [[File:CPE rounding.jpg|right|thumb|Cytopathic effect of herpes simplex virus. The infected cells have become round and balloon-like.]] [48] => Viruses that have grown in cell cultures can be indirectly detected by the detrimental effect they have on the host cell. These [[cytopathic effect]]s are often characteristic of the type of virus. For instance, [[herpes simplex virus]]es produce a characteristic "ballooning" of the cells, typically human [[fibroblast]]s. Some viruses, such as [[mumps virus]] cause red blood cells from chickens to firmly attach to the infected cells. This is called "haemadsorption" or "hemadsorption". Some viruses produce localised "lesions" in cell layers called [[Viral plaque|plaques]], which are useful in quantitation assays and in identifying the species of virus by [[plaque forming units|plaque reduction assays]].{{cite book |vauthors=Gauger PC, Vincent AL |chapter=Serum Virus Neutralization Assay for Detection and Quantitation of Serum-Neutralizing Antibodies to Influenza a Virus in Swine |title=Animal Influenza Virus |series=Methods in Molecular Biology |volume=1161 |pages=313–24 |date=2014 |pmid=24899440 |doi=10.1007/978-1-4939-0758-8_26 |isbn=978-1-4939-0757-1 |chapter-url=}}{{cite book |vauthors=Dimitrova K, Mendoza EJ, Mueller N, Wood H |title=Zika Virus |chapter=A Plaque Reduction Neutralization Test for the Detection of ZIKV-Specific Antibodies |series=Methods in Molecular Biology |volume=2142 |pages=59–71 |date=2020 |pmid=32367358 |doi=10.1007/978-1-0716-0581-3_5 |isbn=978-1-0716-0580-6 |s2cid=218504421 |chapter-url=}} [49] => [50] => Viruses growing in cell cultures are used to measure their susceptibility to validated and novel [[antiviral drug]]s.{{cite journal |vauthors=Lampejo T |title=Influenza and antiviral resistance: an overview |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=39 |issue=7 |pages=1201–1208 |date=July 2020 |pmid=32056049 |pmc=7223162 |doi=10.1007/s10096-020-03840-9 |url=}} [51] => [52] => ===Serology=== [53] => Viruses are [[antigens]] that induce the production of [[antibodies]] and these antibodies can be used in laboratories to study viruses. Related viruses often react with each other's antibodies and some viruses can be named based on the antibodies they react with. The use of the antibodies which were once exclusively derived from the serum (blood fluid) of animals is called [[serology]].{{cite journal |vauthors=Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK |title=Diagnostic performance of COVID-19 serology assays |journal=The Malaysian Journal of Pathology |volume=42 |issue=1 |pages=13–21 |date=April 2020 |pmid=32342927 |doi= |url=}} Once an antibody–reaction has taken place in a test, other methods are needed to confirm this. Older methods included [[complement fixation test]]s,{{cite journal |vauthors=Swack NS, Gahan TF, Hausler WJ |title=The present status of the complement fixation test in viral serodiagnosis |journal=Infectious Agents and Disease |volume=1 |issue=4 |pages=219–24 |date=August 1992 |pmid=1365549 |doi= |url=}} [[Hemagglutination assay|hemagglutination inhibition]] and [[Neutralizing antibody|virus neutralisation]].{{cite journal |vauthors=Smith TJ |title=Structural studies on antibody recognition and neutralization of viruses |journal=Current Opinion in Virology |volume=1 |issue=2 |pages=150–6 |date=August 2011 |pmid=21887208 |pmc=3163491 |doi=10.1016/j.coviro.2011.05.020 |url=}} Newer methods use [[ELISA|enzyme immunoassay]]s (EIA).{{cite journal |vauthors=Mahony JB, Petrich A, Smieja M |title=Molecular diagnosis of respiratory virus infections |journal=Critical Reviews in Clinical Laboratory Sciences |volume=48 |issue=5–6 |pages=217–49 |date=2011 |pmid=22185616 |doi=10.3109/10408363.2011.640976 |s2cid=24960083 |url=}} [54] => [55] => In the years before [[Polymerase chain reaction|PCR]] was invented [[immunofluorescence]] was used to quickly confirm viral infections. It is an infectivity assay that is virus species specific because antibodies are used. The antibodies are tagged with a dye that is luminescencent and when using an optical microscope with a modified light source, infected cells glow in the dark.