Introduction to viruses

Taxobox | color=violet
name = Viruses

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image_caption = Computer reconstruction of a rotavirus particle
subdivision_ranks = Groups
subdivision = I: dsDNA viruses
II: ssDNA viruses
III: dsRNA viruses
IV: (+)ssRNA viruses
V: (-)ssRNA viruses
VI: ssRNA-RT viruses
VII: dsDNA-RT virusesA virus is a microorganism that reproduces inside the cells of living hosts. When infected by a virus, a cell is forced to make thousands of identical viruses. They reproduce at an extraordinary rate, but the viruses cannot do this alone: their reproduction is entirely dependent on their presence within a host cell. Unlike most living things, viruses do not have cells that divide; new viruses are assembled in the infected host cell. Over 2,000 species of virus have been discovered.

A virus consists of two or three parts: all viruses have genes made from either DNA or RNA, long molecules that carry the genetic information; all have a protein coat that protects these genes; and some have an envelope of fat that surrounds them when they are not within a cell. Viruses vary in shape from the simple helical and icosahedral to more complex structures. Viruses are about 100 times smaller than bacteria, and it would take 30,000 to 750,000 of them, side by side, to stretch to convert|1|cm.

Viruses spread in many different ways. Plant viruses are often spread from plant to plant by insects and other organisms, known as "vectors". Some viruses are spread by blood-sucking insects. Each species of virus relies on a different method. Whereas viruses such as influenza are spread through the air by people's coughing and sneezing, others such as norovirus, which are transmitted by the faecal-oral route, contaminate hands, food and water. Rotavirus is often spread by direct contact with infected children. HIV is one of several major viruses that are transmitted during sex. The origins of viruses is unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.

Viral infections often cause disease in humans and animals; they are usually completely eliminated by the immune system, and this confers lifetime immunity to the host for that virus. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections. Vaccines that produce lifelong immunity can prevent some viral infections.

Origins

Viruses are found wherever there is life and have probably existed since living cells first evolved. The origin of viruses is unclear because they do not form fossils, so molecular techniques have been the most useful means of hypothesising how they arose. However, these techniques rely on the availability of ancient viral DNA or RNA, but, unfortunately, most of the viruses that have been preserved and stored in laboratories are less than 90 years old. [Shors. p. 16] [Topley and Wilson pp. 18–19] Molecular methods have only been successful in tracing the ancestry of viruses that evolved in the 20th century. [Liu, Y., Nickle, D.C., Shriner, D., Jensen, M.A., Learn, G.H. Jr, Mittler, J.E., Mullins, J.I. (2004) "Molecular clock-like evolution of human immunodeficiency virus type 1"."Virology". 10;329(1):101-8, PMID 15476878]

There are three main theories of the origins of viruses: [Shors pp. 14–16] [Topley and Wilson pp.11–21]

*Regressive theory: Viruses may have once been small cells that parasitised larger cells. Over time, genes not required by their parasitism were lost. The bacteria rickettsia and chlamydia are living cells that, like viruses, can reproduce only inside host cells. They lend credence to this theory, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. [Topley and Wilson p. 11]

*Cellular origin theory: Some viruses may have evolved from bits of DNA or RNA that "escaped" from the genes of a larger organism. The escaped DNA could have come from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria. [Topley and Wilson pp. 11–12]

*Coevolution theory: Viruses may have evolved from complex molecules of protein and DNA at the same time as cells first appeared on earth and would have been dependent on cellular life for many millions of years.

Discovery

In 1884, the French microbiologist Charles Chamberland invented a filter, (known today as the Chamberland filter or Chamberland-Pasteur filter), that has pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them from the solution. [Shors pp. 76–77] Russian biologist Dimitri Ivanovski used this filter to study what is now known to be the tobacco mosaic virus. His experiments showed that the crushed leaf extracts of infected tobacco plants are still infectious after filtration.

