Virus
From Wikipedia, the free encyclopedia
This article is about the biological agent. For other uses, see
Virus (disambiguation).
For a generally accessible and less technical introduction to the topic, see
Introduction to viruses.
Viruses consist of two or three parts: all viruses have
genes made from either
DNA or
RNA, long
molecules that carry genetic information; all have a
protein coat that protects these genes; and some have an
envelope of fat that surrounds them when they are outside a cell. Viruses vary in shape from simple
helical and
icosahedral shapes, to more complex structures. They are about 1/100th the size of
bacteria.
[7] The origins of viruses are unclear: some may have
evolved from
plasmids—pieces of DNA that can move between cells—others may have evolved from bacteria. In evolution, viruses are an important means of
horizontal gene transfer.
[8] Viruses spread in many ways; plant viruses are often transmitted from plant to plant by insects that feed on
sap, such as
aphids, while animal viruses can be carried by
blood-sucking insects. These disease-bearing organisms are known as
vectors.
Influenza viruses are spread by coughing and sneezing, and others such as
norovirus, are transmitted by the
faecal-oral route, when they contaminate hands, food or water.
Rotaviruses are often spread by direct contact with infected children.
HIV is one of several viruses that are transmitted through
sexual contact.
Not all viruses cause disease, as many viruses reproduce without causing any obvious harm to the infected organism. Some viruses such as hepatitis B can cause life-long or
chronic infections, and the viruses continue to replicate in the body despite the hosts' defence mechanisms. However, viral infections in animals usually cause an
immune response, which can completely eliminate a virus. These immune responses can also be produced by
vaccines that give lifelong
immunity to a viral infection. Microorganisms such as bacteria also have defences against viral infection, such as
restriction modification systems.
Antibiotics have no effect on viruses, but
antiviral drugs have been developed to treat life-threatening and more minor infections.
Etymology
The word is from the
Latin virus referring to
poison and other noxious substances, first used in English in 1392.
[9] Virulent, from Latin virulentus (poisonous) dates to 1400.
[10] A meaning of "agent that causes infectious disease" is first recorded in 1728,
[9] before the discovery of viruses by
Dmitry Ivanovsky in 1892. The adjective viral dates to 1948.
[11] The term virion is also used to refer to a single infective viral particle. The
plural of virus is "viruses".
HistoryMartinus Beijerinck in his laboratory in 1921
In 1884, the French
microbiologist Charles Chamberland invented a filter (known today as the
Chamberland filter or Chamberland-Pasteur filter), with pores smaller than bacteria. Thus, he could pass a solution containing bacteria through the filter and completely remove them from the solution.
[12] In 1892 the Russian biologist
Dimitri Ivanovski used this filter to study what is now known to be
tobacco mosaic virus. His experiments showed that the crushed leaf extracts from infected tobacco plants are still infectious after filtration. Ivanovski suggested the infection might be caused by a toxin produced by bacteria, but did not pursue the idea.
[13] 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.
[2] In 1898 the Dutch microbiologist
Martinus Beijerinck repeated the experiments and became convinced that this was a new form of infectious agent.
[14] He went on to observe that the agent multiplied only in dividing cells, but as his experiments did not show that it was made of particles, he called it a contagium vivum fluidum (soluble living germ) and re-introduced the word virus.
[13] Beijerinck maintained that viruses were liquid in nature, a theory later discredited by
Wendell Stanley, who proved they were particulate.
[13] In the same year, 1899,
Friedrich Loeffler and Frosch passed the agent of
foot and mouth disease (
aphthovirus) through a similar filter and ruled out the possibility of a toxin because of the high dilution; they concluded that the agent could replicate.
[13]In the early 20th century, the English bacteriologist
Frederick Twort discovered the viruses that infect bacteria, which are now called
bacteriophages,
[15] and the French-Canadian microbiologist
Félix d'Herelle described viruses that, when added to bacteria on
agar, would produce areas of dead bacteria. He accurately diluted a suspension of these viruses and discovered that the highest dilutions, 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 suspension.
[16]By the end of the nineteenth century, viruses were defined in terms of their infectivity, filterability, and their requirement for living hosts. Viruses had only been grown in plants and animals. In 1906, Harrison invented a method for growing
tissue in
lymph, and, in 1913, E. Steinhardt, C. Israeli and R. A. Lambert used this method to grow
vaccinia virus in fragments of guinea pig corneal tissue.
[17] 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.
[18]Another breakthrough came in 1931, when the American pathologist
Ernest William Goodpasture grew influenza and several other viruses in fertilised chickens' eggs.
[19] In 1949
John F. Enders,
Thomas Weller and
Frederick Robbins grew polio virus in cultured human embryo cells, the first virus to be grown without using solid animal tissue or eggs. This work enabled
Jonas Salk to make an effective polio vaccine.