{{cite journal |vauthors=AbuSalah MA, Gan SH, Al-Hatamleh MA, Irekeola AA, Shueb RH, Yean Yean C |title=Recent Advances in Diagnostic Approaches for Epstein-Barr Virus |journal=Pathogens |volume=9 |issue=3 |date=March 2020 |page=226 |pmid=32197545 |pmc=7157745 |doi=10.3390/pathogens9030226 |url=|doi-access=free }} [56] => [57] => ===Polymerase chain reaction (PCR) and other nucleic acid detection methods=== [58] => PCR is a mainstay method for detecting viruses in all species including plants and animals. It works by detecting traces of virus specific RNA or DNA. It is very sensitive and specific, but can be easily compromised by contamination. Most of the tests used in veterinary virology and medical virology are based on PCR or similar methods such as [[transcription mediated amplification]]. When a novel virus emerges, such as the covid coronavirus, a specific test can be devised quickly so long as the viral genome has been sequenced and unique regions of the viral DNA or RNA identified.{{cite journal |vauthors=Zhu H, Zhang H, Xu Y, Laššáková S, Korabečná M, Neužil P |title=PCR past, present and future |journal=BioTechniques |volume=69 |issue=4 |pages=317–325 |date=October 2020 |pmid=32815744 |pmc=7439763 |doi=10.2144/btn-2020-0057 |url=}} The invention of [[microfluidic]] tests as allowed for most of these tests to be automated,{{cite journal |vauthors=Wang X, Hong XZ, Li YW, Li Y, Wang J, Chen P, Liu BF |title=Microfluidics-based strategies for molecular diagnostics of infectious diseases |journal=Military Medical Research |volume=9 |issue=1 |pages=11 |date=March 2022 |pmid=35300739 |pmc=8930194 |doi=10.1186/s40779-022-00374-3 |url= |doi-access=free }} Despite its specificity and sensitivity, PCR has a disadvantage in that it does not differentiate infectious and non-infectious viruses and "tests of cure" have to be delayed for up to 21 days to allow for residual viral nucleic acid to clear from the site of the infection.{{cite journal |vauthors=Benzigar MR, Bhattacharjee R, Baharfar M, Liu G |title=Current methods for diagnosis of human coronaviruses: pros and cons |journal=Analytical and Bioanalytical Chemistry |volume=413 |issue=9 |pages=2311–2330 |date=April 2021 |pmid=33219449 |pmc=7679240 |doi=10.1007/s00216-020-03046-0 |url=}} [59] => [60] => ===Diagnostic tests=== [61] => In laboratories many of the diagnostic test for detecting viruses are nucleic acid amplification methods such as PCR. Some tests detect the viruses or their components as these include electron microscopy and [[ELISA|enzyme-immunoassays]]. The so-called "home" or "self"-testing gadgets are usually [[COVID-19 testing#Antigen tests|lateral flow tests]], which detect the virus using a tagged [[monoclonal antibody]].{{Citation|last1=Burrell|first1=Christopher J.|title=Chapter 10 - Laboratory Diagnosis of Virus Diseases|date=2017-01-01|work=Fenner and White's Medical Virology (Fifth Edition)|pages=135–154|editor-last=Burrell|editor-first=Christopher J.|place=London|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-375156-0.00010-2|isbn=978-0-12-375156-0|pmc=7149825|last2=Howard|first2=Colin R.|last3=Murphy|first3=Frederick A.|editor2-last=Howard|editor2-first=Colin R.|editor3-last=Murphy|editor3-first=Frederick A.}} These are also used in agriculture, food and environmental sciences.{{cite journal |vauthors=Koczula KM, Gallotta A |title=Lateral flow assays |journal=Essays in Biochemistry |volume=60 |issue=1 |pages=111–20 |date=June 2016 |pmid=27365041 |pmc=4986465 |doi=10.1042/EBC20150012 |url=}} [62] => [63] => ==Quantitation and viral loads== [64] => {{main|Virus quantification}} [65] => Counting viruses (quantitation) has always had an important role in virology and has become central to the control of some infections of humans where the [[viral load]] is measured.{{cite journal |vauthors=Lee MJ |title=Quantifying SARS-CoV-2 viral load: current status and future prospects |journal=Expert Review of Molecular Diagnostics |volume=21 |issue=10 |pages=1017–1023 |date=October 2021 |pmid=34369836 |pmc=8425446 |doi=10.1080/14737159.2021.1962709 |url=}} There are two basic methods: those that count the fully infective virus particles, which are called infectivity assays, and those that count all the particles including the defective ones. [66] => [67] => ===Infectivity assays=== [68] => [[File:Plaque assay macro.jpg|thumb|Plaques in cells caused herpes simplex virus. The cells have been fixed and stained blue.]] [69] => [70] => Infectivity assays measure the amount (concentration) of infective viruses in a sample of known volume.{{cite journal |vauthors=Mistry BA, D'Orsogna MR, Chou T |title=The Effects of Statistical Multiplicity of Infection on Virus Quantification and Infectivity Assays |journal=Biophysical Journal |volume=114 |issue=12 |pages=2974–2985 |date=June 2018 |pmid=29925033 |pmc=6026352 |doi=10.1016/j.bpj.2018.05.005 |arxiv=1805.02810 |bibcode=2018BpJ...114.2974M |url=}} For host cells, plants or cultures of bacterial or animal cells are used. Laboratory animals such as mice have also been used particularly in veterinary virology.