Virus
This article is about a biological infectious particle; for the computer term, see computer virus. For other uses, see virus (disambiguation).In
taxonomy, the classification of viruses has proved to be rather difficult due to the lack of fossil record and dispute over whether they are living or non-living. They do not fit easily into any of the
domains of
biological classification and therefore classification begins at the
family rank. However, the domain name of
Acytota has been suggested. This would place viruses on a par with the other domains of
Eubacteria,
Archaea, and
Eukarya. Not all families are currently classified into orders, nor all genera classified into families.
As an example of viral classification, the
chicken pox virus belongs to family
Herpesviridae, subfamily
Alphaherpesvirinae and genus
Varicellovirus. It remains unranked in terms of order. The general structure is as follows.
Order (
-virales)::
Family (
-viridae):::Subfamily (
-virinae)::::
Genus (
-virus):::::
Species (
-virus)
The
International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and put in place guidelines that put a greater weighting on certain virus properties in order to maintain family uniformity. In determining order, taxonomists should consider the type of nucleic acid present, whether the nucleic acid is single- or double-stranded, and the presence or absence of an envelope. After these three main properties, other characteristics can be considered: the type of host, the capsid shape, immunological properties and the type of disease it causes.
In addition to this classification system, the
Nobel Prize-winning biologist
David Baltimore devised the
Baltimore classification system. This places a virus into one of seven
Groups, which separate viruses based on their mode of replication and genome type. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.
A complete virus particle, known as a
virion, is little more than a
gene transporter, consisting at the most basic level of
nucleic acid surrounded by a protective coat of
protein called a
capsid. A capsid is composed of proteins encoded by the viral
genome and its shape serves as the basis for
morphological distinction. Virally coded protein units called
protomers will self-assemble to form the capsid, requiring no input from the virus genome - however, a few viruses code for proteins which assist the construction of their capsid. Proteins associated with nucleic acid are more technically known as
nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a
nucleocapsid.
In general, four main morphological virus types can be identified:
| | Helical viruses | | Diagram of a helical capsid |
| Helical capsids are composed of a single type of protomer stacked around a central circumference to form an enclosed tube resembling a spiral staircase. This arrangement results in rod-shaped virions which can be short and rigid, or long and flexible. Long helical particles must be flexible in order to prevent forces snapping the structure. The genetic material is housed on the inside of the tube, protected from the outside. Overall, the length of a helical capsid is related to the length of the nucleic acid contained within it, while the diameter is dependent on the overall length and arrangement of protomers. The well-studied tobacco mosaic virus is a helical virus. |
| | Icosahedral viruses |
| Electron micrograph of icosahedral virions |
| Icosahedral capsid symmetry results in a spherical appearance of viruses at low magnification but actually consists of capsomers arranged in a regular geometrical pattern, similar to a soccer ball, hence they are not truly "spherical". Capsomers are ring shaped structures constructed from five to six copies of protomers. These associate via non-covalent bonding to enclose the viral nucleic acid, though generally less intimately than helical capsids, and may involve one type of protomer or more.
Icosahedral architecture was employed by R. Buckminster-Fuller in his geodesic dome, and is the most efficient way of creating an enclosed robust structure from multiple copies of a single protein. The number of proteins required to form a spherical virus capsid is denoted by the T-number[http://rhino.bocklabs.wisc.edu/cgi-bin/virusworld/htdocs.pl?docname=triangulation.html], where 60×t proteins are necessary. In the case of the hepatitis B virus the T-number is 4, therefore 240 proteins assemble to form the capsid. |
| | Enveloped viruses |
 | Diagram of enveloped HIV |
| In addition to a capsid some viruses are able to hijack a modified form of the cell membrane surrounding an infected host cell, thus gaining an outer lipid layer known as a viral envelope. This extra membrane is studded with proteins coded for by the viral genome and host genome, however the lipid membrane itself and any carbohydrates present are entirely host-coded.
The viral envelope can give a virion a few distinct advantages over other "naked" virions, such as protection from enzymes and chemicals. The proteins studded upon it can include glycoproteins functioning as receptor molecules, allowing healthy cells to recognise virions as "friendly" and resulting in the possible uptake of the virion into the cell. Some viruses, however, are so dependent upon their viral envelope that they fail to function if it is removed. |
| | Complex viruses |
| Diagram of a bacteriophage |
| These viruses possess a capsid which is neither purely helical, nor purely icosahedral, and which may possess extra structures such as protein tails or a complex outer wall. Some bacteriophages have a complex structure consisting of an icosahedral head bound to a helical tail, the latter of which may have a hexagonal base plate with many protruding protein tail fibres.
