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Virology

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Virology is the scientific study of viruses – submicroscopic, parasitic organisms of genetic material contained in a protein coat – and virus-like agents. It focuses on the following aspects of viruses: their structure, classification and evolution, their ways to infect and exploit 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. Virology is a subfield of microbiology.

Gamma phage, an example of a virus

The identification of the causative agent of tobacco mosaic disease as a novel pathogen by Martinus Beijerinck (1898) is now acknowledged as being the 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’).

Contents

A major branch of virology is virus classification. Viruses can be classified according to the host cell they infect: animal viruses, plant viruses, fungal viruses, and bacteriophages (viruses infecting bacteria, which include the most complex viruses). Another classification uses the geometrical shape of their capsid (often a helix or an icosahedron) or the virus's structure (e.g. presence or absence of a lipid envelope). Viruses range in size from about 30 nm to about 450 nm, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses has been studied by electron microscopy, NMR spectroscopy, and X-ray crystallography.

The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid they use as genetic material and the viral replication method they employ to coax host cells into producing more viruses:

Virologists also study subviral particles, infectious entities notably smaller and simpler than viruses:

  • viroids (naked circular RNA molecules infecting plants),
  • satellites (nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and
  • prions (proteins that can exist in a pathological conformation that induces other prion molecules to assume that same conformation).

Taxa in virology are not necessarily monophyletic, as the evolutionary relationships of the various virus groups remain unclear. Three hypotheses regarding their origin exist:

  1. Viruses arose from non-living matter, separately from yet in parallel to cells, perhaps in the form of self-replicating RNA ribozymes similar to viroids.
  2. Viruses arose by genome reduction from earlier, more competent cellular life forms that became parasites to host cells and subsequently lost most of their functionality; examples of such tiny parasitic prokaryotes are Mycoplasma and Nanoarchaea.
  3. Viruses arose from mobile genetic elements of cells (such as transposons, retrotransposons or plasmids) that became encapsulated in protein capsids, acquired the ability to "break free" from the host cell and infect other cells.

Of particular interest here is mimivirus, a giant virus that infects amoebae and encodes much of the molecular machinery traditionally associated with bacteria. Two possibilities are that it is a simplified version of a parasitic prokaryote or it originated as a simpler virus that acquired genes from its host.

The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of viral evolution.

While viruses reproduce and evolve, they do not engage in metabolism, do not move, and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses.

One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the common cold, influenza, rabies, measles, many forms of diarrhea, hepatitis, Dengue fever, yellow fever, polio, smallpox and AIDS. Herpes simplex causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer's.

Some viruses, known as oncoviruses, contribute to the development of certain forms of cancer. The best-studied example is the association between Human papillomavirus and cervical cancer: almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus. Another example is the association of infection with hepatitis B and hepatitis C viruses and liver cancer.

Some subviral particles also cause disease: the transmissible spongiform encephalopathies, which include Kuru, Creutzfeldt–Jakob disease and bovine spongiform encephalopathy ("mad cow disease"), are caused by prions, hepatitis D is due to a satellite virus.

The study of the manner in which viruses cause disease is viral pathogenesis. The degree to which a virus causes disease is its virulence.

When the immune system of a vertebrate encounters a virus, it may produce specific antibodies which bind to the virus and neutralize its infectivity or mark it for destruction. Antibody presence in blood serum is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA. Vaccinations protect against viral diseases, in part, by eliciting the production of antibodies. Monoclonal antibodies, specific to the virus, are also used for detection, as in fluorescence microscopy.

The second defense of vertebrates against viruses, cell-mediated immunity, 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 recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.

RNA interference, an important cellular mechanism found in plants, animals and many other eukaryotes, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.

Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; some viral infection might even be beneficial to the host. The lethal viral diseases are believed to have resulted from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis). For example, viruses that cause serious influenza in humans probably have pigs or birds as their natural host, and HIV is thought to derive from the benign non-human primate virus SIV.

While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drugs to treat viral diseases is a comparatively recent development. The first such drug was interferon, a substance that is naturally produced when an infection is detected and stimulates other parts of the immune system.

Bacteriophages, the viruses which infect bacteria, can be relatively easily grown as viral plaques on bacterial cultures. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction, and this horizontal gene transfer is one reason why they served as a major research tool in the early development of molecular biology. The genetic code, the function of ribozymes, the first recombinant DNA and early genetic libraries were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective promoters, are commonly used in molecular biology research today.

Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but cell cultures are increasingly employed for this purpose today.

Since some viruses that infect eukaryotes need to transport their genetic material into the host cell's nucleus, they are attractive tools for introducing new genes into the host (known as transformation or transfection). Modified retroviruses are often used for this purpose, as they integrate their genes into the host's chromosomes.