{{cite journal |vauthors=Kashuba C, Hsu C, Krogstad A, Franklin C |title=Small mammal virology |journal=The Veterinary Clinics of North America. Exotic Animal Practice |volume=8 |issue=1 |pages=107–22 |date=January 2005 |pmid=15585191 |pmc=7110861 |doi=10.1016/j.cvex.2004.09.004 |url=}} These are assays are either quantitative where the results are on a continuous scale or quantal, where an event either occurs or it does not. Quantitative assays give [[absolute value]]s and quantal assays give a statistical probability such as the volume of the test sample needed to ensure 50% of the hosts cells, plants or animals are infected. This is called the median infectious dose or [[Minimal infective dose|ID 50]].{{cite journal |vauthors=Cutler TD, Wang C, Hoff SJ, Kittawornrat A, Zimmerman JJ |title=Median infectious dose (ID50) of porcine reproductive and respiratory syndrome virus isolate MN-184 via aerosol exposure |journal=Veterinary Microbiology |volume=151 |issue=3–4 |pages=229–37 |date=August 2011 |pmid=21474258 |doi=10.1016/j.vetmic.2011.03.003 |url=}} Infective bacteriophages can be counted by seeding them onto "lawns" of bacteria in culture dishes. When at low concentrations, the viruses form holes in the lawn that can be counted. The number of viruses is then expressed as [[plaque forming units]]. For the bacteriophages that reproduce in bacteria that cannot be grown in cultures, viral load assays are used.{{cite journal |vauthors=Moon K, Cho JC |title=Metaviromics coupled with phage-host identification to open the viral "black box" |journal=Journal of Microbiology (Seoul, Korea) |volume=59 |issue=3 |pages=311–323 |date=March 2021 |pmid=33624268 |doi=10.1007/s12275-021-1016-9 |s2cid=232023531 |url=}} [71] => [[File:Virus Infected Cells.jpg|thumb|Immunoflourescence: Cells infected by [[rotavirus]] (top) and uninfected cells (bottom)]] [72] => The focus forming assay (FFA) is a variation of the plaque assay, but instead of relying on cell lysis in order to detect plaque formation, the FFA employs [[immunostaining]] techniques using fluorescently labeled [[antibodies]] specific for a viral [[antigen]] to detect infected host cells and infectious virus particles before an actual plaque is formed. The FFA is particularly useful for quantifying classes of viruses that do not lyse the cell membranes, as these viruses would not be amenable to the plaque assay. Like the plaque assay, host cell monolayers are infected with various dilutions of the virus sample and allowed to incubate for a relatively brief incubation period (e.g., 24–72 hours) under a semisolid overlay medium that restricts the spread of infectious virus, creating localized clusters (foci) of infected cells. Plates are subsequently probed with fluorescently labeled antibodies against a viral antigen, and fluorescence microscopy is used to count and quantify the number of foci. The FFA method typically yields results in less time than plaque or fifty-percent-tissue-culture-infective-dose (TCID50) assays, but it can be more expensive in terms of required reagents and equipment. Assay completion time is also dependent on the size of area that the user is counting. A larger area will require more time but can provide a more accurate representation of the sample. Results of the FFA are expressed as focus forming units per milliliter, or FFU/{{cite journal |vauthors=Salgado EN, Upadhyayula S, Harrison SC |title=Single-Particle Detection of Transcription following Rotavirus Entry |journal=Journal of Virology |volume=91 |issue=18 |pages= |date=September 2017 |pmid=28701394 |pmc=5571246 |doi=10.1128/JVI.00651-17 |url=}} [73] => [74] => ===Viral load assays=== [75] => {{main|Viral load}} [76] => When an assay for measuring the infective virus particle is done (Plaque assay, Focus assay), viral titre often refers to the concentration of infectious viral particles, which is different from the total viral particles. Viral load assays usually count the number of viral genomes present rather than the number of particles and use methods similar to [[Polymerase chain reaction|PCR]].{{cite journal |vauthors=Yokota I, Hattori T, Shane PY, Konno S, Nagasaka A, Takeyabu K, Fujisawa S, Nishida M, Teshima T |title=Equivalent SARS-CoV-2 viral loads by PCR between nasopharyngeal swab and saliva in symptomatic patients |journal=Scientific Reports |volume=11 |issue=1 |pages=4500 |date=February 2021 |pmid=33627730 |pmc=7904914 |doi=10.1038/s41598-021-84059-2 |bibcode=2021NatSR..11.4500Y |url=}} Viral load tests are an important in the control of infections by HIV.