[20]Rosalind Franklin 
With the invention of
electron microscopy in 1931 by the German engineers
Ernst Ruska and
Max Knoll came the first images of viruses.
[21] In 1935 American biochemist and virologist Wendell Stanley examined the Tobacco mosaic virus and found it to be mostly made from protein.
[22] A short time later, this virus was separated into protein and RNA parts.
[23] Tobacco mosaic virus was the first one to be
crystallised and whose 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 pictures,
Rosalind Franklin discovered the full structure of the virus in 1955.
[24] In the same year,
Heinz Fraenkel-Conrat and
Robley Williams showed that purified Tobacco mosaic virus RNA and its coat protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism was probably how viruses assembled within their host cells.
[25]The second half of the twentieth century was the golden age of virus discovery and most of the 2,000 recognised species of animal, plant and bacterial viruses were discovered during these years.
[26][27] In 1957,
equine arterivirus and the cause of
Bovine virus diarrhea (a
pestivirus) were discovered. In 1963, the
hepatitis B virus was discovered by
Baruch Blumberg,
[28] and in 1965,
Howard Temin described the first
retrovirus.
Reverse transcriptase, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and
David Baltimore.
[29] In 1983
Luc Montagnier's team at the
Pasteur Institute in
France, first isolated the retrovirus now called HIV.
[30]Origins
Viruses are found wherever there is life and have probably existed since living cells first evolved.
[31] The origin of viruses is unclear because they do not form fossils, so
molecular techniques have been the most useful means of investigating how they arose.
[32] 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.
[33][34] There are three main hypotheses that try to explain the origins of viruses:
[35][36] Regressive hypothesisViruses 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 support to this hypothesis, as their dependence on parasitism is likely to have caused the loss of genes that enabled them to survive outside a cell. This is also called the degeneracy hypothesis.
[37][38] Cellular origin hypothesis (sometimes called the vagrancy hypothesis)[37][39]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 naked DNA that can move between cells) or
transposons (molecules of DNA that replicate and move around to different positions within the genes of the cell).
[40] Once called "jumping genes", transposons are examples of
mobile genetic elements and could be the origin of some viruses. They were discovered in maize by
Barbara McClintock in 1950.
[41] Coevolution hypothesisViruses may have evolved from complex molecules of protein and nucleic acid at the same time as cells first appeared on earth and would have been dependent on cellular life for many millions of years.
Viroids are molecules of RNA that are not classified as viruses because they lack a protein coat. However, they have characteristics that are common to several viruses and are often called subviral agents.
[42] Viroids are important pathogens of plants.
[43] They do not code for proteins but interact with the host cell and use the host machinery for their replication.
[44] The
hepatitis delta virus of humans has an RNA genome similar to viroids but has protein coat derived from hepatitis B virus and cannot produce one of its own. It is therefore a defective virus and cannot replicate without the help of hepatitis B virus.
[45]The
Virophage 'sputnik' infects the
Mimivirus and the related Mamavirus, which in turn infect the protozooan Acanthamoeba castellanii.
[46] These viruses that are dependent on other virus species are called
satellites and may represent evolutionary intermediates of viroids and viruses.
[47][48] Prions are infectious protein molecules that do not contain DNA or RNA.
[49] They cause an infection in sheep called
scrapie and cattle
bovine spongiform encephalopathy ("mad cow" disease). In humans they cause
kuru and
Creutzfeld-Jacob disease.
[50] They are able to replicate because some proteins can exist in two different shapes and the prion changes the normal shape of a host protein into the prion shape. This starts a chain reaction where each prion protein converts many host proteins into more prions, and these new prions then go on to convert even more protein into prions. Although they are fundamentally different from viruses and viroids, their discovery gives credence to the idea that viruses could have evolved from self-replicating molecules.
[51]Computer analysis of viral and host DNA sequences is giving a better understanding of the evolutionary relationships between different viruses and may help identify the ancestors of modern viruses. To date, such analyses have not helped to decide on which of these hypotheses are correct. However, it seems unlikely that all currently known viruses have a common ancestor and viruses have probably arisen numerous times in the past by one or more mechanisms.
[52]Opinions differ on whether viruses are a form of life, or organic structures that interact with living organisms. They have been described as "organisms at the edge of life",
[53] since they resemble organisms in that they possess genes and evolve by natural selection,
[54] and reproduce by creating multiple copies of themselves through self-assembly. However, although they have genes, they do not have a cellular structure, which is often seen as the basic unit of life. Additionally, viruses do not have their own
metabolism, and require a host cell to make new products. They therefore cannot reproduce outside a host cell (although bacterial species such as rickettsia and chlamydia are considered living organisms despite the same limitation). Accepted forms of life use
cell division to reproduce, whereas viruses spontaneously assemble within cells, which is analogous to the autonomous growth of
crystals. Virus self-assembly within host cells has implications for the study of the
origin of life, as it lends further credence to the hypothesis that life could have started as self-assembling organic molecules.