This approach of using viruses as gene vectors is being pursued in the gene therapy of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system.

Phage therapy, the use of bacteriophages to combat bacterial diseases, was a popular research topic before the advent of antibiotics and has recently seen renewed interest.

Oncolytic viruses are viruses that preferably infect cancer cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results.

Main article: DNA sequencing

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. Recently, NGS has surpassed traditional Sanger as the most popular approach for generating viral genomes.

A new application of genetically engineered viruses in nanotechnology was recently described; see the uses of viruses in material science and nanotechnology. For use in mapping neurons see the applications of pseudorabies in neuroscience.

Main article: History of virology
Adolf Mayer in 1875
Martinus Beijerinck in his laboratory in 1921

The word virus appeared in 1599 and originally meant "venom".

A very early form of vaccination known as variolation was developed several thousand years ago in China. It involved the application of materials from smallpox sufferers in order to immunize others. In 1717 Lady Mary Wortley Montagu observed the practice in Istanbul and attempted to popularize it in Britain, but encountered considerable resistance. In 1796 Edward Jenner developed a much safer method, using cowpox to successfully immunize a young boy against smallpox, and this practice was widely adopted. Vaccinations against other viral diseases followed, including the successful rabies vaccination by Louis Pasteur in 1886. The nature of viruses, however, was not clear to these researchers.

In 1892, the Russian biologist Dmitry Ivanovsky used a Chamberland filter to try to isolate the bacteria that caused tobacco mosaic disease. His experiments showed that crushed leaf extracts from infected tobacco plants remained infectious after filtration. Ivanovsky reported a minuscule infectious agent or toxin, capable of passing the filter, may be being produced by a bacterium.

In 1898 Martinus Beijerinck repeated Ivanovski's work but went further and passed the "filterable agent" from plant to plant, found the action undiminished, and concluded it infectious – replicating in the host – and thus not a mere toxin. He called it contagium vivum fluidum. The question of whether the agent was a "living fluid" or a particle was however still open.

In 1903 it was suggested for the first time that transduction by viruses might cause cancer. In 1908 Bang and Ellerman showed that a filterable virus could transmit chicken leukemia, data largely ignored till the 1930s when leukemia became regarded as cancerous. In 1911 Peyton Rous reported the transmission of chicken sarcoma, a solid tumor, with a virus, and thus Rous became "father of tumor virology". The virus was later called Rous sarcoma virus 1 and understood to be a retrovirus. Several other cancer-causing retroviruses have since been described.

The existence of viruses that infect bacteria (bacteriophages) was first recognized by Frederick Twort in 1911, and, independently, by Félix d'Herelle in 1917. As bacteria could be grown easily in culture, this led to an explosion of virology research.

The cause of the devastating Spanish flu pandemic of 1918 was initially unclear. In late 1918, French scientists showed that a "filter-passing virus" could transmit the disease to people and animals, fulfilling Koch's postulates.

In 1926 it was shown that scarlet fever is caused by a bacterium that is infected by a certain bacteriophage.

While plant viruses and bacteriophages can be grown comparatively easily, animal viruses normally require a living host animal, which complicates their study immensely. In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, Max Theiler managed to grow the yellow fever virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today.

Max Delbrück, an important investigator in the area of bacteriophages, described the basic "life cycle" of a virus in 1937: rather than "growing", a virus particle is assembled from its constituent pieces in one step; eventually it leaves the host cell to infect other cells. The Hershey–Chase experiment in 1952 showed that only DNA and not protein enters a bacterial cell upon infection with bacteriophage T2. Transduction of bacteria by bacteriophages was first described in the same year.

In 1949 John F. Enders, Thomas Weller and Frederick Robbins reported growth of poliovirus in cultured human embryonal cells, the first significant example of an animal virus grown outside of animals or chicken eggs. This work aided Jonas Salk in deriving a polio vaccine from deactivated polio viruses; this vaccine was shown to be effective in 1955.

The first virus that could be crystalized and whose structure could, therefore, be elucidated in detail was tobacco mosaic virus (TMV), the virus that had been studied earlier by Ivanovski and Beijerink. In 1935, Wendell Stanley achieved its crystallization for electron microscopy and showed that it remains active even after crystallization. Clear X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, Rosalind Franklin proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA and its capsid (coat) protein can self-assemble into functional virions, suggesting that this assembly mechanism is also used within the host cell, as Delbrück had proposed earlier.

In 1963, the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a hepatitisB vaccine.

In 1965, Howard Temin described the first retrovirus: a virus whose RNA genome was reverse transcribed into complementary DNA (cDNA), then integrated into the host's genome and expressed from that template. The viral enzyme reverse transcriptase, which along with integrase is a distinguishing trait of retroviruses, was first described in 1970, independently by Howard Temin and David Baltimore. The first retrovirus infecting humans was identified by Robert Gallo in 1974. Later[citation needed] it was found that reverse transcriptase is not specific to retroviruses; retrotransposons which code for reverse transcriptase are abundant in the genomes of all eukaryotes. Ten to forty percent of the human genome derives from such retrotransposons.