{{cite journal |vauthors=Nichols BE, Girdwood SJ, Crompton T, Stewart-Isherwood L, Berrie L, Chimhamhiwa D, Moyo C, Kuehnle J, Stevens W, Rosen S |title=Monitoring viral load for the last mile: what will it cost? |journal=Journal of the International AIDS Society |volume=22 |issue=9 |pages=e25337 |date=September 2019 |pmid=31515967 |pmc=6742838 |doi=10.1002/jia2.25337 |url=}} This versatile method can be used for plant viruses.{{cite journal |vauthors=Shirima RR, Maeda DG, Kanju E, Ceasar G, Tibazarwa FI, Legg JP |title=Absolute quantification of cassava brown streak virus mRNA by real-time qPCR |journal=Journal of Virological Methods |volume=245 |issue= |pages=5–13 |date=July 2017 |pmid=28315718 |pmc=5429390 |doi=10.1016/j.jviromet.2017.03.003 |url=}}{{cite journal |vauthors=Rubio L, Galipienso L, Ferriol I |title=Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution |journal=Frontiers in Plant Science |volume=11 |issue= |pages=1092 |date=2020 |pmid=32765569 |pmc=7380168 |doi=10.3389/fpls.2020.01092 |url=|doi-access=free }} [77] => [78] => ==Molecular biology== [79] => Molecular virology is the study of viruses at the level of nucleic acids and proteins. The methods invented by [[molecular biology|molecular biologists]] have all proven useful in virology. Their small sizes and relatively simple structures make viruses an ideal candidate for study by these techniques. [80] => [81] => ===Purifying viruses and their components=== [82] => [[File:CsCl density gradient centrifugation.jpg|right [83] => |thumb|Caesium chloride (CsCl) solution and two morphological types of [[rotavirus]]. Following centrifugation at 100 g a density gradient forms in the CsCl solution and the virus particles separate according to their densities. The tube is 10 cm tall. The viruses are the two "milky" zones close together.]]For further study, viruses grown in the laboratory need purifying to remove contaminants from the host cells. The methods used often have the advantage of concentrating the viruses, which makes it easier to investigate them. [84] => [85] => ====Centrifugation==== [86] => [[Centrifuge]]s are often used to purify viruses. Low speed centrifuges, i.e. those with a top speed of 10,000 [[revolutions per minute]] (rpm) are not powerful enough to concentrate viruses, but [[ultracentrifuge]]s with a top speed of around 100,000 rpm, are and this difference is used in a method called [[differential centrifugation]]. In this method the larger and heavier contaminants are removed from a virus mixture by low speed centrifugation. The viruses, which are small and light and are left in suspension, are then concentrated by high speed centrifugation.{{cite journal |vauthors=Zhou Y, McNamara RP, Dittmer DP |title=Purification Methods and the Presence of RNA in Virus Particles and Extracellular Vesicles |journal=Viruses |volume=12 |issue=9 |date=August 2020 |page=917 |pmid=32825599 |pmc=7552034 |doi=10.3390/v12090917 |url=|doi-access=free }} [87] => [88] => Following differential centrifugation, virus suspensions often remain contaminated with debris that has the same [[sedimentation coefficient]] and are not removed by the procedure. In these cases a modification of centrifugation, called [[buoyant density centrifugation]], is used. In this method the viruses recovered from differential centrifugation are centrifuged again at very high speed for several hours in dense solutions of sugars or salts that form a density gradient, from low to high, in the tube during the centrifugation. In some cases, preformed gradients are used where solutions of steadily decreasing density are carefully overlaid on each other. Like an object in the [[Dead Sea]], despite the centrifugal force the virus particles cannot sink into solutions that are more dense than they are and they form discrete layers of, often visible, concentrated viruses in the tube. Caesium chloride is often used for these solutions as it is relatively inert but easily self-forms a gradient when centrifuged at high speed in an ultracentrifuge.{{cite journal |vauthors=Beards GM |title=A method for the purification of rotaviruses and adenoviruses from faeces |journal=Journal of Virological Methods |volume=4 |issue=6 |pages=343–52 |date=August 1982 |pmid=6290520 |doi=10.1016/0166-0934(82)90059-3 |url=}} Buoyant density centrifugation can also be used to purify the components of viruses such as their nucleic acids or proteins.