The poxviruses are large, complex viruses which possess 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. Covering the virus is an outer envelope with a thick layer of protein studded on its surface. The whole particle is slightly pleiomorphic, ranging from ovoid to brick shape. |
Size
The majority of viruses which have been studied have a
capsid diameter between 10 and 300
nanometres. To put viral size into perspective, a medium sized virion next to a flea is roughly equivalent to a human next to a mountain twice the size of Mount Everest. Some
filoviruses have a total length that can reach up to 1400 nm, however their capsid diametres are only about 80 nm. While most viruses are unable to be seen with a
light microscope, some are larger than the smallest bacteria and can be seen under high magification. Both scanning and transmission
electron microscopes are commonly employed to visualise virus particles.
A notable exception to the normal viral size range is the recently discovered
mimivirus, with a diameter of 400 nm. They also hold the record for the largest viral genome size, possessing about 1000 genes (some bacteria only possess 400) on a genome approximately 1.2
megabases in length. Their large genome also contains many genes which are
conserved in both prokaryotic and eukaryotic genes
[http://www.stanford.edu/group/virus/mimi/2005/Genome.htm]. The discovery of the virus has led many scientists to reconsider the controversial boundary between living organisms and viruses, which are currently considered as mere mobile genetic elements.
Genetic material
Both
DNA and
RNA are found in viral species, but generally a species will have either one or the otherâ€"not both. One exception is the human
cytomegalovirus, which contains both a DNA core and
mRNA. The nucleic acid can be either single-stranded or double-stranded, depending on the species. Therefore viruses as a group contain all four possible types of nucleic acids: double-stranded DNA, single-stranded DNA, double-stranded RNA and single-stranded RNA. Animal virus species have been observed to possess all combinations, whereas plant viruses tend to have single-stranded RNA. Bacteriophages tend to have double-stranded DNA. Also, the nucleic acids can be either linear or a closed loop.
Genome size in terms of the weight of
nucleotides varies quite substantially between species. The smallest genomes code for only four proteins and weigh about 10
6 daltons, while the largest weigh about 10
8 daltons and code for over one hundred proteins. Some virus species possess abnormal nucleotides, such as hydroxymethylcytosine instead of
cytosine, as a normal part of their genome.
For viruses with RNA as their nucleic acid, the strands are said to be either
positive-sense (also called plus-strand) or
negative-sense (also called minus-strand) depending on whether it is complementary to viral 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.
All double-stranded RNA genomes and some single-stranded RNA genomes are said to be segmented, or divided into separate parts. Each segment may code for one protein, and they are usually found together in one capsid. Not all segments are required to be in the same virion for the overall virus to be infectious, as can be seen in the
brome mosaic virus.
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. They may have a
lytic or a
lysogenic cycle, with some viruses are capable of carrying out both. A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed
cytopathic effects. Released virions can be passed between hosts through either direct contact, often via
body fluids, or through a
vector. In aqueous environments, viruses float free in the water.
In the lytic cycle, characteristic of virulent phages such as the
T4 phage, host cells will be induced by the virus to begin manufacturing the proteins necessary for virus reproduction. As well as proteins, the virus must also direct the replication of new genomes, the technique used for this varies greatly between virus species but depends heavily on the genome type. The final viral product is assembled spontaneously, though it may be aided by
molecular chaperones. After the genome has been replicated and the new capsid assembled, the virus causes the cell to be broken open (lysed) to release the virus particles. Some viruses do not lyse the cell but instead exit the cell via the
cell membrane in a process known as
exocytosis, taking a small portion of the membrane with them as a viral envelope. As soon as the cell is destroyed the viruses will have to find new host.
In contrast, the lysogenic cycle does not result in immediate lysing of the host cell, instead the viral genome integrates into the host DNA and replicates along with it. The virus remains dormant but after the host cell has replicated several times, or if environmental conditions permit it, the virus will become active and enter the lytic phase. The lysogenic cycle allows the host cell to continue to survive and reproduce, therefore the virus is passed on to all of the cell's offspring.
|
A falsely coloured electron micrograph of multiple bacteriophages |
Bacteriophages infect specific bacteria by binding to
surface receptor molecules and entering the cell. Within a short amount of time, sometimes 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 will be released.