[1]StructureDiagram of how a virus capsid can be constructed using multiple copies of just two protein molecules
Viruses display a wide diversity of shapes and sizes, called
morphologies. Viruses are about 1/100th the size of bacteria. Most viruses that have been studied have a diameter between 10 and 300
nanometres. Some
filoviruses have a total length of up to 1400 nm, however their diameters are only about 80 nm.
[7] Most viruses are unable to be seen with a
light microscope so scanning and transmission
electron microscopes are used to visualise virus particles.
[55] To increase the contrast between viruses and the background, electron-dense "stains" are used.
These are solutions of salts of heavy metals such as
tungsten, that scatter the electrons from regions covered with the stain. When virus particles are coated with stain (positive staining), fine detail is obscured.
Negative staining overcomes this problem by staining the background only.
[56]A complete virus particle, known as a virion, consists of
nucleic acid surrounded by a protective coat of protein called a capsid. These are formed from identical protein subunits called capsomers.
[57] Viruses can have a
lipid "envelope" derived from the host
cell membrane. The
capsid is made from proteins encoded by the viral
genome and its shape serves as the basis for morphological distinction.
[58][59] Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins that assist in the construction of their capsid. Proteins associated with nucleic acid are known as
nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. The capsid and entire virus structure can be mechanically (physically) probed through
atomic force microscopy.
[60][61] In general, there are four main morphological
HelicalThese viruses are composed of a single type of capsomer stacked around a central axis to form a helical structure, which may have a central cavity, or hollow tube. This arrangement results in rod-shaped or filamentous virions: these can be short and highly rigid, or long and very flexible. The genetic material, generally single-stranded RNA, but ssDNA in some cases, is bound into the protein helix, by interactions between the negatively charged nucleic acid and positive charges on the protein. Overall, the length of a helical capsid is related to the length of the nucleic acid contained within it and the diameter is dependent on the size and arrangement of capsomers. The well-studied Tobacco mosaic virus is an example of a helical virus.
[62] Icosahedral
Most animal viruses are icosahedral or near-spherical with icosahedral symmetry. A regular icosahedron is the optimum way of forming a closed shell from identical sub-units. The minimum number of identical capsomers required is twelve, each composed of five identical sub-units. Many viruses, such as rotavirus, have more than twelve capsomers and appear spherical but they retain this symmetry. Capsomers at the apices are surrounded by five other capsomers and are called pentons. Capsomers on the triangular faces are surround by six others and are call hexons.
[63] Envelope
Some species of virus envelope themselves in a modified form of one of the
cell membranes, either the outer membrane surrounding an infected host cell,
or internal membranes such as nuclear membrane or
endoplasmic reticulum, thus gaining an outer lipid bilayer known as a viral envelope. This membrane is studded with proteins coded for by the viral genome and host genome; the lipid membrane itself and any carbohydrates present originate entirely from the host. The influenza virus and HIV use this strategy. Most enveloped viruses are dependent on the envelope for their infectivity.
[64] ComplexThese viruses possess a capsid that is neither purely helical, nor purely icosahedral, and that may possess extra structures such as protein tails or a complex outer wall. Some bacteriophages have a complex structure consisting of an icosahedral head boun
d to a helical tail, which may have a hexagonal base plate with protruding protein tail fibres.
The poxviruses are large, complex viruses that have an unusual
morphology. The viral genome is associated with proteins within a central disk structure known as a
nucleoid. The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole particle is slightly
pleiomorphic, ranging from ovoid to brick shape.
[65] Mimivirus is the largest known virus, with a capsid diameter of 400 nm. Protein filaments measuring 100 nm project from the surface. The capsid appears hexagonal under an electron microscope, therefore the capsid is probably icosahedral.
[66]Genomes
Genomic diversity among viruses
Property
Parameters
Nucleic acid
DNA
RNA
Both DNA and RNA (at different stages in the life cycle)
Shape
Linear
Circular
Segmented
Strandedness
Single-stranded
Double-stranded
Double-stranded with regions of single-strandedness
SensePositive sense (+)
Negative sense (−)
Ambisense (+/−)
An enormous variety of genomic structures can be seen among viral species; as a group they contain more structural genomic diversity than the entire kingdoms of either plants, animals, or bacteria. A virus has either DNA or RNA genes and are called DNA viruses and RNA viruses respectively. By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA.