At the same time several other scientists proved that, although these agents (later called "viruses") were different from bacteria, they could still cause disease, and they were about a hundred times smaller than bacteria. In 1899 The Dutch microbiologist Martinus Beijerinck observed that the agent multiplied only in dividing cells. Having failed to demonstrate its particulate nature he called it a "contagium vivum fluidum" to mean "soluble living germ". [Topley and Wilson p. 3] In the early 20th century, English bacteriologist Frederick Twort discovered viruses that infect bacteria, [Shors p. 589] and French-Canadian microbiologist Félix d'Herelle described viruses that, when added to bacteria growing on agar, would lead to the formation of whole areas of dead bacteria. Counting these dead areas allowed him to calculate the number of viruses in the suspension. [D'Herelle, F. "Res. Microbiol." 2007 Sep;158(7):553–4. Epub 2007 Jul 28. "On an invisible microbe antagonistic toward dysenteric bacilli": brief note by Mr. F. D'Herelle, presented by Mr. Roux. 1917. PMID 17855060]

With the invention of electron microscopy in 1931 by the German engineers Ernst Ruska and Max Knoll came the first images of viruses. [From "Nobel Lectures, Physics 1981-1990", (1993) Editor-in-Charge Tore Frängsmyr, Editor Gösta Ekspång, World Scientific Publishing Co., Singapore] In 1935 American biochemist and virologist Wendell Meredith Stanley examined the tobacco mosaic virus and found it to be mostly made from protein. [Stanley, W.M., Loring, H.S., (1936) "The isolation of crystalline tobacco mosaic virus protein from diseased tomato plants" "Science", 83, p.85 PMID 17756690 ] A short time later, this virus was separated into protein and RNA parts. [Stanley, W.M., Lauffer, M.A. (1939) "Disintegration of tobacco mosaic virus in urea solutions" "Science" 89, pp. 345–347 PMID 17788438] A problem for early scientists was that they did not know how to grow viruses without using live animals. The breakthrough came in 1931, when the American pathologist Ernest William Goodpasture grew influenza and several other viruses in fertilised chickens' eggs. [ Goodpasture, E.W., Woodruff, A.M., Buddingh, G.J. (1931) "The cultivation of vaccine and other viruses in the chorioallantoic membrane of chick embryos" "Science" 74, pp. 371–372 PMID 17810781] Some viruses could not be grown in chickens' eggs, but this problem was solved in 1949 when John Franklin Enders, Thomas Huckle Weller and Frederick Chapman Robbins grew polio virus in cultures of living animal cells. [Rosen, F.S.(2004) "Isolation of poliovirus—John Enders and the Nobel Prize" "New England Journal of Medicine", 351,pp. 1481–83 PMID 15470207] Over 2,000 species of virus have been discovered. [ Shors p. 78]

Structure

A virus particle, known as a virion, consists of genes made from DNA or RNA which are surrounded by a protective coat of protein called a capsid.Topley and Wilson pp. 33–55] The capsid is made of many smaller, identical protein molecules which are called capsomers. The arrangement of the capsomers can either be icosahedral (20-sided), helical or more complex. There is an inner shell around the DNA or RNA called the nucleocapsid, which is formed by proteins. Some viruses are surrounded by a bubble of lipid (fat) called an envelope.

Size

Viruses are among the smallest infectious agents, and most of them can only be seen by electron microscopy. Most viruses cannot be seen by light microscopy (in other words, they are sub-microscopic); their sizes range from 20 to 300 nm. They are so small that it would take 30,000 to 750,000 of them, side by side, to stretch to one cm.

Genes

Genes are made from DNA (deoxyribonucleic acid) and, in many viruses, RNA (ribonucleic acid). The biological information contained in an organism is encoded in its DNA or RNA. Most organisms use DNA, but many viruses have RNA as their genetic material. The DNA or RNA of viruses consists of either a single strand or a double helix. [Shors pp. 54–61]

Viruses reproduce rapidly because they have only a few genes compared to humans who have 20,000–25,000. [International Human Genome Sequencing Consortium (2004) "Finishing the euchromatic sequence of the human genome" "Nature" 431, p. 931–945 PMID 15496913] For example, influenza virus has only eight genes and rotavirus has eleven. These genes encode structural proteins that form the virus particle, or non-structural proteins, that are only found in cells infected by the virus. [Shors p. 73]