Animal
DNA viruses, such as
herpesviruses, enter the host via
endocytosis, the process by which cells take in material from the external environment. This frequently occurs after chance collision with an appropriate surface receptor on a cell. After penetrating the cell, the viral genome is released from the capsid and host polymerases begin transcribing viral mRNA. New virions are assembled and released either by cell lysis or by budding off the cell membrane.
Animal
RNA viruses can be placed into about four different groups depending on their mode of replication. The
polarity of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded. Some
RNA viruses are actually DNA based but use a RNA-intermediate to replicate. RNA viruses are heavily dependent upon virally encoded
RNA replicase to create copies of their genomes.
A
reverse transcribing virus is any virus which replicates using reverse transcription, the formation of DNA from an RNA template. Those viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types of reverse transcribing viruses use the enzyme
reverse transcriptase to carry out the nucleic acid conversion.
Argument continues over whether viruses are truly alive or not. According to the
United States Code, they are considered to be
micro-organisms in the sense of biological weaponry and malicious use. Scientists however are more divided. They have no trouble classifying a horse as living and can see evolutionary relationships between it and other animals, but things become complicated as they look at the more simple viruses, viroids and prions. In the case of viruses, they resemble life in that they possess nucleic acid and can respond to their environment in a limited fashion. They can also reproduce by creating multiple copies of themselves through simple self-assembly.
However, unlike all other forms of established lifeforms, they do not possess a
cell structure, regarded as the basic unit of life. Viruses are also absent in the fossil record, making
phylogenic relationships difficult to infer. Additionally, although they reproduce they do not metabolise on their own and therefore require a host cell to replicate and synthesise new products. However, confounding this previous statement is the fact that bacterial species such as
Rickettsia and
Chlamydia, while living organisms, are also unable to reproduce outside of a host cell.
A powerful argument can be made that all accepted forms of life divide at the cell level via
cell division to reproduce, whereas all viruses simply assemble spontaneously within cells. What then prevents the comparison to be drawn that viral self-assembly is no different than the autonomous growth of non-living
crystals? Virus self-assembly within host cells also has implications for the study of the
origin of life, as it lends credence to the hypothesis that life could have started as self-assembling organic molecules.
Other questions involve the classification of viruses within the
Tree of Life and its implications â€" if viruses are considered alive, then the criteria specifying life will have been permanently changed, leading scientists to question what the basic prerequisite of life is. If they are considered living then the prospect of creating
artificial life is enhanced, or at least the standards required to call something artificially alive are reduced. Whether or not other infectious particles, such as
viroids and
prions, would next be considered forms of life could follow if viruses are said to be alive.
:''For more examples of diseases caused by viruses see
List of infectious diseasesExamples of common human diseases caused by viruses include the
common cold,
the flu,
chickenpox and
cold sores. Serious diseases such as
Ebola,
AIDS,
bird flu and
SARS are all also 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 Herpesvirus Six (HHV6) and neurological diseases such as
multiple sclerosis and
chronic fatigue syndrome. Recently it was also shown that cervical cancer is partially caused by
papillomavirus, representing evidence in humans of a link existing between cancer and an infective agent
[http://news.bbc.co.uk/2/hi/health/medical_notes/429762.stm]. There is current controversy over whether the
borna virus, previously thought of as causing
neurological disease in horses, could be responsible for
psychiatric illness in humans
[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=10089006&dopt=Abstract].
Viruses have many different mechanisms by which they produce disease in an organism, which largely depends on the 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 carry-on effects. Although many viruses result in the disruption of healthy
homeostasis, resulting in disease, they may reside relatively harmlessly within an organism. An example would include the ability of the
herpes simplex virus, which cause
coldsores, to remain in a dormant state within the human body.
Epidemics
A number of 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
[http://news.bbc.co.uk/2/hi/africa/4397891.stm].
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
[http://www.historylink.org/essays/output.cfm?file_id=5100]. The damage done by this disease may have significantly aided European attempts to displace or conquer the native population.
Detection, purification and diagnosis
In the laboratory, several techniques for growing and detecting viruses exist. Purification of viral particles can be achieved using
differential centrifugation,
isopycnic centrifugation, precipitation with
ammonium sulphate or
ethylene glycol, and removal of cell components from a homogenised cell mixture using
organic solvents or enzymes to leave the virus particles in solution.
Assays to detect and quantify viruses include:.
*
Hemagglutination assays, which quantitatively measure how many virus particles are in a solution of
red blood cells by the amount of
agglutination the viruses cause between them. This occurs as many viruses are able to bind to the surface of one or more red blood cells.