In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogenes which, when inserted into the host's genome, would cause cancer. Michael Bishop and Harold Varmus showed that the oncogene of Rous sarcoma virus is in fact not specific to the virus but is contained in the genome of healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene that causes cancer.

1976 saw the first recorded outbreak of Ebola virus disease, a highly lethal virally transmitted disease.

In 1977, Frederick Sanger achieved the first complete sequencing of the genome of any organism, the bacteriophage Phi X 174. In the same year, Richard Roberts and Phillip Sharp independently showed that the genes of adenovirus contain introns and therefore require gene splicing. It was later realized that almost all genes of eukaryotes have introns as well.

A worldwide vaccination campaign led by the UN World Health Organization resulted in the eradication of smallpox in 1979.

In 1982, Stanley Prusiner discovered prions and showed that they cause scrapie.

The first cases of AIDS were reported in 1981, and HIV, the retrovirus causing it, was identified in 1983 by Luc Montagnier, Françoise Barré-Sinoussi and Robert Gallo. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Subsequent tremendous research efforts turned HIV into the best studied virus. Human Herpes Virus 8, the cause of Kaposi's sarcoma which is often seen in AIDS patients, was identified in 1994. Several antiretroviral drugs were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries. Treatment that exists for HIV includes a multitude of different drugs collectively termed Highly Active Antiretroviral Therapy (HAART). HAART attacks many different aspects of the HIV virus, effectively reducing its effects below the limit of detection. However, when the administration of HAART is discontinued, HIV will bounce back. This is because HAART does not attack latently infected HIV cells, which can reactivate.[non-primary source needed]

The Hepatitis C virus was identified using novel molecular cloning techniques in 1987, leading to screening tests that dramatically reduced the incidence of post-transfusion hepatitis.

The first attempts at gene therapy involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in humans, beginning in 1989. The first human studies attempted to correct the genetic disease severe combined immunodeficiency (SCID), but clinical success was limited. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-year-old Jesse Gelsinger died in a gene therapy trial. He suffered a severe immune response after having received an adenovirus vector. Success in the gene therapy of two cases of X-linked SCID was reported in 2000.

In 2002 it was reported that poliovirus had been synthetically assembled in the laboratory, representing the first synthetic organism. Assembling the 7741-base genome from scratch, starting with the virus's published RNA sequence, took about two years. In 2003 a faster method was shown to assemble the 5386-base genome of the bacteriophage Phi X 174 in two weeks.

The giant mimivirus, in some sense an intermediate between tiny prokaryotes and ordinary viruses, was described in 2003 and sequenced in 2004.

The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu pandemic in 1918 was reconstructed in 2005. Sequence information was pieced together from preserved tissue samples of flu victims; viable virus was then synthesized from this sequence. The 2009 flu pandemic involved another strain of Influenza A H1N1, commonly known as "swine flu".

By 1985, Harald zur Hausen had shown that two strains of Human papillomavirus (HPV) cause most cases of cervical cancer. Two vaccines protecting against these strains were released in 2006.

In 2006 and 2007 it was reported that introducing a small number of specific transcription factor genes into normal skin cells of mice or humans can turn these cells into pluripotent stem cells, known as induced pluripotent stem cells. The technique uses modified retroviruses to transform the cells; this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host's genome, which can interrupt other genes and potentially causes cancer.

In 2008, Sputnik virophage was described, the first known virophage: it uses the machinery of a helper virus to reproduce and inhibits reproduction of that helper virus. Sputnik reproduces in amoeba infected by mamavirus, a relative of the mimivirus mentioned above and the largest known virus to date.

An endogenous retrovirus (ERV) is a viral element in the genome that was derived from a retrovirus whose genome has been incorporated into the germ-line genome of some organism and is therefore copied with each reproduction of that organism. It is estimated that about 9 percent of the human genome originates from ERVs. In 2015 it was shown that proteins from an ERV are actively expressed in 3-day-old human embryos and appear to play a role in embryonal development and protect embryos from infection by other viruses.

Since the invention of Organ-on-a-chip in 2010s, the engineering approach has found application in the study of many diseases. The approach has also been introduced to virology and chip models are being developed. Examples include the invention of Influenza model by Donald E. Ingber group, the invention of Ebola virus disease model by Alireza Mashaghi group, and the invention of viral hepatitis model by Marcus Dorner group. The organ chip approach will likely replace animal models for human virology.