All cells, and many viruses, produce proteins that are enzymes called DNA polymerase and RNA polymerase which make new copies of DNA and RNA. A virus's polymerase enzymes are often much more efficient at making DNA and RNA than the host cell's. [Shors pp. 32–34 ] However, RNA polymerase enzymes often make mistakes, and this is one of the reasons why RNA viruses often mutate to form new strains. [Shors p. 510 ]

In some species of RNA virus, the genes are not on a continuous molecule of RNA, but are separated. The influenza virus, for example, has eight separate genes made of RNA. When two different strains of influenza virus infect the same cell, these genes can mix and produce new strains of the virus in a process called reassortment. [Shors p. 327]

Protein synthesis

Proteins are essential to life. Cells produce new protein molecules from amino acid building blocks based on information coded in DNA. Each type of protein is a specialist that only performs one function, so if a cell needs to do something new, it must make a new protein. Viruses force the cell to make new proteins that the cell does not need, but are needed for the virus to reproduce. Protein synthesis basically consists of two major steps: transcription and translation.

Transcription is the process where information in DNA, called the genetic code, is used to produce RNA copies called messenger RNA (mRNA). These migrate through the cell and carry the code to ribosomes where it is used to make proteins. This is called translation because the protein's amino acid structure is determined by the mRNA's code.

Some RNA genes of viruses function directly as mRNA without further modification. For this reason, these viruses are called positive-sense RNA viruses. [Topley and Wilson pp. 75–82] In other RNA viruses, the RNA is a complementary copy of mRNA and these viruses rely on the cell's or their own enzyme to make mRNA. These are called negative-sense RNA viruses. In viruses made from DNA, the method of mRNA production is similar to that of the cell. The species of viruses called retroviruses behave completely differently: they have RNA, but inside the host cell a DNA copy of their RNA is made. This DNA is then incorporated into the host's, and copied into mRNA by the cell's normal pathways. [Shors pp. 248–250 ]

Life-cycle

When a virus infects a cell, the virus forces it to make thousands more viruses. It does this by making the cell copy the virus's DNA or RNA, making viral proteins, which all assemble to form new virus particles. [Shors pp. 11–12]

There are six basic, overlapping stages in the life cycle of viruses in living cells: [Shors pp. 47–67 ]

*Attachment is the binding of the virus to specific molecules on the surface of the cell. This specificity restricts the virus to a very limited type of cell. For example, the human immunodeficiency virus (HIV) infects only human T cells, because its surface protein, gp120, can only react with CD4 and other molecules on the T cell's surface. Plant viruses can only attach to plant cells and cannot infect animals. This mechanism has evolved to favour those viruses that only infect cells in which they are capable of reproducing.
*Penetration follows attachment; viruses penetrate the host cell by endocytosis or by fusion with the cell.

*Uncoating happens inside the cell when the viral capsid is removed and destroyed by viral enzymes or host enzymes, thereby exposing the viral nucleic acid.

*Replication of virus particles is the stage where a cell uses viral messenger RNA in its protein synthesis systems to produce viral proteins. The RNA or DNA synthesis abilities of the cell produce the virus's DNA or RNA.

*Assembly takes place in the cell when the newly created viral proteins and nucleic acid combine to form hundreds of new virus particles.

*Release occurs when the new viruses escape or are released from the cell. Most viruses achieve this by making the cells burst, a process called lysis. Other viruses such as HIV are released more gently by a process called budding.

Viruses and diseases

:"For more examples of diseases caused by viruses see List of infectious diseases"Human diseases caused by viruses include the common cold, the flu, chickenpox and cold sores. Serious diseases such as Ebola, AIDS and influenza are also caused by viruses. Many viruses cause little or no disease and are said to be "benign". The more harmful viruses are described as virulent.Viruses cause different diseases depending on the types of cell that they infect. Some viruses can cause life-long or chronic infections where the viruses continue to reproduce in the body despite the host's defence mechanisms. [Shors p. 483] This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected with a virus are known as carriers. They serve as important reservoirs of the virus. If there is a high proportion of carriers in a given population, a disease is said to be endemic. [Topley and Wilson p. 766 ]