* Direct counts using an
electron microscope. A dilute mixture of virus particles and beads of known size are sprayed onto a special sheet and examined under high magnification. The virions are counted and the number extrapolated to estimate the number of virions in the undiluted mixture.
*
Plaque assays involve growing a thin layer of bacterial cells onto a culture dish and adding a dilute mixture of virions onto it. The virions will infect and kill the cells they land on, producing holes in the cell layer known as plaques. The number of plaques can be counted and the number of virions estimated from it.
Detection and subsequent isolation of new viruses from patients is a specialised laboratory subject. Normally it requires the use of large facilities, expensive equipment, and trained specialists such as technicians,
molecular biologists, and
virologists. Often, this effort is undertaken by state and national governments and shared internationally through organizations like the
World Health Organization.
Prevention and treatment
Because viruses use the machinery of a host cell to reproduce and also 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 drugs which treat the symptoms of viral infections. Patients often ask for, and
physicians often prescribe,
antibiotics. These are useless against viruses, and their misuse against viral infections is one of the causes of
antibiotic resistance in
bacteria. However, in life-threatening situations the prudent course of action is to begin a course of antibiotic treatment while waiting for test results to determine whether the patient's symptoms are caused by a virus or a bacterial infection.
Life sciences
Viruses 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. The study and use of viruses have provided valuable information about many aspects of cell biology. For example, viruses have simplified the study of
genetics and helped human understanding of the basic mechanisms of
molecular genetics, such as
DNA replication,
transcription,
RNA processing,
translation,
protein transport, and
immunology.
Geneticists regularly 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.
Materials science and nanotechnology
In April 2006 scientists at the
Massachusetts Institute of Technology (MIT) created
nanoscale metallic wires using a
genetically-modified virus
[http://web.mit.edu/newsoffice/2006/virus-battery.html]. The MIT team was able to use the virus to create a working
battery with an
energy density up to three times more than current materials. The potential exists for this technology to be used in
liquid crystals,
solar cells,
fuel cells, and other electronics in the future.
Weapons
The ability of viruses to cause devastating
epidemics in human societies has led to the concern that viruses could be weaponized for
biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory
[http://www.cdc.gov/OD/OC/MEDIA/pressrel/r051005.htm]. The
smallpox virus devastated numerous societies throughout history before its eradication. It currently exists in several secure laboratories in the world and fears that it may be stolen and used as a weapon are not totally unfounded. The modern global 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 was brought under control.
The word is from the
Latin virus referring to
poison and other noxious things, first used in English in 1392.
Virulent, from Latin
virulentus "poisonous" dates to 1400. A meaning of "agent that causes infectious disease" is first recorded in 1728, before the discovery of viruses by the
Russian-
Ukrainian biologist Dmitry Ivanovsky in 1892. The adjective
viral dates to 1948. Today,
Virus is used to describe the biological viruses discussed above and also as a metaphor for other parasitically-reproducing things, such as
memes or
computer viruses (since 1972). The
neologism virion or
viron is used to refer to a single infective viral particle.
The Latin word is from a
Proto-Indo-European root * "to melt away, to flow," used of foul or malodorous fluids. It is a cognate of
Sanskrit "poison,",
Avestan viš- "poison," Greek
ios "poison,"
Old Church Slavonic višnja "cherry,"
Old Irish fi "poison,"
Welsh gwy "fluid"; Latin
viscum (see
viscous) "sticky substance" is also from the same root.
The English plural form of
virus is
viruses. No reputable dictionary gives any other form, including such "reconstructed" Latin plural forms as
viri (which actually means
men), and no plural form appears in the Latin corpus (See
plural of virus). The word does not have a traditional Latin plural because its original sense,
poison is a
mass noun like the English word
furniture, and, as pointed out above, English use of
virus to denote the agent of a disease predates the discovery that these agents are microscopic parasites and thus in principle countable. Naturally this point can, and will, be extensively argued.
*
List of viruses*
Nanobes*
Nanobacteria*
Provirus*
Transduction*
WikiProject Viruses*
Chart of viral pathogens which contribute to indoor air pollution*
Viruses: The new cancer hunters - An IsraCast article on virotherapy
*
The Big Picture Book of Viruses - Pictures and general information on many viruses
*
Scientific American Magazine (October 2003 Issue) Tumor-Busting Viruses*
Detailed genomic and bioinformatic information about Category A, B, and C priority pathogens at NIH-funded database.
