A virus (from the Latin noun virus, meaning toxin or poison) is a sub-microscopic particle (ranging in size from about 15–600 nm) that can infect the cells of a biological organism. Viruses can replicate themselves only by infecting a host cell. They therefore can't reproduce on their own. At the most basic level, viruses consist of genetic material contained within a protective protein coat called a capsid. They infect a wide variety of organisms: both eukaryotes (animals, plants, protists, and fungi) and prokaryotes (bacteria and archaea). A virus that infects bacteria is known as a bacteriophage, often shortened to phage. The study of viruses is known as virology and people who study viruses are known as virologists. Viruses cause several serious human diseases, such as AIDS, influenza and rabies. Therapy is difficult for viral diseases as antibiotics have no effect on viruses and antiviral drugs are expensive. The best way to prevent viral diseases is with a vaccine, which produces immunity.
It has been argued extensively whether viruses are living organisms. Most "plant" virologists, and those who study bacteriophages consider them non-living as they don't meet all the criteria of the generally accepted definition of life. For example, unlike most organisms as defined, viruses don't consist of cells, generally regarded as the fundamental unit of life. Whereas most "animal" virologists consider them as living because they've genes and evolve by natural selection.
Discovery
Viral diseases such as rabies, yellow fever and smallpox have affected humans for many centuries. There is hieroglyphical evidence of polio in the ancient Egyptian empire, though the cause of these diseases was unknown at the time. In 1717, Mary Montagu, the wife of an English ambassador to the Ottoman Empire, observed local women inoculating their children against smallpox. In the late 18th century, Edward Jenner observed and studied Miss Sarah Nelmes, a milkmaid who had previously caught cowpox and was subsequently found to be immune to smallpox, a similar, but devastating virus. Jenner developed the first vaccine based on these findings; after lengthy (but successful) vaccination campaigns the World Health Organization (WHO) certified the eradication of smallpox in 1979.
In the late 19th century Charles Chamberland developed a porcelain filter with pores small enough to filter bacteria, yet retain all viable viruses. Dimitri Ivanovski used this filter to study tobacco mosaic virus. He published experiments showing that crushed leaf extracts of infected tobacco plants were still infectious after filtering through such filters. At about the same time, several others documented filterable disease-causing agents, with several independent experiments showing that viruses were different from bacteria, yet they could also cause disease in living organisms. These experiments showed that viruses are orders of magnitudes smaller than bacteria. The term virus was coined by the Dutch microbiologist Martinus Beijerinck.
In the early 20th century, Frederick Twort discovered that bacteria could be attacked by viruses. Felix d'Herelle, working independently, showed that a preparation of viruses caused areas of cellular death on thin cell cultures spread on agar. Counting the dead areas allowed him to estimate the original number of viruses in the suspension. The invention of Electron microscopy provided the first look at viruses. In 1935 Wendell Stanley crystallised the tobacco mosaic virus and found it to be mostly protein. A short time later the virus was separated into protein and nucleic acid parts. In 1939, Max Delbrück and E.L. Ellis demonstrated that, in contrast to cellular organisms, bacteriophage reproduce in "one step", rather than exponentially.
A major problem for early virologists was the inability to propagate viruses on sterile culture media, as is done with cellular microorganisms. This limitation required medical virologists to infect living animals with infectious material, which is dangerous. The first breakthrough came in 1931, when Ernest William Goodpasture demonstrated the growth of influenza and several other viruses in fertile chicken eggs. However, many viruses wouldn't grow in chicken eggs, and a more flexible technique was needed for propagation of viruses. The solution came in 1949 when John Franklin Enders, Thomas H. Weller and Frederick Chapman Robbins together developed a technique to grow polio virus in cultures of living animal cells. Their methods have since been extended and applied to the growth of many viruses and other infectious agents that don't grow on sterile culture media.
Origins
The origins of modern viruses are not entirely clear. It may be that no single mechanism can account for the orgins of all viruses. They don't fossilize well, so molecular techniques have been the most useful means of hypothesising how they arose. Research in microfossil identification and molecular biology may yet discern fossil evidence dating to the Archean or Proterozoic eons. Two main hypotheses currently exist.
Small viruses with only a few genes may be runaway stretches of nucleic acid originating from the genome of a living organism. Their genetic material could have been derived from transferable genetic elements such as plasmids or transposons, that are prone to moving within, leaving, and entering genomes. New viruses are emerging de novo all the time and it isn't the case that all viruses have "ancestors"
Viruses with larger genomes, such as poxviruses, may have once been small cells which parasitised larger host cells. Over time, genes not required by their parasitic lifestyle would have been lost in a streamlining process known as retrograde-evolution or reverse-evolution. The bacteria Rickettsia and Chlamydia are living cells that, like viruses, can only reproduce inside host cells. They lend credence to the streamlining hypothesis, as their parasitic lifestyle is likely to have caused the loss of genes that enabled them to survive outside a host cell.