[67]Viral genomes are circular, such as
polyomaviruses, or linear, such as
adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses, the genome is often divided up into separate parts within the virion and is called segmented. Each segment often codes for one protein and they are usually found together in one capsid. Every segment is not required to be in the same virion for the overall virus to be infectious, as demonstrated by the
brome mosaic virus.
[7]A viral genome, irrespective of nucleic acid type, is either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to a ladder. Some viruses, such as those belonging to the
Hepadnaviridae, contain a genome that is partially double-stranded and partially single-stranded.
[67]For viruses with RNA or single-stranded DNA, the strands are said to be either
positive-sense (called the plus-strand) or
negative-sense (called the minus-strand), depending on whether it is complementary to the viral
messenger RNA (mRNA). Positive-sense viral RNA is identical to viral mRNA and thus can be immediately
translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an
RNA polymerase before translation. DNA nomenclature is similar to RNA nomenclature, in that the coding strand for the viral mRNA is complementary to it (−), and the non-coding strand is a copy of it (+).
[67]Genome size varies greatly between species. The smallest viral genomes code for only four proteins and weigh about 106
Daltons; the largest weigh about 108 Daltons and code for over one hundred proteins.
[67] RNA viruses generally have smaller genome sizes than DNA viruses due to a higher error-rate when replicating, and have a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes where the genome is split into smaller molecules, thus reducing the chance of error. In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes.
[68]Genetic change 
How antigenic shift, or reassortment, can result in novel and highly pathogenic strains of human influenza
Viruses undergo genetic change by several mechanisms. These include a process called
genetic drift where individual bases in the DNA or RNA
mutate to other bases. Most of these
point mutations are silent in that they do not change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to
antiviral drugs.
[69] Antigenic shift is where there is a major change in the
genome of the virus. This occurs as a result of
recombination or
reassortment. When this happens with influenza viruses,
pandemics may result.
[70] RNA viruses often exist as
quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection.
[71]Segmented genomes confer evolutionary advantages; different strains of a virus with a segmented genome can shuffle and combine genes and produce progeny viruses or (offspring) that have unique characteristics. This is called reassortment or viral sex.
[72]Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of
viral evolution have shown that recombination has been rampant in the species studied.
[73] Recombination is common to both RNA and DNA viruses.
[74][75]Replication
Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.
Cycle
A typical virus replication cycle
Some bacteriophages inject their genomes into bacterial cells
The
life cycle of viruses differs greatly between species but there are six basic stages in the life cycle of viruses:
[76]Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, HIV infects only human
T cells, because its surface protein,
gp120, can interact with
CD4 and receptors on the T cell's surface. This mechanism has evolved to favour those viruses that only infect cells in which they are capable of replication. Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the
fusion of viral and cellular membranes.
Penetration follows attachment; viruses enter the host cell through receptor mediated
endocytosis or
membrane fusion. This is often called
viral entry. The infection of plant cells is different to that of animal cells. Plants have a rigid cell wall made of
cellulose and viruses can only get inside the cells following trauma to the cell wall.
[77] Viruses such as tobacco mosaic virus can also move directly in plants, from cell-to-cell, through pores called
plasmodesmata.
[78] Bacteria, like plants, have strong cell walls that a virus must breach to infect the cell. Some viruses have evolved mechanisms that inject their genome into the bacterial cell while the viral capsid remains outside.
[79]Uncoating is a process in which the viral capsid is degraded by viral
enzymes or host enzymes thus releasing the viral genomic nucleic acid.
Replication involves synthesis of viral messenger RNA (mRNA) for viruses except positive sense RNA viruses (see above), viral
protein synthesis and assembly of viral proteins and viral genome replication.
Following the assembly of the virus particles, post-translational modification of the viral proteins often occurs. In viruses such as HIV, this modification, (sometimes called maturation), occurs after the virus has been released from the host cell.
[80]Viruses are released from the host cell by
lysis—a process that kills the cell by bursting its membrane. Enveloped viruses (e.g., HIV) typically are released from the host cell by
budding. During this process the virus acquires its envelope, which is a modified piece of the host's plasma membrane.
TypeGenetic material within viruses, and the method by which the material is replicated, vary between different types of viruses.
DNA virusesThe genome replication of most DNA viruses takes place in the cell's
nucleus. If the cell has the appropriate receptor on its surface, these viruses enter the cell by fusion with the cell membrane or by endocytosis. Most DNA viruses are entirely dependent on the host cell's DNA and RNA synthesising machinery, and RNA processing machinery. The viral genome must cross the cell's nuclear membrane to access this machinery.