There are many ways in which viruses spread from host to host but each species of virus uses only one or two. Many viruses that infect plants are carried by organisms; such organisms are called vectors. Some viruses that infect animals and humans are also spread by vectors, usually blood-sucking insects. However, direct animal-to-animal, person-to-person or animal-to-person transmission is more common. Some virus infections, (norovirus and rotavirus), are spread by contaminated food and water, hands and communal objects and by intimate contact with another infected person , [Shors p. 118] while others are airborne (influenza virus). [Shors p.117] Viruses such as HIV, hepatitis B and hepatitis C are often transmitted by unprotected sex [Shors p. 119] or contaminated hypodermic needles. [Shors p.123] It is important to know how each different kind of virus is spread to prevent infections and epidemics. [Shors pp. 16–19]

Diseases of plants

There are many types of plant virus, but often they only cause a loss of yield, and it is not economically viable to try to control them. Plant viruses are often spread from plant to plant by organisms, known as "vectors". These are normally insects, but some fungi, nematode worms and single-celled organisms have been shown to be vectors. When control of plant virus infections is considered economical, (for perennial fruits for example), efforts are concentrated on killing the vectors and removing alternate hosts such as weeds. [ Shors p. 584 ] Plant viruses are harmless to humans and other animals because they can only reproduce in living plant cells. [Shors pp. 562–587]

Bacteriophages

Bacteriophages are viruses that infect bacteria. There are over 5,100 types of bacteriophages. They are important in marine ecology: as the infected bacteria burst, carbon compounds are released back into the environment, which stimulates fresh organic growth. Bacteriophages are useful in scientific research because they are harmless to humans and can be studied easily. These viruses can be a problem in industries that produce food and drugs by fermentation and depend on healthy bacteria. Some bacterial infections are becoming difficult to control with antibiotics, so there is a growing interest in the use of bacteriophages to treat infections in humans. [Shors pp. 588–604]

Host resistance

Innate immunity of animals

Animals, including humans, have many natural defences against viruses. Some are non-specific and protect against many viruses regardless of the type. This innate immunity is not improved by repeated exposure to viruses and does not retain a "memory" of the infection. The skin of animals, particularly its surface, which is made from dead cells, prevents many types of viruses from infecting the host. The acidity of the contents of the stomach kills many viruses that have been swallowed. When a virus overcomes these barriers and enters the host, other innate defences prevent the spread of infection in the body. A special hormone called interferon is produced by the body when viruses are present, and this stops the viruses from reproducing by killing the infected cell and its close neighbours. Inside cells, there are enzymes that destroy the RNA of viruses. This is called RNA interference. Some blood cells engulf and destroy other virus infected cells. [Shors pp. 146–158]

Adaptive immunity of animals

Specific immunity to viruses develops over time and white blood cells called lymphocytes play a central role. These cells retain a "memory" of virus infections and produce many molecules called antibodies which attach to viruses and prevent their attachment to cells. These antibodies are highly selective and kill only one type of virus. The body makes many different antibodies and each kind is specific for different types of viruses. During the initial infection, the body makes these antibodies in abundance, but after the infection subsides, some antibodies remain and continue to be produced and protect the host. This protection is often life-long. [Shors pp.158–168]

Plant resistance

Plants have elaborate and effective defence mechanisms against viruses. One of the most effective is the presence of so-called resistance (R) genes. Each R gene confers resistance to a particular virus by triggering localised areas of cell death around the infected cell, which can often be seen with the unaided eye as large spots. This stops the infection from spreading. [Dinesh-Kumar, S.P., Wai-Hong Tham, Baker, B.J., (2000) "Structure—function analysis of the tobacco mosaic virus resistance gene N" "PNAS" 97, 14789-94 PMID 11121079 ] RNA interference is also an effective defence in plants. [Shors pp. 573–576] When they are infected, plants often produce natural disinfectants which kill viruses, such as salicylic acid, nitric oxide and reactive oxygen molecules. [Soosaar, J.L., Burch-Smith, T.M., Dinesh-Kumar, S.P. (2005) "Mechanisms of plant resistance to viruses" "Nat. Rev. Microbiol." 3, pp. 789–98 PMID 16132037 ]

Resistance to bacteriophages

The major way bacteria defend themselves from bacteriophages is by producing enzymes which destroy foreign DNA. These enzymes, called restriction endonucleases, cut up the viral DNA that bacteriophages inject into bacterial cells.