It is possible that viruses represent a primitive form of self replicating DNA and are a precursor to life as it's presently defined.
Other infectious particles which are even simpler in structure than viruses include viroids, satellites, and prions.
Classification
In
taxonomy, the classification of viruses is difficult owing to the lack of a fossil record and the dispute over whether they're living or non-living. They don't fit easily into any of the
domains of
biological classification and therefore classification begins at the
family rank. However, the domain name of
Acytota (without cells) 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 distinguish 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.
Structure
A complete virus particle, known as a
virion, consists, in its simplest form, 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 subunits - sometimes called
protomers - will self-assemble to form the capsid, generally requiring the presence of the virus genome - however, many complex viruses code for proteins which 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.
In general, there are four main morphological virus types:
| Image |
Helical viruses |
|
Helical capsids are composed of a single type of subunit 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 anything from short and highly rigid, to long and very flexible. The genetic material - generally single-stranded RNA, but also ssDNA in the case of certain phages - is bound into the protein helix, by charge 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, while the diameter is dependent on the size and arrangement of protomers. The well-studied Tobacco mosaic virus is an example of a helical virus. |
| Image |
Icosahedral viruses |
|
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're 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 or more protomers.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, 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.
|
| Image |
Enveloped viruses |
|
In addition to a protein capsid many viruses are able to envelope themselves in a modified form of one of the cell membranes - the outer membrane surrounding an infected host cell, or from 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; however the lipid membrane itself and any carbohydrates present are entirely host-coded. The Influenza virus and HIV use this strategy.
The viral envelope can give a virion a few distinct advantages over other capsid-only virions, such as protection from enzymes and certain chemicals. The proteins in it can include glycoproteins functioning as receptor molecules, allowing host cells to recognise and bind these virions, resulting in the possible uptake of the virion into the cell. Most enveloped viruses are dependent upon the envelope for infectivity.
|
| Image |
Complex viruses |
|
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 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. |
Size
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 of up to 1400 nm, however their capsid diameters are only about 80 nm. The majority of viruses which have been studied have a
capsid diameter between 10 and 300
nanometres. While most viruses are unable to be seen with a
light microscope, some are as large or larger than the smallest bacteria and can be seen under high optical magnification. More commonly, both scanning and transmission
electron microscopes are used to visualise virus particles.
A notable exception to the normal viral size range is the recently discovered
mimivirus, with a diameter of 750 nm which is larger than a
Mycoplasma bacterium. 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. 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.
Genome
| Property |
Parameters |
| Nucleic acid |
|
| Shape |
Linear
Circular
Segmented
|
| Strandedness |
Single-stranded
Double-stranded
Double-stranded with regions of single-strandedness
|
| Sense |
Positive 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.
Nucleic acid
A virus may employ either
DNA or
RNA as the nucleic acid. Rarely do they contain both, however
cytomegalovirus is an exception to this, possessing a DNA core with several
mRNA segments. By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA. Some virus species possess abnormal
nucleotides, such as
hydroxymethylcytosine instead of
cytosine, as a normal part of their genome.
A clue as to what type of nucleic acid the virus has can often, but not always, be found in the virus's name. Pico
rnaviruses, (such as
Poliovirus and
Foot-and-mouth virus) have
RNA as do Co
ronaviruses. Hepatitis B virus is an Hepa
dnavirus and has
DNA. Picobi
rnaviruses have two segments of RNA.
Shape
Viral genomes may be 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 may be divided up into separate parts within the virion, or
segmented. All double-stranded RNA genomes, and some single-stranded RNA genomes, are segmented, (see below). Each segment may code for one protein, and they're 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 demonstrated by the
brome mosaic virus.
Strandedness
A viral genome, irrespective of nucleic acid type, may be 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 2 complimentary paired nucleic acids, analogous to a ladder. Some viruses, such as those belonging to the
Hepadnaviridae, contain a genome which is partially double-stranded and partially single-stranded. Viruses that infect humans include double-stranded RNA (eg.
Rotavirus), single-stranded RNA (eg.
Influenza virus), single-stranded DNA (eg.
Parvovirus B19) and double-stranded DNA (
Herpes virus).
Sense
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's 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. 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 (+).
Genome size
Genome size in terms of the weight of
nucleotides varies 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.
RNA viruses generally have smaller genome sizes than
DNA viruses due to a higher error-rate when replicating, resulting in a maximum upper size limit. Beyond this limit, too many errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, many RNA viruses have segmented genomes where the genome is split into smaller molecules, thus reducing the chances for errors. In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes.
The rotavirus genome consists of 11 segments of double-stranded RNA. In this photograph, the genes from six strains of rotavirus have been separated by electrophoresis and stained with ethidium bromide and photographed under ultraviolet light.