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Virology
Virology Language Watch Edit For the journals see Virology journal and Virology Journal This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources Virology news newspapers books scholar JSTOR March 2020 Learn how and when to remove this template message Virology is the scientific study of viruses submicroscopic parasitic organisms of genetic material contained in a protein coat 1 2 and virus like agents It focuses on the following aspects of viruses their structure classification and evolution their ways to infect and exploit 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 Virology is a subfield of microbiology Gamma phage an example of a virus The identification of the causative agent of tobacco mosaic disease as a novel pathogen by Martinus Beijerinck 1898 is now acknowledged as being the official beginning of the field of virology as a discipline distinct from bacteriology 3 4 5 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 Contents 1 Virus structure and classification 2 Viral diseases and host defenses 3 Molecular biology research and viral therapy 4 Sequencing of viruses 5 Other uses of viruses 6 History 7 See also 8 References 9 Further reading 10 External linksVirus structure and classification EditA major branch of virology is virus classification Viruses can be classified according to the host cell they infect animal viruses plant viruses fungal viruses and bacteriophages viruses infecting bacteria which include the most complex viruses 6 Another classification uses the geometrical shape of their capsid often a helix or an icosahedron or the virus s structure e g presence or absence of a lipid envelope 7 Viruses range in size from about 30 nm to about 450 nm which means that most of them cannot be seen with light microscopes The shape and structure of viruses has been studied by electron microscopy NMR spectroscopy and X ray crystallography The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid they use as genetic material and the viral replication method they employ to coax host cells into producing more viruses DNA viruses divided into double stranded DNA viruses and single stranded DNA viruses RNA viruses divided into positive sense single stranded RNA viruses negative sense single stranded RNA viruses and the much less common double stranded RNA viruses reverse transcribing viruses double stranded reverse transcribing DNA viruses and single stranded reverse transcribing RNA viruses including retroviruses Virologists also study subviral particles infectious entities notably smaller and simpler than viruses viroids naked circular RNA molecules infecting plants satellites nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction and prions proteins that can exist in a pathological conformation that induces other prion molecules to assume that same conformation 8 Taxa in virology are not necessarily monophyletic as the evolutionary relationships of the various virus groups remain unclear Three hypotheses regarding their origin exist Viruses arose from non living matter separately from yet in parallel to cells perhaps in the form of self replicating RNA ribozymes similar to viroids Viruses arose by genome reduction from earlier more competent cellular life forms that became parasites to host cells and subsequently lost most of their functionality examples of such tiny parasitic prokaryotes are Mycoplasma and Nanoarchaea Viruses arose from mobile genetic elements of cells such as transposons retrotransposons or plasmids that became encapsulated in protein capsids acquired the ability to break free from the host cell and infect other cells Of particular interest here is mimivirus a giant virus that infects amoebae and encodes much of the molecular machinery traditionally associated with bacteria Two possibilities are that it is a simplified version of a parasitic prokaryote or it originated as a simpler virus that acquired genes from its host The evolution of viruses which often occurs in concert with the evolution of their hosts is studied in the field of viral evolution While viruses reproduce and evolve they do not engage in metabolism do not move and depend on a host cell for reproduction The often debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses Viral diseases and host defenses EditOne main motivation for the study of viruses is the fact that they cause many important infectious diseases among them the common cold influenza rabies measles many forms of diarrhea hepatitis Dengue fever yellow fever polio smallpox and AIDS 9 Herpes simplex causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer s 10 Some viruses known as oncoviruses contribute to the development of certain forms of cancer The best studied example is the association between Human papillomavirus and cervical cancer almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus Another example is the association of infection with hepatitis B and hepatitis C viruses and liver cancer Some subviral particles also cause disease the transmissible spongiform encephalopathies which include Kuru Creutzfeldt Jakob disease and bovine spongiform encephalopathy mad cow disease are caused by prions 11 hepatitis D is due to a satellite virus The study of the manner in which viruses cause disease is viral pathogenesis The degree to which a virus causes disease is its virulence When the immune system of a vertebrate encounters a virus it may produce specific antibodies which bind to the virus and neutralize its infectivity or mark it for destruction Antibody presence in