Prevention and treatment of viral disease in humans and other animals

Vaccines

Vaccination is a way of preventing diseases caused by viruses. Vaccines simulate a natural infection and its associated immune response, but do not cause the disease. Their use has resulted in a dramatic decline in illness and death caused by infections such as polio, measles, mumps and rubella. [Shors pp. 171–185] Vaccines are available to prevent over thirteen viral infections of humans [Shors p. 183] and more are used to prevent viral infections of animals. [Pastoret, P.P., Schudel, A.A., Lombard, M. (2007) "Conclusions—future trends in veterinary vaccinology". "Rev. Off. Int. Epizoot." 26, pp. 489–94, 495–501, 503–9. PMID 17892169] Vaccines may consist of either live or killed viruses. [Shors p. 172] Live vaccines contain weakened forms of the virus, but these vaccines can be dangerous when given to people with weak immunity. In these people, the weakened virus can cause the original disease. [Thomssen, R. (1975) "Live attenuated versus killed virus vaccines". "Monographs in allergy" 9, pp. 155–76. PMID 1090805 ] Biotechnology and genetic engineering techniques are used to produce "designer" vaccines that only have the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. [Shors p. 174] These vaccines are safer because they can never cause the disease. [Shors p. 180]

Antiviral drugs

Over the past 20 years, the development of antiviral drugs has increased rapidly, mainly driven by the AIDS epidemic. Antiviral drugs are often nucleoside analogues, which are molecules very similar, but not identical to DNA building blocks. When the replication of virus DNA begins, some of these fake building blocks are incorporated. As soon as that happens, replication stops prematurely— the fake building blocks lack the essential features that allow the addition of further building blocks. Thus, DNA production is halted, and the virus can no longer reproduce. [Shors p. 427] Examples of nucleoside analogues are aciclovir for herpes virus infections and lamivudine for HIV and hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. [Shors p. 426]

Other antiviral drugs target different stages of the viral life cycle. HIV is dependent on an enzyme called the HIV-1 protease for the virus to become infectious. There is a class of drugs called protease inhibitors, which bind to this enzyme and stop it from functioning. [Shors p. 463]

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease becomes chronic, and they remain infectious for the rest of their lives unless they are treated. There is an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. [Witthoft, T., Moller, B., Wiedmann, K.H., Mauss, S., Link, R., Lohmeyer, J., Lafrenz, M., Gelbmann, C.M., Huppe, D., Niederau, C., Alshuth, U. (2007) "Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial." "J Viral Hepat." 14, pp. 788–796. PMID 17927615] The treatment for chronic carriers of the hepatitis B virus by a similar strategy using lamivudine is being developed. [Rudin, D., Shah, S.M., Kiss, A., Wetz, R.V., Sottile, V.M. (2007) "Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials." "Liver Int." 9, pp. 1185–93. PMID 17919229] In both diseases, the ribavirin stops the virus from reproducing and the interferon kills any remaining infected cells.

HIV infections are usually treated with a combination of antiviral drugs, each targeting a different stage in the virus's life-cycle. There are drugs that prevent the virus from attaching to cells, others that are nucleoside analogues and some poison the virus's enzymes that it needs to reproduce. [Shors p. 463] The success of these drugs is proof of the importance of knowing how viruses reproduce.

ee also

*Hepatitis C
*Herpes simplex virus
*Herpes simplex
*Herpes zoster

Notes

References

*Collier, Leslie; Balows, Albert; Sussman Max (1998) "Topley and Wilson's Microbiology and Microbial Infections" ninth edition, Volume 1, "Virology", volume editors: Mahy, Brian and Collier, Leslie. Arnold. ISBN 0340663162
*Shors, Teri (2008). "Understanding Viruses". Jones and Bartlett Publishers. ISBN 0763729329

External links

* [http://www.hpa.org.uk UK Health Protection Agency]
* [http://www.cdc.gov US Centers for Disease Control and Prevention]