Gene Reassortment
There is also an evolutionary advantages in having a segmented genome. Different strains of a virus with a segmented genome, from a pig or a bird or a human for example, such as
Influenza virus can shuffle and mix each others genes producing progeny viruses (offspring) that have unique characteristics. This is called reassortment or
viral sex.. This is one reason why Influenza viruses are constantly changing.
Genetic Change
Viruses undergo genetic change by several mechanisms:
• 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 don't change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to
antiviral drugs.
• A process called
antigenic shift where there's a major change in the
genome of the virus. This occurs as a result of
recombination or
reassortment (see above). When this happens with
influenza viruses major
pandemics can result.
• By genome rearrangement where the structure of the gene changes although no mutations have necessarily occurred.
RNA viruses are much more mutable than DNA viruses for the reasons outlined above. Furthermore, viruses often exist as
quasispecies or swarms of viruses of the same species but all with slightly different genome nucleoside sequences. Such quasispecies are a prime target for
natural selection.
Replication
Viral populations don't grow through
cell division, because they're acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves. 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.
Virus Life Cycle
There are five stages in the life cycle of viruses:
1. Attachment
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 instance, the human immunodeficiency virus (
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 that they're capable of replicating in.
2. Penetration
Following attachment, viruses enter the host cell through receptor mediated
endocytosis or other mechanisms.
3. Uncoating
Uncoating is a process that viral
capsid is removed is degraded by viral
enzymes or host enzymes thus releasing the viral genomic nucleic acid.
4. Replication
Replication involves synthesis of viral messenger RNA (
mRNA) for all viruses except postive 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-translation modification of the viral proteins often occurs.
5.Release
Viruses are released from the host cell by lysis (see below) . Enveloped viruses (for example, HIV) typically are released from the host cell by “budding”. During this process, the virus acquires its phospholipid envelope which contain embedded viral glycoproteins.
Lytic or lysogenic
Viruses may have a
lytic or a
lysogenic cycle, with some viruses capable of carrying out both.
Lytic cycle
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 don't 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 have to find a new host.
Lysogenic cycle
In contrast, the lysogenic cycle doesn't 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, and the virus is passed on to all of the cell’s offspring.
Bacteriophages
Bacteriophages infect specific bacteria by binding to
surface receptor molecules and then enter 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.
DNA viruses
Animal
DNA viruses, such as
herpesviruses, enter the host via
endocytosis, the process by which cells take in material from the external environment. Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates 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.
RNA viruses
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 an RNA-intermediate to replicate. RNA viruses are heavily dependent upon virally encoded
RNA replicase to create copies of their genomes.
Reverse transcribing viruses
Reverse transcribing viruses are viruses that replicate using reverse transcription, which is 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
reverse transcriptase enzyme to carry out the nucleic acid conversion and are susceptible to
antiviral drugs designed to inhibit the enzyme, e.g
zidovudine and
lamivudine.
An example of the first type is
HIV which is a
retrovirus. Retroviruses often integrate the DNA produced by
reverse transcription into the host genome. This is why HIV infection can at present, only be treated and not cured.
Examples of the second type are the
Hepadnaviridae which includes
Hepatitis B virus and the
Caulimoviridae - for example
Cauliflower mosaic virus.
Lifeform debate
Viruses have been described as
organisms at the edge of life but argument continues over whether viruses are truly alive. According to the
United States Code, they're considered
microorganisms in the sense of biological weaponry and malicious use. Scientists, however, are divided. Things become more complicated as they look at
viroids and
prions. Viruses resemble other organisms in that they possess genes, and can evolve - in infected cells - by
natural selection
They can also reproduce by creating multiple copies of themselves through self-assembly.
Viruses don't have a
cell structure, regarded by some as the basic unit of life although they do have genes. Additionally, although they reproduce, they don't metabolise on their own and therefore require a host cell to replicate and synthesise new products. However, some bacterial species such as
Rickettsia and
Chlamydia, while considered to be living organisms, are also unable to reproduce outside of a host cell.
An argument can be made that all accepted forms of life use
cell division to reproduce, whereas all viruses spontaneously assemble within cells. The comparison is drawn between viral self-assembly and 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.
If viruses are considered alive, then the criteria specifying life will have to exclude the cell. If viruses are said to be alive, the question could follow of whether even smaller infectious particles, such as
viroids and
prions, are also alive.
Viruses and disease
» For more examples of diseases caused by viruses see List of infectious diseases
Examples of common human diseases caused by viruses include the
common cold,
the flu,
chickenpox and
cold sores. Many serious diseases such as
Ebola,
AIDS,
avian flu and
SARS are 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. 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.