{{cite journal |vauthors=Su Q, Sena-Esteves M, Gao G |title=Purification of the Recombinant Adenovirus by Cesium Chloride Gradient Centrifugation |journal=Cold Spring Harbor Protocols |volume=2019 |issue=5 |pages= pdb.prot095547|date=May 2019 |pmid=31043560 |doi=10.1101/pdb.prot095547 |s2cid=143423942 |url=}} [89] => [90] => ====Electrophoresis==== [91] => [[File:Coomassie blue stained gel.png|thumb|right|200px|Polyacrylamide gel electrophoresis of [[rotavirus]] proteins stained with Coomassie blue]] [92] => The separation of molecules based on their electric charge is called [[electrophoresis]]. Viruses and all their components can be separated and purified using this method. This is usually done in a supporting medium such as [[agarose]] and [[polyacrylamide gel]]s. The separated molecules are revealed using stains such as [[Coomassie brilliant blue|coomasie blue]], for proteins, or [[ethidium bromide]] for nucleic acids. In some instances the viral components are rendered radioactive before electrophoresis and are revealed using photographic film in a process known as [[autoradiography]].{{cite journal |vauthors=Klepárník K, Boček P |title=Electrophoresis today and tomorrow: Helping biologists' dreams come true |journal=BioEssays |volume=32 |issue=3 |pages=218–226 |date=March 2010 |pmid=20127703 |doi=10.1002/bies.200900152 |s2cid=41587013 |url=}} [93] => [94] => ===Sequencing of viral genomes=== [95] => {{Main|DNA sequencing}} [96] => As most viruses are too small to be seen by a light microscope, sequencing is one of the main tools in virology to identify and study the virus. Traditional Sanger sequencing and next-generation sequencing (NGS) are used to sequence viruses in basic and clinical research, as well as for the diagnosis of emerging viral infections, molecular epidemiology of viral pathogens, and drug-resistance testing. There are more than 2.3 million unique viral sequences in GenBank. NGS has surpassed traditional Sanger as the most popular approach for generating viral genomes.{{cite journal |last1=Castro |first1=Christina |last2=Marine |first2=Rachel |last3=Ramos |first3=Edward |last4=Ng |first4=Terry Fei Fan |title=The effect of variant interference on de novo assembly for viral deep sequencing |journal=BMC Genomics |pages=421 |doi=10.1186/s12864-020-06801-w |date=22 June 2020 |volume=21 |issue=1 |pmid=32571214 |pmc=7306937 |doi-access=free }} Viral genome sequencing as become a central method in viral [[epidemiology]] and [[virus classification|viral classification]]. [97] => [98] => ===Phylogenetic analysis=== [99] => Data from the sequencing of viral genomes can be used to determine evolutionary relationships and this is called [[phylogenetic analysis]].{{cite journal |vauthors=Cui J, Li F, Shi ZL |title=Origin and evolution of pathogenic coronaviruses |journal=Nature Reviews. Microbiology |volume=17 |issue=3 |pages=181–192 |date=March 2019 |pmid=30531947 |pmc=7097006 |doi=10.1038/s41579-018-0118-9 |url=}} Software, such as [[PHYLIP]], is used to draw [[phylogenetic trees]]. This analysis is also used in studying the spread of viral infections in communities ([[epidemiology]]).Gorbalenya AE, Lauber C. Phylogeny of Viruses. Reference Module in Biomedical Sciences. 2017;B978-0-12-801238-3.95723-4. doi:10.1016/B978-0-12-801238-3.95723-4 [100] => [101] => ===Cloning=== [102] => {{main article|Cloning vector}} [103] => When purified viruses or viral components are needed for diagnostic tests or vaccines, cloning can be used instead of growing the viruses.{{cite journal |vauthors=Koch L |title=A platform for RNA virus cloning |journal=Nature Reviews. Genetics |volume=21 |issue=7 |pages=388 |date=July 2020 |pmid=32404960 |pmc=7220607 |doi=10.1038/s41576-020-0246-8 |url=}} At the start of the [[COVID-19 pandemic]] the availability of the [[severe acute respiratory syndrome coronavirus 2]] RNA sequence enabled tests to be manufactured quickly.{{cite journal |vauthors=Thi Nhu Thao T, Labroussaa F, Ebert N, V'kovski P, Stalder H, Portmann J, Kelly J, Steiner S, Holwerda M, Kratzel A, Gultom M, Schmied K, Laloli L, Hüsser L, Wider M, Pfaender S, Hirt D, Cippà V, Crespo-Pomar S, Schröder S, Muth D, Niemeyer D, Corman VM, Müller MA, Drosten C, Dijkman R, Jores J, Thiel V |title=Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform |journal=Nature |volume=582 |issue=7813 |pages=561–565 |date=June 2020 |pmid=32365353 |doi=10.1038/s41586-020-2294-9 |bibcode=2020Natur.582..561T |s2cid=213516085 |url=|doi-access=free }} There are several proven methods for cloning viruses and their components. Small pieces of DNA called [[cloning vector]]s are often used and the most common ones are laboratory modified [[plasmids]] (small circular molecules of DNA produced by bacteria). The viral nucleic acid, or a part of it, is inserted in the plasmid, which is the copied many times over by bacteria. This [[recombinant DNA]] can then be used to produce viral components without the need for native viruses.