blood serum is often used to determine whether a person has been exposed to a given virus in the past with tests such as ELISA Vaccinations protect against viral diseases in part by eliciting the production of antibodies Monoclonal antibodies specific to the virus are also used for detection as in fluorescence microscopy The second defense of vertebrates against viruses cell mediated immunity 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 recognizes a suspicious viral fragment there the host cell is destroyed and the virus specific T cells proliferate This mechanism is jump started by certain vaccinations RNA interference an important cellular mechanism found in plants animals and many other eukaryotes most likely evolved as a defense against viruses An elaborate machinery of interacting enzymes detects double stranded RNA molecules which occur as part of the life cycle of many viruses and then proceeds to destroy all single stranded versions of those detected RNA molecules Every lethal viral disease presents a paradox killing its host is obviously of no benefit to the virus so how and why did it evolve to do so Today it is believed that most viruses are relatively benign in their natural hosts some viral infection might even be beneficial to the host 12 The lethal viral diseases are believed to have resulted from an accidental jump of the virus from a species in which it is benign to a new one that is not accustomed to it see zoonosis For example viruses that cause serious influenza in humans probably have pigs or birds as their natural host and HIV is thought to derive from the benign non human primate virus SIV While it has been possible to prevent certain viral diseases by vaccination for a long time the development of antiviral drugs to treat viral diseases is a comparatively recent development The first such drug was interferon a substance that is naturally produced when an infection is detected and stimulates other parts of the immune system Molecular biology research and viral therapy EditBacteriophages the viruses which infect bacteria can be relatively easily grown as viral plaques on bacterial cultures Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction 13 and this horizontal gene transfer is one reason why they served as a major research tool in the early development of molecular biology The genetic code the function of ribozymes the first recombinant DNA and early genetic libraries were all arrived at using bacteriophages Certain genetic elements derived from viruses such as highly effective promoters are commonly used in molecular biology research today Growing animal viruses outside of the living host animal is more difficult Classically fertilized chicken eggs have often been used but cell cultures are increasingly employed for this purpose today Since some viruses that infect eukaryotes need to transport their genetic material into the host cell s nucleus they are attractive tools for introducing new genes into the host known as transformation or transfection Modified retroviruses are often used for this purpose as they integrate their genes into the host s chromosomes This approach of using viruses as gene vectors is being pursued in the gene therapy of genetic diseases An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system Phage therapy the use of bacteriophages to combat bacterial diseases was a popular research topic before the advent of antibiotics and has recently seen renewed interest Oncolytic viruses are viruses that preferably infect cancer cells While early efforts to employ these viruses in the therapy of cancer failed there have been reports in 2005 and 2006 of encouraging preliminary results 14 Sequencing of viruses EditMain article DNA sequencing 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 15 Recently NGS has surpassed traditional Sanger as the most popular approach for generating viral genomes 15 Other uses of viruses EditA new application of genetically engineered viruses in nanotechnology was recently described see the uses of viruses in material science and nanotechnology For use in mapping neurons see the applications of pseudorabies in neuroscience History EditMain article History of virology Adolf Mayer in 1875 Dmitri Ivanovsky c 1915 Martinus Beijerinck in his laboratory in 1921 The word virus appeared in 1599 and originally meant venom 16 A very early form of vaccination known as variolation was developed several thousand years ago in China It involved the application of materials from smallpox sufferers in order to immunize others In 1717 Lady Mary Wortley Montagu observed the practice in Istanbul and attempted to popularize it in Britain but encountered considerable resistance In 1796 Edward Jenner developed a much safer method using cowpox to successfully immunize a young boy against smallpox and this practice was widely adopted Vaccinations against other viral diseases followed including the successful rabies vaccination by Louis Pasteur in 1886 The nature of viruses however was not clear to these researchers In 1892 the Russian biologist Dmitry Ivanovsky used a Chamberland filter to try to isolate the bacteria that caused tobacco mosaic disease His experiments showed that crushed leaf extracts from infected tobacco plants remained infectious after filtration Ivanovsky reported a minuscule infectious agent or toxin capable of passing the filter may be being produced by a bacterium 17 18 19 In 1898 Martinus Beijerinck repeated Ivanovski s work but went further and passed the filterable agent from plant to plant found the action undiminished and concluded