[81] RNA viruses
These viruses are unique because their genetic information is encoded in RNA. Replication usually takes place in the
cytoplasm. RNA viruses can be placed into about four different groups depending on their modes of replication. The
polarity (whether or not it can be used directly to make proteins) of the RNA largely determines the replicative mechanism, and whether the genetic material is single-stranded or double-stranded. RNA viruses use their own
RNA replicase enzymes to create copies of their genomes.
[82] Reverse transcribing virusesThese replicate using reverse transcription, which is the formation of DNA from an RNA template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types use the
reverse transcriptase enzyme to carry out the nucleic acid conversion.
Retroviruses often integrate the DNA produced by
reverse transcription into the host genome. They are susceptible to
antiviral drugs that inhibit the reverse transcriptase enzyme, e.g.
zidovudine and
lamivudine. An example of the first type is HIV, which is a retrovirus. Examples of the second type are the
Hepadnaviridae, which includes Hepatitis B virus.
[83]Effects on the host cellThe range of structural and biochemical effects that viruses have on the hosts cell is extensive.
[84] These are called cytopathic effects.
[85] Most virus infections eventually result in the death of the host cell. The causes of death include cell lysis, alterations to the cell's surface membrane and
apoptosis.
[86] Often cell death is caused by cessation of its normal activities due to suppression by virus-specific proteins, not all of which are components of the virus particle.
[87]Some viruses cause no apparent changes to the infected cell. Cells in which the virus is
latent and inactive show few signs of infection and often function normally.
[88] This causes persistent infections and the virus is often dormant for many months or years. This is often the case with
herpes viruses.
[89][90] Viruses, such as
Epstein-Barr virus often cause cells to proliferate without causing malignancy,
[91] but viruses, such as
papillomaviruses are an established cause of cancer.
[92]Classification
Main article:
Virus classificationClassification seeks to describe the diversity of viruses by naming and grouping them based on similarities. In 1962,
André Lwoff, Robert Horne, and
Paul Tournier were the first to develop a means of virus classification, based on the
Linnaean hierarchical system.
[93] This system bases classification on
phylum,
class,
order,
family,
genus, and
species. Viruses were grouped according to their shared properties (not of their hosts) and the type of nucleic acid forming their genomes.
[94] later the
International Committee on Taxonomy of Viruses was formed.
ICTV classification
The
International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and wrote guidelines that put a greater weight on certain virus properties to maintain family uniformity. A universal system for classifying viruses, and a unified taxonomy, has been established since 1966. The 7th lCTV Report formalised for the first time the concept of the virus species as the lowest taxon (group) in a branching hierarchy of viral taxa.
[95] However, at present only a small part of the total diversity of viruses has been studied, with analyses of samples from humans finding that about 20% of the virus sequences recovered have not been seen before, and samples from the environment, such as from seawater and ocean sediments, finding that the large majority of sequences are completely novel.
[96]The general taxonomic structure is as follows:
Order (-virales)
Family (-viridae)
Subfamily (-virinae)
Genus (-virus)
Species (-virus)
In the current (2008) ICTV taxonomy, five orders have been established, the Caudovirales, Herpesvirales, Mononegavirales, Nidovirales, and Picornavirales. The committee does not formally distinguish between
subspecies,
strains, and
isolates. In total there are 5 orders, 82 families, 11 subfamilies, 307 genera, 2,083 species and about 3,000 types yet unclassified.
[97][98]Baltimore classificationMain article:
Baltimore classification 
The Baltimore Classification of viruses is based on the method of viral
mRNA synthesis.
The
Nobel Prize-winning biologist
David Baltimore devised the
Baltimore classification system.
[29][99] The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.
[100][101][102]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). Additionally, ssRNA viruses may be either
sense (+) or antisense (-). This classification places viruses into seven groups:
I:
dsDNA viruses (e.g.
Adenoviruses,
Herpesviruses,
Poxviruses)
II:
ssDNA viruses (+)sense DNA (e.g.
Parvoviruses)
III:
dsRNA viruses (e.g.
Reoviruses)
IV:
(+)ssRNA viruses (+)sense RNA (e.g.
Picornaviruses,
Togaviruses)
V:
(-)ssRNA viruses (-)sense RNA (e.g.
Orthomyxoviruses,
Rhabdoviruses)
VI:
ssRNA-RT viruses (+)sense RNA with DNA intermediate in life-cycle (e.g.
Retroviruses)
VII:
dsDNA-RT viruses (e.g.
Hepadnaviruses)
As an example of viral classification, the
chicken pox virus,
varicella zoster (VZV), belongs to the order Herpesvirales, family
Herpesviridae, subfamily
Alphaherpesvirinae, and genus
Varicellovirus. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase.
Viruses and human diseaseSee also:
Table of clinically important viruses 
Overview of the main types of viral infection and the most notable species involved.