{{cite journal |vauthors=Rosano GL, Morales ES, Ceccarelli EA |title=New tools for recombinant protein production in Escherichia coli: A 5-year update |journal=Protein Science |volume=28 |issue=8 |pages=1412–1422 |date=August 2019 |pmid=31219641 |pmc=6635841 |doi=10.1002/pro.3668 |url=}} [104] => [105] => ===Phage virology=== [106] => The viruses that reproduce in bacteria, archaea and fungi are informally called "phages",{{cite journal |vauthors=Pennazio S |title=The origin of phage virology |journal=Rivista di Biologia |volume=99 |issue=1 |pages=103–29 |date=2006 |pmid=16791793 |doi= |url=}} and the ones that infect bacteria – [[bacteriophages]] – in particular are useful in virology and biology in general.{{cite journal |vauthors=Harada LK, Silva EC, Campos WF, Del Fiol FS, Vila M, Dąbrowska K, Krylov VN, Balcão VM |title=Biotechnological applications of bacteriophages: State of the art |journal=Microbiological Research |volume=212-213 |issue= |pages=38–58 |date=2018 |pmid=29853167 |doi=10.1016/j.micres.2018.04.007 |s2cid=46921731 |url=|doi-access=free |hdl=1822/54758 |hdl-access=free }} Bacteriophages were some of the first viruses to be discovered, early in the twentieth century,{{cite journal |vauthors=Stone E, Campbell K, Grant I, McAuliffe O |title=Understanding and Exploiting Phage-Host Interactions |journal=Viruses |volume=11 |issue=6 |date=June 2019 |page=567 |pmid=31216787 |pmc=6630733 |doi=10.3390/v11060567 |url=|doi-access=free }} and because they are relatively easy to grow quickly in laboratories, much of our understanding of viruses originated by studying them. Bacteriophages, long known for their positive effects in the environment, are used in [[phage display]] techniques for screening proteins DNA sequences. They are a powerful tool in molecular biology.{{cite journal |vauthors=Nagano K, Tsutsumi Y |title=Phage Display Technology as a Powerful Platform for Antibody Drug Discovery |journal=Viruses |volume=13 |issue=2 |date=January 2021 |page=178 |pmid=33504115 |pmc=7912188 |doi=10.3390/v13020178 |url=|doi-access=free }} [107] => [108] => ==Genetics== [109] => All viruses have [[gene]]s which are studied using [[genetics]].{{cite journal |vauthors=Ibrahim B, McMahon DP, Hufsky F, Beer M, Deng L, Mercier PL, Palmarini M, Thiel V, Marz M |title=A new era of virus bioinformatics |journal=Virus Research |volume=251 |issue= |pages=86–90 |date=June 2018 |pmid=29751021 |doi=10.1016/j.virusres.2018.05.009 |s2cid=21736957 |url=https://refubium.fu-berlin.de/handle/fub188/26445}} All the techniques used in molecular biology, such as cloning, creating mutations [[RNA silencing]] are used in viral genetics.{{cite book | last1=Bamford | first1=Dennis | last2=Zuckerman | first2=Mark A. | title=Encyclopedia of virology | publication-place=Amsterdam | date=2021 | isbn=978-0-12-814516-6 | oclc=1240584737 | page=}} [110] => [111] => ===Reassortment=== [112] => [113] => [[Reassortment]] is the switching of genes from different parents and it is particularly useful when studying the genetics of viruses that have segmented genomes (fragmented into two or more nucleic acid molecules) such as [[influenza virus]]es and [[rotavirus]]es. The genes that encode properties such as [[serotype]] can be identified in this way.{{cite journal |vauthors=McDonald SM, Nelson MI, Turner PE, Patton JT |title=Reassortment in segmented RNA viruses: mechanisms and outcomes |journal=Nature Reviews. Microbiology |volume=14 |issue=7 |pages=448–60 |date=July 2016 |pmid=27211789 |pmc=5119462 |doi=10.1038/nrmicro.2016.46 |url=}} [114] => [115] => ===Recombination=== [116] => [117] => Often confused with reassortment, recombination is also the mixing of genes but the mechanism differs in that ''stretches'' of DNA or RNA molecules, as opposed to the full molecules, are joined during the RNA or DNA replication cycle. Recombination is not as common as reassortment in nature but it is a powerful tool in laboratories for studying the structure and functions of viral genes.{{cite journal |vauthors=Li J, Arévalo MT, Zeng M |title=Engineering influenza viral vectors |journal=Bioengineered |volume=4 |issue=1 |pages=9–14 |date=2013 |pmid=22922205 |pmc=3566024 |doi=10.4161/bioe.21950 |url=}} [118] => [119] => ===Reverse genetics=== [120] => [121] => [[Reverse genetics]] is a powerful research method in virology.