it infectious replicating in the host and thus not a mere toxin He called it contagium vivum fluidum 20 The question of whether the agent was a living fluid or a particle was however still open In 1903 it was suggested for the first time that transduction by viruses might cause cancer In 1908 Bang and Ellerman showed that a filterable virus could transmit chicken leukemia data largely ignored till the 1930s when leukemia became regarded as cancerous 21 In 1911 Peyton Rous reported the transmission of chicken sarcoma a solid tumor with a virus and thus Rous became father of tumor virology 21 The virus was later called Rous sarcoma virus 1 and understood to be a retrovirus Several other cancer causing retroviruses have since been described The existence of viruses that infect bacteria bacteriophages was first recognized by Frederick Twort in 1911 and independently by Felix d Herelle in 1917 As bacteria could be grown easily in culture this led to an explosion of virology research The cause of the devastating Spanish flu pandemic of 1918 was initially unclear In late 1918 French scientists showed that a filter passing virus could transmit the disease to people and animals fulfilling Koch s postulates 22 In 1926 it was shown that scarlet fever is caused by a bacterium that is infected by a certain bacteriophage While plant viruses and bacteriophages can be grown comparatively easily animal viruses normally require a living host animal which complicates their study immensely In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs a method that is still used today to produce vaccines In 1937 Max Theiler managed to grow the yellow fever virus in chicken eggs and produced a vaccine from an attenuated virus strain this vaccine saved millions of lives and is still being used today Max Delbruck an important investigator in the area of bacteriophages described the basic life cycle of a virus in 1937 rather than growing a virus particle is assembled from its constituent pieces in one step eventually it leaves the host cell to infect other cells The Hershey Chase experiment in 1952 showed that only DNA and not protein enters a bacterial cell upon infection with bacteriophage T2 Transduction of bacteria by bacteriophages was first described in the same year In 1949 John F Enders Thomas Weller and Frederick Robbins reported growth of poliovirus in cultured human embryonal cells the first significant example of an animal virus grown outside of animals or chicken eggs This work aided Jonas Salk in deriving a polio vaccine from deactivated polio viruses this vaccine was shown to be effective in 1955 The first virus that could be crystalized and whose structure could therefore be elucidated in detail was tobacco mosaic virus TMV the virus that had been studied earlier by Ivanovski and Beijerink In 1935 Wendell Stanley achieved its crystallization for electron microscopy and showed that it remains active even after crystallization Clear X ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941 Based on such pictures Rosalind Franklin proposed the full structure of the tobacco mosaic virus in 1955 Also in 1955 Heinz Fraenkel Conrat and Robley Williams showed that purified TMV RNA and its capsid coat protein can self assemble into functional virions suggesting that this assembly mechanism is also used within the host cell as Delbruck had proposed earlier In 1963 the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a hepatitis B vaccine In 1965 Howard Temin described the first retrovirus a virus whose RNA genome was reverse transcribed into complementary DNA cDNA then integrated into the host s genome and expressed from that template The viral enzyme reverse transcriptase which along with integrase is a distinguishing trait of retroviruses was first described in 1970 independently by Howard Temin and David Baltimore The first retrovirus infecting humans was identified by Robert Gallo in 1974 Later citation needed it was found that reverse transcriptase is not specific to retroviruses retrotransposons which code for reverse transcriptase are abundant in the genomes of all eukaryotes Ten to forty percent of the human genome derives from such retrotransposons In 1975 the functioning of oncoviruses was clarified considerably Until that time it was thought that these viruses carried certain genes called oncogenes which when inserted into the host s genome would cause cancer Michael Bishop and Harold Varmus showed that the oncogene of Rous sarcoma virus is in fact not specific to the virus but is contained in the genome of healthy animals of many species The oncovirus can switch this pre existing benign proto oncogene on turning it into a true oncogene that causes cancer 1976 saw the first recorded outbreak of Ebola virus disease a highly lethal virally transmitted disease In 1977 Frederick Sanger achieved the first complete sequencing of the genome of any organism the bacteriophage Phi X 174 In the same year Richard Roberts and Phillip Sharp independently showed that the genes of adenovirus contain introns and therefore require gene splicing It was later realized that almost all genes of eukaryotes have introns as well A worldwide vaccination campaign led by the UN World Health Organization resulted in the eradication of smallpox in 1979 In 1982 Stanley Prusiner discovered prions and showed that they cause scrapie The first cases of AIDS were reported in 1981 and HIV the retrovirus causing it was identified in 1983 by Luc Montagnier Francoise Barre Sinoussi and Robert Gallo 23 24 25 Tests detecting HIV infection by detecting the presence of HIV