[103] [104]Examples of common human diseases caused by viruses include the
common cold, influenza,
chickenpox and
cold sores. Many serious diseases such as
ebola,
AIDS,
avian influenza and
SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of
virulence. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between
human herpes virus six (HHV6) and neurological diseases such as
multiple sclerosis and
chronic fatigue syndrome. There is current controversy over whether the
borna virus, previously thought to cause
neurological diseases in horses, could be responsible for
psychiatric illnesses in humans.
[105]Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In
multicellular organisms, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy
homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the
herpes simplex virus, which cause cold sores, to remain in a dormant state within the human body. This is called latency
[106] and is a characteristic of the all herpes viruses including the Epstein-Barr virus, which causes glandular fever, and the varicella zoster virus, which causes chicken pox. Latent chickenpox infections return in later life as the disease called
shingles.
Some viruses can cause life-long or
chronic infections, where the viruses continue to replicate in the body despite the hosts' defence mechanisms.
[107] This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus.
[108] In populations with a high proportion of carriers, the disease is said to be
endemic.
[109] In contrast to acute lytic viral infections this persistence implies compatible interactions with the host organism. Persistent viruses may even broaden the evolutionary potential of host species.
[110]EpidemiologyViral
epidemiology is the branch of medical science that deals with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of
vertical transmission include hepatitis B virus and HIV where the baby is born already infected with the virus.
[111] Another, more rare, example is the varicella zoster virus, which although causing relatively mild infections in humans, can be fatal to the foetus and newly born baby.
[112] Horizontal transmission is the most common mechanism of spread of viruses in populations. Transmission can be exchange of blood by sexual activity, e.g. HIV, hepatitis B and hepatitis C; by mouth by exchange of saliva, e.g. Epstein-Barr virus, or from contaminated food or water, e.g. norovirus; by breathing in viruses in the form of
aerosols, e.g. influenza virus; and by insect vectors such as mosquitoes, e.g.
dengue. The rate or speed of transmission of viral infections depends on factors that include
population density, the number of susceptible individuals, (i.e. those who are not immune),
[113] the quality of health care and the weather.
[114]Epidemiology is used to break the chain of infection in populations during outbreaks of viral diseases.
[115] Control measures are used that are based on knowledge of how the virus is transmitted. It is important to find the source, or sources, of the outbreak and to identify the virus. Once the virus has been identified, the chain of transmission can sometimes be broken by vaccines. When vaccines are not available sanitation and disinfection can be effective. Often infected people are isolated from the rest of the community and those that have been exposed to the virus placed in
quarantine.
[116] To control the outbreak of
foot and mouth disease in cattle in Britain in 2001, thousands of cattle were slaughtered.
[117] Most viral infections of humans and other animals have
incubation periods during which the infection causes no signs or symptoms.
[118] Incubation periods for viral diseases range from a few days to weeks but are known for most infections.
[119] Following the incubation period there is a period of communicability; a time when an infected individual or animal is contagious and can infect another person or animal.
[120] This too is known for many viral infections and knowledge the length of both periods is important in the control of outbreaks.
[121] When outbreaks cause an unusually high proportion of cases in a population, community or region they are called
epidemics. If outbreaks spread worldwide they are called
pandemics.
[122]Epidemics and pandemics
See also:
Spanish flu,
AIDS, and
Ebola 
For more details on this topic, see
List of epidemics.
The reconstructed
1918 influenza virus
Native American populations were devastated by contagious diseases, particularly
smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population.
[123]A
pandemic is a worldwide epidemic. The 1918 flu pandemic, commonly referred to as the Spanish flu, was a
category 5 influenza pandemic caused by an unusually severe and deadly influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or otherwise weakened patients.
[124]The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people,
[125] while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918.
[126] Most researchers believe that HIV originated in
sub-Saharan Africa during the twentieth century;
[127] it is now a
pandemic, with an estimated 38.6 million people now living with the disease worldwide.
[128] The
Joint United Nations Programme on HIV/AIDS (UNAIDS) and the
World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognised on June 5, 1981, making it one of the most destructive
epidemics in recorded history.
[129] In 2007 there were 2.7 million new HIV infections and 2 million HIV-related deaths.
[130]Marburg virusSeveral highly lethal viral pathogens are members of the
Filoviridae. Filoviruses are filament-like viruses that cause
viral hemorrhagic fever, and include the ebola and
marburg viruses. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in
Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever.
[131]Cancer
For more details on this topic, see
Oncovirus.
Viruses are an established cause of
cancer in humans and other species. However, cancer is not an infectious disease. Instead, the presence of the virus increases the risk that cells in the body will become cancerous. The main viruses associated with human cancers are
human papillomavirus, hepatitis B virus, Epstein-Barr virus, and
human T-lymphotropic virus. Hepatitis viruses can induce a chronic viral infection that leads to
liver cancer.