{{cite book |vauthors=Lee CW |chapter=Reverse Genetics of Influenza Virus |title=Animal Influenza Virus |series=Methods in Molecular Biology |volume=1161 |pages=37–50 |date=2014 |pmid=24899418 |doi=10.1007/978-1-4939-0758-8_4 |isbn=978-1-4939-0757-1 |chapter-url=}} In this procedure complementary DNA (cDNA) copies of virus genomes called "infectious clones" are used to produce genetically modified viruses that can be then tested for changes in say, virulence or transmissibility.{{cite journal |vauthors=Li Z, Zhong L, He J, Huang Y, Zhao Y |title=Development and application of reverse genetic technology for the influenza virus |journal=Virus Genes |volume=57 |issue=2 |pages=151–163 |date=April 2021 |pmid=33528730 |pmc=7851324 |doi=10.1007/s11262-020-01822-9 |url=}} [122] => [123] => ==Virus classification== [124] => {{for|how viruses are classified with relation to other living things|Tree of life (biology)}} [125] => {{Main|Virus classification}} [126] => A major branch of virology is [[virus classification]]. It is artificial in that it is not based on evolutionary [[phylogenetics]] but it is based shared or distinguishing properties of viruses.{{cite journal |vauthors=Hull R, Rima B |title=Virus taxonomy and classification: naming of virus species |journal=Archives of Virology |volume=165 |issue=11 |pages=2733–2736 |date=November 2020 |pmid=32740831 |doi=10.1007/s00705-020-04748-7 |s2cid=220907379 |url=|doi-access=free }}{{cite book |vauthors=Pellett PE, Mitra S, Holland TC |title=Neurovirology |chapter=Basics of virology |series=Handbook of Clinical Neurology |volume=123 |pages=45–66 |date=2014 |pmid=25015480 |pmc=7152233 |doi=10.1016/B978-0-444-53488-0.00002-X |isbn=9780444534880 |chapter-url=}} It seeks to describe the diversity of viruses by naming and grouping them on the basis of similarities.{{cite journal |vauthors=Simmonds P, Aiewsakun P |title=Virus classification - where do you draw the line? |journal=Archives of Virology |volume=163 |issue=8 |pages=2037–2046 |date=August 2018 |pmid=30039318 |pmc=6096723 |doi=10.1007/s00705-018-3938-z |url=}} In 1962, [[André Lwoff]], [[Robert Horne (virologist)|Robert Horne]], and Paul Tournier were the first to develop a means of virus classification, based on the [[Linnaean taxonomy|Linnaean]] hierarchical system.{{cite journal | vauthors = Lwoff A, Horne RW, Tournier P | title = [A virus system] | language = fr | journal = Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences | volume = 254 | pages = 4225–27 | date = June 1962 | pmid = 14467544 }} This system based classification on [[phylum]], [[class (biology)|class]], [[order (biology)|order]], [[family (biology)|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.{{cite journal | vauthors = Lwoff A, Horne R, Tournier P | title = A system of viruses | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 27 | pages = 51–55 | year = 1962 | pmid = 13931895 | doi = 10.1101/sqb.1962.027.001.008 }} In 1966, the [[International Committee on Taxonomy of Viruses]] (ICTV) was formed. The system proposed by Lwoff, Horne and Tournier was initially not accepted by the ICTV because the small genome size of viruses and their high rate of mutation made it difficult to determine their ancestry beyond order. As such, the [[Baltimore classification]] system has come to be used to supplement the more traditional hierarchy.{{cite journal | vauthors = Fauquet CM, Fargette D | title = International Committee on Taxonomy of Viruses and the 3,142 unassigned species | journal = Virology Journal | volume = 2 | pages = 64 | date = August 2005 | pmid = 16105179 | pmc = 1208960 | doi = 10.1186/1743-422X-2-64 | doi-access = free }} Starting in 2018, the ICTV began to acknowledge deeper evolutionary relationships between viruses that have been discovered over time and adopted a 15-rank classification system ranging from realm to species.{{cite journal|author=International Committee on Taxonomy of Viruses Executive Committee|date=May 2020|title=The New Scope of Virus Taxonomy: Partitioning the Virosphere Into 15 Hierarchical Ranks|journal=Nat Microbiol|volume=5|issue=5|pages=668–674|doi=10.1038/s41564-020-0709-x|pmc=7186216|pmid=32341570}} Additionally, some species within the same genus are grouped into a ''genogroup''.