antibody were developed Subsequent tremendous research efforts turned HIV into the best studied virus Human Herpes Virus 8 the cause of Kaposi s sarcoma which is often seen in AIDS patients was identified in 1994 Several antiretroviral drugs were developed in the late 1990s decreasing AIDS mortality dramatically in developed countries Treatment that exists for HIV includes a multitude of different drugs collectively termed Highly Active Antiretroviral Therapy HAART HAART attacks many different aspects of the HIV virus effectively reducing its effects below the limit of detection However when the administration of HAART is discontinued HIV will bounce back This is because HAART does not attack latently infected HIV cells which can reactivate 26 non primary source needed The Hepatitis C virus was identified using novel molecular cloning techniques in 1987 leading to screening tests that dramatically reduced the incidence of post transfusion hepatitis 27 The first attempts at gene therapy involving viral vectors began in the early 1980s when retroviruses were developed that could insert a foreign gene into the host s genome They contained the foreign gene but did not contain the viral genome and therefore could not reproduce Tests in mice were followed by tests in humans beginning in 1989 The first human studies attempted to correct the genetic disease severe combined immunodeficiency SCID but clinical success was limited In the period from 1990 to 1995 gene therapy was tried on several other diseases and with different viral vectors but it became clear that the initially high expectations were overstated In 1999 a further setback occurred when 18 year old Jesse Gelsinger died in a gene therapy trial He suffered a severe immune response after having received an adenovirus vector Success in the gene therapy of two cases of X linked SCID was reported in 2000 28 In 2002 it was reported that poliovirus had been synthetically assembled in the laboratory representing the first synthetic organism Assembling the 7741 base genome from scratch starting with the virus s published RNA sequence took about two years In 2003 a faster method was shown to assemble the 5386 base genome of the bacteriophage Phi X 174 in two weeks The giant mimivirus in some sense an intermediate between tiny prokaryotes and ordinary viruses was described in 2003 and sequenced in 2004 The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu pandemic in 1918 was reconstructed in 2005 Sequence information was pieced together from preserved tissue samples of flu victims viable virus was then synthesized from this sequence 29 The 2009 flu pandemic involved another strain of Influenza A H1N1 commonly known as swine flu By 1985 Harald zur Hausen had shown that two strains of Human papillomavirus HPV cause most cases of cervical cancer Two vaccines protecting against these strains were released in 2006 In 2006 and 2007 it was reported that introducing a small number of specific transcription factor genes into normal skin cells of mice or humans can turn these cells into pluripotent stem cells known as induced pluripotent stem cells The technique uses modified retroviruses to transform the cells this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host s genome which can interrupt other genes and potentially causes cancer 30 In 2008 Sputnik virophage was described the first known virophage it uses the machinery of a helper virus to reproduce and inhibits reproduction of that helper virus Sputnik reproduces in amoeba infected by mamavirus a relative of the mimivirus mentioned above and the largest known virus to date 31 An endogenous retrovirus ERV is a viral element in the genome that was derived from a retrovirus whose genome has been incorporated into the germ line genome of some organism and is therefore copied with each reproduction of that organism It is estimated that about 9 percent of the human genome originates from ERVs In 2015 it was shown that proteins from an ERV are actively expressed in 3 day old human embryos and appear to play a role in embryonal development and protect embryos from infection by other viruses 32 Since the invention of Organ on a chip in 2010s the engineering approach has found application in the study of many diseases The approach has also been introduced to virology and chip models are being developed Examples include the invention of Influenza model by Donald E Ingber group the invention of Ebola virus disease model by Alireza Mashaghi group and the invention of viral hepatitis model by Marcus Dorner group 33 The organ chip approach will likely replace animal models for human virology See also Edit Viruses portal Animal virology Astrovirology Category Viral diseases Glossary of virology Introduction to viruses List of viral diseases List of viruses Medical microbiology Virus classification Wikipedia WikiProject VirusesReferences Edit Crawford Dorothy 2011 Viruses A Very Short Introduction New York Oxford University Press p 4 ISBN 978 0199574858 Cann Alan 2011 Principles of Molecular Virology 5 ed London Academic Press ISBN 978 0123849397 Scholthof Karen Beth G Shaw John G Zaitlin Milton eds Tobacco Mosaic Virus One Hundred Years of Contributions to Virology St Paul MN American Phytopathological Society Press 1999 Calisher Charles H Horzinek M C eds 100 Years of Virology The Birth and Growth of a Discipline New York Springer 1999 Bos L 2000 100 years of virology from vitalism via molecular biology to genetic engineering Trends in Microbiology 8 2 82 87 Mateu MG 2013 Introduction The Structural Basis of Virus Function Structure and Physics