[132][133] Infection by human T-lymphotropic virus can lead to
tropical spastic paraparesis and
adult T-cell leukemia.
[134] Human papillomaviruses are an established cause of cancers of
cervix, skin,
anus, and
penis.
[135] Within the
Herpesviridae,
Kaposi's sarcoma-associated herpesvirus causes
Kaposi's sarcoma and body cavity lymphoma, and Epstein–Barr virus causes
Burkitt's lymphoma,
Hodgkin’s lymphoma,
B lymphoproliferative disorder and
nasopharyngeal carcinoma.
[136]Host defence mechanisms
See also:
Immune systemThe body's first line of defence against viruses is the
innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognise, and respond to, pathogens in a generic way, but unlike the
adaptive immune system, it does not confer long-lasting or protective immunity to the host.
[137]RNA interference is an important innate defence against viruses.
[138] Many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called
dicer that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated, which degrades the viral mRNA and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic dsRNA remains protected inside the core of the virion.
[139][140]When the
adaptive immune system of a
vertebrate encounters a virus, it produces specific
antibodies that bind to the virus and render it non-infectious. This is called
humoral immunity. Two types of antibodies are important. The first called IgM is highly effective at neutralizing viruses but is only produced by the cells of the immune system for a few weeks. The second, called, IgG is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past.
[141] IgG antibody is measured when tests for
immunity are carried out.
[142]Two rotaviruses: the one on the right is coated with antibodies that stop its attaching to cells and infecting them
A second defence of vertebrates against viruses is called
cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognises a suspicious viral fragment there, the host cell is destroyed by T killer cells and the virus-specific T-cells proliferate. Cells such as the
macrophage are specialists at this
antigen presentation.
[143] The production of
interferon is an important host defence mechanism. This is a hormone produced by the body when viruses are present. Its role in immunity is complex, but it eventually stops the viruses from reproducing by killing the infected cell and its close neighbours
[144]Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of
antigen presentation,
cytokine resistance, evasion of
natural killer cell activities, escape from
apoptosis, and antigenic shift.
[145] Other viruses, called
neurotropic viruses, are disseminated by neural spread where the immune system may be unable to reach them.
Prevention and treatment
Because viruses use the machinery of a host cell to reproduce and reside within them, they are difficult to eliminate without killing the host cell. The most effective medical approaches to viral diseases so far are
vaccinations to provide resistance to infection, and
antiviral drugs.
VaccinesFor more details on this topic, see
Vaccination.
Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as
polio,
measles,
mumps and
rubella.
[146] Smallpox infections have been eradicated.
[147] Currently vaccines are available to prevent over thirteen viral infections of humans,
[148] and more are used to prevent viral infections of animals.
[149] Vaccines can consist of live-attenuated or killed viruses, or viral proteins (
antigens).
[150] Live vaccines contain weakened forms of the virus that causes the disease. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as
immunocompromised), because in these people, the weakened virus can cause the original disease.
[151] Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine.
[152] Subunit vaccines are safe for
immunocompromised patients because they cannot cause the disease.
[153] However, the yellow fever virus vaccine, a live-attenuated strain called 17D, is probably the safest and most effective vaccine ever generated.
[154]Antiviral drugs
For more details on this topic, see
Antiviral drug.
GuanosineThe guanosine analogue
AciclovirOver the past twenty years, the development of
antiviral drugs has increased rapidly. This has been driven by the AIDS epidemic. Antiviral drugs are often
nucleoside analogues, (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesised DNA is inactive. This is because these analogues lack the
hydroxyl groups, which, along with
phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA
chain termination.
[155] Examples of nucleoside analogues are
aciclovir for Herpes simplex virus infections and
lamivudine for HIV and Hepatitis B virus infections.
Aciclovir is one of the oldest and most frequently prescribed antiviral drugs.
[156] Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the
HIV-1 protease for it to become fully infectious. There is a large class of drugs called
protease inhibitors that inactivate this enzyme.
Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is
chronic, and without treatment, they are
infected for the remainder of their lives. However, there is now an effective treatment that uses the nucleoside analogue drug
ribavirin combined with
interferon.
[157] The treatment of chronic
carriers of the hepatitis B virus by using a similar strategy using lamivudine has been developed.
[158]Infection in other speciesMain article:
Animal virologyViruses infect all cellular life and, although viruses occur universally, each cellular species has its own specific range that often only infect that species.
[159] Viruses are important pathogens of livestock. Diseases such as Foot and Mouth Disease and
bluetongue, are caused by viruses.