{{cite journal |vauthors=Khan MK, Alam MM |title=Norovirus Gastroenteritis Outbreaks, Genomic Diversity and Evolution: An Overview |journal=Mymensingh Medical Journal|volume=30 |issue=3 |pages=863–873 |date=July 2021 |pmid=34226482 |doi= |url=}}{{cite journal |vauthors=Eberle J, Gürtler L |title=HIV types, groups, subtypes and recombinant forms: errors in replication, selection pressure and quasispecies |journal=Intervirology |volume=55 |issue=2 |pages=79–83 |date=2012 |pmid=22286874 |doi=10.1159/000331993 |s2cid=5642060 |url=|doi-access=free }} [127] => [128] => === ICTV classification === [129] => The 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. Only a small part of the total diversity of viruses has been studied.{{cite journal | vauthors = Delwart EL | title = Viral metagenomics | journal = Reviews in Medical Virology | volume = 17 | issue = 2 | pages = 115–31 | year = 2007 | pmid = 17295196 | doi = 10.1002/rmv.532 | pmc = 7169062 }} As of 2021, 6 realms, 10 kingdoms, 17 phyla, 2 subphyla, 39 classes, 65 orders, 8 suborders, [[List of virus families and subfamilies|233 families, 168 subfamilies]], [[List of virus genera|2,606 genera, 84 subgenera]], and [[List of virus species|10,434 species]] of viruses have been defined by the ICTV.{{cite web|url=https://ictv.global/taxonomy|title=Virus Taxonomy: 2021 Release|website=talk.ictvonline.org|publisher=International Committee on Taxonomy of Viruses|access-date=4 April 2022}} [130] => [131] => The general taxonomic structure of taxon ranges and the suffixes used in taxonomic names are shown hereafter. As of 2021, the ranks of subrealm, subkingdom, and subclass are unused, whereas all other ranks are in use. [132] => [133] => :[[Realm (virology)|Realm]] (''-viria'') [134] => ::Subrealm (''-vira'') [135] => :::[[Kingdom (biology)|Kingdom]] (''-virae'') [136] => ::::Subkingdom (''-virites'') [137] => :::::[[Phylum (biology)|Phylum]] (''-viricota'') [138] => ::::::Subphylum (''-viricotina'') [139] => :::::::[[Class (biology)|Class]] (''-viricetes'') [140] => ::::::::Subclass (''-viricetidae'') [141] => :::::::::[[Order (biology)|Order]] (''-virales'') [142] => ::::::::::Suborder (''-virineae'') [143] => :::::::::::[[Family (biology)|Family]] (''-viridae'') [144] => ::::::::::::Subfamily (''-virinae'') [145] => :::::::::::::[[Genus]] (''-virus'') [146] => ::::::::::::::Subgenus (''-virus'') [147] => :::::::::::::::[[Species]] [148] => [149] => === Baltimore classification === [150] => {{Main|Baltimore classification}} [151] => [[File:VirusBaltimoreClassification.svg|thumb|upright=1.5|alt=A diagram showing how the Baltimore Classification is based on a virus's DNA or RNA and method of mRNA synthesis|The Baltimore Classification of viruses is based on the method of viral [[mRNA]] synthesis.]] [152] => The Nobel Prize-winning biologist [[David Baltimore]] devised the [[Baltimore classification]] system.{{cite journal |vauthors=Koonin EV, Krupovic M, Agol VI |title=The Baltimore Classification of Viruses 50 Years Later: How Does It Stand in the Light of Virus Evolution? |journal=Microbiology and Molecular Biology Reviews |volume=85 |issue=3 |pages=e0005321 |date=August 2021 |pmid=34259570 |doi=10.1128/MMBR.00053-21 |pmc=8483701 |s2cid=235821748 |url=https://hal-pasteur.archives-ouvertes.fr/pasteur-03698244/file/Koonin2021MMBR_a.pdf}} [153] => [154] => 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 (molecular biology)|sense]] (+) or antisense (−). This classification places viruses into seven groups: [155] => {{Baltimore groups}} [156] => {{Portal|Viruses}} [157] => [158] => ==References== [159] => {{Reflist}} [160] => [161] => === Bibliography === [162] => {{Refbegin}} [163] => * {{cite book | vauthors = Collier L, Balows A, Sussman M | date = 1998 | title = Topley and Wilson's Microbiology and Microbial Infections | edition = Ninth | volume = 1 | series = Virology | veditors = Mahy B, Collier LA | isbn = 0-340-66316-2 }} [164] => * {{cite book | vauthors = Dimmock NJ, Easton AJ, Leppard K | date = 2007 | title = Introduction to Modern Virology | edition = Sixth | publisher = Blackwell Publishing | isbn = 978-1-4051-3645-7 }} [165] => * {{cite book | vauthors = Shors T | date = 2017 | title = Understanding Viruses | publisher = Jones and Bartlett Publishers | isbn = 978-1-284-02592-7}} [166] => {{Refend}} [167] => [168] => ==External links== [169] => *{{Commons category-inline|Virology}} [170] => *{{official website|http://www.ictvonline.org/}} of the International Committee on Taxonomy of Viruses [171] => [172] => {{Biotechnology}} [173] => {{Infectious disease}} [174] => {{Branches of biology}} [175] => {{Authority control}} [176] => [177] => [[Category:Virology| ]] [178] => [[Category:Viruses]] [] => )
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Virology

Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy.

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