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 effects. Although many viruses result in the disruption of healthy
homeostasis, resulting in disease, they may also exist 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. This is called latency and is a characteristic of all the
herpes viruses including
Epstein-Barr virus which causes glandular fever and
Varicella zoster virus which causes
chicken pox. Latent chickenpox infections return in later life as the disease called
shingles.
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.
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 may have significantly aided European attempts to displace or conquer the native population.
Viruses and Cancer
Viruses are an established cause of
malignancy in humans and many other species.
The main viruses associated with human cancers are
human papillomavirus,
hepatitis B and
hepatitis C virus,
Epstein-Barr virus, and
human T-lymphotropic virus.
Hepatitis viruses, including
hepatitis B and
hepatitis C, can induce a chronic viral infection that leads to
liver cancer.
Human T-lymphotropic viruscauses Tropical Spastic Paraparesis and Adult T-cell leukaemia
Human papillomaviruses cause cancers of cervix, skin, anus, penis.
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 disease and
Nasopharyngeal carcinoma.
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 sulfate 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 host 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 infectious virions is estimated from it. Importantly, unlike other assays, the plaque assay is the only method that can accurately assess the number of infectious virus particles in a preparation of virus. Notably, most viruses exhibit low particle to PFU (plaque forming units) ratios - HIV is famous for this,; for example often hundreds or thousands of defective particles are generated for each one that can actually productively replicate in a permissive cell.
PCR and other nucleic amplification methods. This method is used for measuring the amount of a virus in blood and is called a viral load. It is used to monitor people who are being treated with antiviral drugs.
Laboratory Diagnosis
In the diagnostic laboratoy virus infections are confirmed by several methods that include:
Growth of the virus in a cell culture from a specimen taken from the patient.
Detection of virus-specific IgM antibody (see below) in the blood.
Detection of virus antigens by EIA in tissues and fluids.
Detection of virus encoded DNA and RNA by PCR.
Observation of virus particles by electron microscopy.
Prevention and treatment
Because viruses use the machinery of a host cell to reproduce and also reside within them, they're 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 which treat the symptoms of viral infections.
Host Immune Response
When the immune system of a vertebrate encounters a virus, it produces specific antibodies which 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. Both types of antibodies are measured when tests for immunity are carried out.
A second defense 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 recognizes 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.
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 also evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift.
The production of interferon is also an important host defense mechanism.
When many viruse reproduce in the cell the produce dsRNA molecules. A cascade of interacting enzymes detects these RNAs and then proceeds to destroy all single-stranded copies. This is called RNA interference, and it's an important cellular mechanism found in plants, animals and many other eukaryotes, and has most likely evolved as a defense against viruses.
Vaccines
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 as resulted in a dramatic decline in morbidity and mortality associated with viral infections such as measles, mumps and rubella and smallpox infections have been eradicated. Currently vaccines are available to prevent over thirteen viral infections of humans and many more are used to prevent viral infections of animals.
Antiviral Drugs
Over the past twenty years the development of antiviral drugs has increased rapidly. This has been driven by the AIDS epidemic. Many antiviral drugs are 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. Examples of nucleoside analogues are aciclovir for Herpes virus infections and lamivudine for HIV and Hepatitis B virus infections. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called protease for it to become fully infectious. There is a class of drugs called protease inhibitors which have been designed to inactivate the enzyme.
Hepatitis C is caused by an RNA virus. In 80% of people infected the disease is chronic and without treatment they're infected and infectious for the remainder of their lives. However, there's now an effective treatment using the nucleoside analogue drug ribavirin combined with interferon The treatment of chronic carriers of the Hepatitis B virus by using a similar strategy using lamivudine is being developed.
Potential uses in therapy
Virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promise in the treatment of cancer and as a method for gene therapy. Eastern European doctors 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.
Applications
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're 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
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.
In April 2006 scientists at the Massachusetts Institute of Technology (MIT) created nanoscale metallic wires using a genetically-modified virus. 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. 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 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 is brought under control.
Etymology
The word is from the Latin virus referring to poison and other noxious substances, 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, 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).
Electron Micrographs of Viruses
Image:Norwalk.jpg|Norovirus. This RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals.
Image:Caliciviruses2.jpg|Caliciviruses are related to Noroviruses.
Image:Human Torovirus.jpg|Torovirus. An enveloped RNA virus.
Image:Coronaviruses 004 lores.jpg|Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope.
Image:Ebola virus.jpg|Ebola Virus is a filamentous RNA virus.
Image:Measles virus.JPG|Measles virus. This is called a thin section where the virus particle has been cut in two.
Image:Respiratory syncytial virus 01.jpg|Respiratory Syncytial Virus (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern.
Image:Parvovirus in Blood.jpg|Parvovirus B19. Parvovirus B19 is a small DNA virus best known for causing a childhood exanthema called fifth disease or erythema infectiosum.
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