of Viruses Subcellular Biochemistry 68 Nature Public Health Emergency Collection pp 3 51 doi 10 1007 978 94 007 6552 8 1 ISBN 978 94 007 6551 1 PMC 7120296 PMID 23737047 Themes U F O 2017 02 19 6 Viruses Basic Concepts Basicmedical Key Retrieved 2020 05 29 Prion Diseases CDC Archived from the original on 2010 03 04 Retrieved 2016 03 25 Evans Alfred 1982 Viral Infections of Humans New York Plenum Publishing Corporation pp xxv xxxi ISBN 0306406764 Lovheim H Gilthorpe J Adolfsson R Nilsson LG Elgh F July 2014 Reactivated herpes simplex infection increases the risk of Alzheimer s disease Alzheimer s amp Dementia 11 6 593 99 doi 10 1016 j jalz 2014 04 522 PMID 25043910 S2CID 28979698 1 Moved Prion Diseases CDC Archived from the original on 2010 03 04 Retrieved 2017 09 17 Dimmock NJ Easton AJ Leppard K Introduction to Modern Virology Oxford Blackwell Publishers 2007 ch 23 Horizons in human virology subch 23 3 Subtle and insidious virus host interactions sec Virus infections can give their host an evolutionary advantage p 432 Stanley Maloy Horizontal Gene Transfer Retrieved 2016 03 25 Viruses The new cancer hunters IsraCast 1 March 2006 a b Castro Christina Marine Rachel Ramos Edward Ng Terry Fei Fan 22 June 2020 The effect of variant interference on de novo assembly for viral deep sequencing BMC Genomics 21 1 421 doi 10 1186 s12864 020 06801 w PMC 7306937 PMID 32571214 Virus Merriam Webster Inc 2011 Sussman Max Topley W W C Wilson Graham K Collier L H Balows Albert 1998 Topley amp Wilson s microbiology and microbial infections London Arnold p 3 ISBN 0 340 66316 2 Iwanowski D 1892 Uber die Mosaikkrankheit der Tabakspflanze Bulletin Scientifique Publie Par l Academie Imperiale des Sciences de Saint Petersbourg Nouvelle Serie III in German and Russian St Petersburg 35 67 70 Translated into English in Johnson J Ed 1942 Phytopathological classics St Paul Minnesota American Phytopathological Society No 7 pp 27 30 Iwanowski D 1903 Uber die Mosaikkrankheit der Tabakspflanze Zeitschrift fur Pflanzenkrankheiten und Pflanzenschutz in German 13 1 41 Pennazio S 2007 Genetics and virology Two interdisciplinary branches of biology Rivista di Biologia 100 1 119 46 PMID 17592822 a b Van Epps HL 2005 Peyton Rous Father of the tumor virus PDF Journal of Experimental Medicine 201 3 320 doi 10 1084 jem 2013fta PMC 2213042 PMID 15756727 The Medical and Scientific Conceptions of Influenza Human Virology at Stanford Montagnier L 2002 Historical essay A History of HIV Discovery Science 298 5599 1727 28 doi 10 1126 science 1079027 PMID 12459575 S2CID 57481800 Gallo RC 2002 Historical essay The Early Years of HIV AIDS Science 298 5599 1728 30 doi 10 1126 science 1078050 PMID 12459576 S2CID 82899411 Gallo RC Montagnier L 2002 Historical essay Prospects for the Future Science 298 5599 1730 31 doi 10 1126 science 1079864 PMID 12459577 S2CID 34227893 Hu Wenhui Kaminski Rafal Yang Fan Zhang Yonggang Cosentino Laura Li Fang Luo Biao Alvarez Carbonell David Garcia Mesa Yoelvis 2014 08 05 RNA directed gene editing specifically eradicates latent and prevents new HIV 1 infection Proceedings of the National Academy of Sciences 111 31 11461 66 Bibcode 2014PNAS 11111461H doi 10 1073 pnas 1405186111 ISSN 0027 8424 PMC 4128125 PMID 25049410 2000 Albert Lasker Award for Clinical Medical Research Archived October 28 2007 at the Wayback Machine The Lasker Foundation Accessed 20 February 2008 Debyser Zeger 2003 A Short Course on Virology Vectorology Gene Therapy PDF Current Gene Therapy 3 6 495 99 doi 10 2174 1566523034578122 PMID 14683447 Archived from the original PDF on 2008 08 02 Kolata Gina 2005 10 06 Experts Unlock Clues to Spread of 1918 Flu Virus The New York Times ISSN 0362 4331 Retrieved 2008 02 03 Stem Cells This Time without the Cancer Scientific American News 30 November 2007 Biggest Known Virus Yields First Ever Virophage Microbe Magazine November 2008 Archived from the original on July 22 2011 Virus hiding in our genome protects early human embryos New Scientist 20 April 2015 H Tang et al Human Organs on Chips for Virology Trends in Microbiology 2020 Further reading EditBaron Samuel ed 1996 Section 2 Virology Medical Microbiology 4th ed Archived from the original on 2006 03 07 freely searchable online book Coffin Hughes Varmus 1997 Retroviruses Cold Spring Harbor Laboratory Press ISBN 9780879695712 freely searchable online book Villarreal L P 2005 Viruses and the Evolution of Life Washington DC ASM Press ISBN 1 55581 309 7 External links EditICTV International Committee on Taxonomy of Viruses searchable virus taxonomy updated versions in 2007 and 2008 Explanations of the virus species concept and viral taxonomy David Sander All the Virology on the WWW collection of links pictures lecture notes Many of the links on this site are broken and it does not appear to be being maintained Online lectures in virology University of South Carolina Microbes info is a microbiology information portal containing a vast collection of resources including articles news frequently asked questions and links pertaining to the field of microbiology MicrobiologyBytes Origins of Virology MicrobiologyBytes The Virology Time Machine Timeline of the history of virology from the Washington University in St Louis Wong s Virology Vaccine Research Center VRC Information concerning vaccine research studies This Week in Virology Podcast by Vincent Racaniello 1 Virulogy Ton E van den Bogaard University Maastricht the Netherlands 2 Retrieved from https en wikipedia org w index php title Virology amp oldid 1046602467, wikipedia, wiki, book,

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