[160] Companion animals such as cats, dogs and horses, if not vaccinated, are susceptible to serious viral infections.
Canine parvovirus is caused by a small DNA virus and infections are often fatal in pups.
[161] Like all
invertebrates, the honey bee is susceptible to many viral infections.
[162] Fortunately, most viruses co-exist harmlessly in their host and cause no signs or symptoms of disease.
[2]Plants 
Main article:
Plant pathologyPeppers infected by mild mottle virus
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.
[163] Plant viruses are harmless to humans and other animals because they can only reproduce in living plant cells.
[164]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.
[165] RNA interference is also an effective defence in plants.
[166] When they are infected, plants often produce natural disinfectants that kill viruses, such as
salicylic acid,
nitric oxide and
reactive oxygen molecules.
[167]Bacteria
Main article:
Bacteriophage 
Transmission electron micrograph of multiple
bacteriophages attached to a bacterial cell wall
Bacteriophages are an extremely common and diverse group of viruses. For example, bacteriophages are the most common form of biological entity in aquatic environments, with up to ten times more of these viruses in the oceans than bacteria,
[168] reaching levels of 250,000,000 bacteriophages per
millilitre of seawater.
[169] These viruses infect specific bacteria by binding to
surface receptor molecules and then entering the cell. Within a short amount of time, in some cases just minutes, bacterial
polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins, which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and, in the case of the
T4 phage, in just over twenty minutes after injection over three hundred phages could be released.
[170]The major way bacteria defend themselves from bacteriophages is by producing enzymes that destroy foreign DNA. These enzymes, called
restriction endonucleases, cut up the viral DNA that bacteriophages inject into bacterial cells.
[171] Bacteria also contain a system that uses
CRISPR sequences to retain fragments of the genomes of viruses that the bacteria have come into contact with in the past, which allows them to block the virus's replication through a form of
RNA interference.
[172][173] This genetic system provides bacteria with
acquired immunity to infection.
Archaea
Some viruses replicate within
archaea: these are double-stranded DNA viruses that appear to be unrelated to any other form of virus and have a variety of unusual shapes, with some resembling bottles, hooked rods, or teardrops.
[5][174] These viruses have been studied in most detail in the thermophilic archaea, particularly the orders
Sulfolobales and
Thermoproteales.
[175] Defences against these viruses may involve
RNA interference from
repetitive DNA sequences within archaean genomes that are related to the genes of the viruses.
[176][177]ApplicationsLife sciences and medicineViruses are important to the study of
molecular and
cellular biology as they provide simple systems that can be used to manipulate and investigate the functions of cells.
[178] The study and use of viruses have provided valuable information about aspects of cell biology.
[179] For example, viruses have been useful in the study of
genetics and helped our understanding of the basic mechanisms of
molecular genetics, such as
DNA replication,
transcription,
RNA processing,
translation,
protein transport, and
immunology.
Geneticists often use viruses as
vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion,
virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in
gene therapy. Eastern European scientists have used
phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, due to the high level of
antibiotic resistance now found in some pathogenic bacteria.
[180]Materials science and nanotechnology
Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine.
[181]Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the
Naval Research Laboratory in
Washington, DC, using Cowpea Mosaic Virus (
CPMV) particles to amplify signals in
DNA microarray based sensors. In this application, the virus particles separate the
fluorescent dyes used for signaling in order to prevent the formation of non-fluorescent
dimers that act as
quenchers.
[182] Another example is the use of CPMV as a nanoscale breadboard for molecular electronics.
[183]WeaponsFor more details on this topic, see
Biological warfare.
Aztecs dying of smallpox, (“
The Florentine Codex” 1540-1585)
The ability of viruses to cause devastating
epidemics in human societies has led to the concern that viruses could be weaponised for
biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory.
[184] The
smallpox virus devastated numerous societies throughout history before its eradication. It currently exists only in several secure laboratories around the world, but fears that it may be used as a weapon are not totally unfounded; the vaccine for smallpox is not safe — during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox
[185] — and smallpox vaccination is no longer universally practiced.
[186] Thus, much of the modern human population has almost no established resistance to smallpox. If it were to be released, a massive loss of life could be sustained before the virus is brought under control.
is this nucleus that gives the eukaryote its name, which means "true nucleus." Other differences include: 
In addition to being filamentous, fungal cells often have multiple nuclei. In the chytrids and zygomycetes, the cells are coenocytic, with no distinction between individual cells. Rather, the filaments are long and tubular, with a cytoplasm lining and large vacuole in the center. By contrast, the ascomycetes and basidiomycetes are septate; their filaments are partitioned by cellular cross-walls called septa. The structure of these septa varies, and is taxonomically useful. 
_Virus_PHIL_1878_lores[1].jpg)
