Virus

This article is concerned with virus as a biological infectious particle; for other uses see virus (disambiguation).

File:Aids virus.jpg

The human immunodeficiency virus (HIV)

A virus is a microscopic parasite that infects cells in biological organisms. Viruses are obligate intracellular parasites; they can reproduce only by invading and controlling other cells as they lack the cellular machinery for self-reproduction. The term virus usually refers to those particles that infect eukaryotes (multi-celled organisms and many single-celled organisms), whilst the term bacteriophage or phage is used to describe those infecting prokaryotes (bacteria and bacteria-like organisms lacking a nucleus). Typically these particles carry a small amount of nucleic acid (either DNA or RNA, but not both) surrounded by some form of protective coat consisting of proteins, lipids, glycoproteins or a combination. Importantly, viral genomes code not only for the proteins needed to package its genetic material, but for proteins needed by the virus during its life cycle (the term "life cycle" is used loosely here—see Living or non-living?).

Origins and Beginnings

The origins of viruses are not entirely clear and there may not be a single mechanism that can account for all viruses. Some of the smaller viruses that have only a few genes may have originated from host organisms. Their genetic material could have been derived from transferrable elements like plasmids or transposons. Viruses with large genomes may represent extremely reduced microbes which established symbiotic relations with host organisms, allowing the loss of some genes needed for existence independent of a host.

Other infectious particles which are even simpler in structure than viruses include viroids, virusoids, and prions.

Size, structure, and anatomy

Virus particles comprise a nucleic acid genome that may be either DNA or RNA, single- or double-stranded, and positive or negative sense. This is surrounded (encapsidated) by a protective coat of protein called a capsid. The viral capsid may be either spherical or helical and is composed of proteins encoded by the viral genome. In helical viruses, the capsid protein (frequently called the nucleocapsid protein) binds directly to the viral genome. For example, in the case of the measles virus, one nucleocapsid protein binds every six bases of RNA to form a helix approximately 1.3 micrometers in length. This complex of protein and nucleic acid is called the nucleocapsid, and, in the case of the measles virus, is enclosed in a lipid "envelope" acquired from the host cell, in which virus-encoded glycoproteins are embedded. These are responsible for binding to and entering the host cell at the start of a new infection. Spherical virus capsids completely enclose the viral genome and do not generally bind as tightly to the nucleic acid as helical capsid proteins do. These structures can range in size from less than 20 nanometers up to 400 nanometers and are composed of viral proteins arranged with icosahedral symmetry. Icosahedral architecture is the same principle employed by R. Buckminster-Fuller in his geodesic dome, and it 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" whereby 60t proteins are necessary. In the case of the hepatitis B virus, the T-number is 4, therefore 240 proteins assemble to form the capsid. As in the helical viruses, the spherical virus capsid may be enclosed in a lipid envelope, although frequently spherical viruses are not enveloped, and the capsid proteins themselves are directly involved in attachment and entry into the host cell. The complete virus particle is referred to as a virion. A virion is little more than a gene transporter, and components of the envelope and capsid provide the mechanism for injecting the viral genome into a host cell.^[1].

Replication

Because viruses are acellular and do not have their own metabolism, they must utilize the machinery and metabolism of the host to reproduce. Before a virus has entered a host cell, it is called a virion — a package of viral genetic material. Virions can be passed from host to host either through direct contact or through a vector, or carrier. Inside the organism, the virus can enter a cell in various ways. Bacteriophages—bacterial viruses—attach to the cell wall surface in specific places. Once attached, enzymes make a small hole in the cell wall, and the virus injects its DNA into the cell. Other viruses (such as HIV) enter the host via endocytosis, the process whereby cells take in material from the external environment. After entering the cell, the virus's genetic material begins the destructive process of causing the cell to produce new viruses.

There are three different ways genetic information contained in a viral genome can be reproduced. The form of genetic material contained in the viral capsid, the protein coat that surrounds the nucleic acid, determines the exact replication process.

Some viruses have DNA, which once inside the host cell is replicated by the host along with its own DNA.

There are two different replication processes for viruses containing RNA. In the first process, the viral RNA is directly copied using an enzyme called RNA replicase. This enzyme then uses that RNA copy as a template to make hundreds of duplicates of the original RNA. A second group of RNA-containing viruses, called the retroviruses, uses the enzyme reverse transcriptase to synthesize a complementary strand of DNA so that the virus's genetic information is contained in a molecule of DNA rather than RNA. The viral DNA can then be further replicated using the resources of the host cell.

Outline

1. Attachment, sometimes called absorption: The virus attaches to receptors on the host cell wall.
2. Injection: The nucleic acid of the virus moves through the plasma membrane and into the cytoplasm of the host cell. The capsid of a phage, a bacterial virus, remains on the outside. In contrast, many viruses that infect animal cells enter the host cell intact.
3. Replication: The viral genome contains all the information necessary to produce new viruses. Once inside the host cell, the virus induces the host cell to synthesize the necessary components for its replication.
4. Assembly: The newly synthesized viral components are assembled into new viruses.
5. Release: Assembled viruses are released from the cell and can now infect other cells, and the process begins again.

When the virus has taken over the cell, it immediately causes the host to begin manufacturing the proteins necessary for virus reproduction. Some viruses, like herpes, cause the host to produce three kinds of proteins: early proteins, enzymes used in nucleic acid replication; late proteins, proteins used to construct the virus coat; and lytic proteins, enzymes used to break open the cell for viral exit. The final viral product is assembled spontaneously, that is, the parts are made separately by the host and are joined together by chance. This self-assembly is often aided by molecular chaperones, or proteins made by the host that help the capsid parts come together.

The new viruses then leave the cell either by exocytosis or by lysis. Envelope-bound animal viruses cause the host's endoplasmic reticulum to make certain proteins, called glycoproteins, which then collect in clumps along the cell membrane. The virus is then discharged from the cell at these exit sites, referred to as exocytosis. On the other hand, bacteriophages must break open, or lyse, the cell to exit. To do this, the phages have a gene that codes for an enzyme called lysozyme. This enzyme breaks down the cell wall, causing the cell to swell and burst. The new viruses are released into the environment, killing the host cell in the process.

Lifeform debate

A virus makes use of existing host enzymes and other molecules of a host cell to create more virus particles (virions). Some viruses encode part or all of their own genome replication machinery and are not entirely reliant on host polymerases for replication of their genetic material. Such viruses can be targeted by antiviral drugs that specifically inhibit the virally encoded replicase molecule(s). Viruses rely on host cell ribosomes for the production of viral proteins and utilize several distinct strategies to make the host cell synthesize the viral proteins. For example, at least some +RNA viruses use Internal Ribosome Entry Site IRES segments to drive the translation from their genomic +RNA molecule. Viruses are neither unicellular nor multicellular organisms; they are somewhere between being living and non-living. Viruses have genes and show inheritance, but are reliant on host cells to produce new generations of viruses. Many viruses have similarities to complex molecules. Because viruses are dependent on host cells for their replication they are generally not classified as "living". Whether they are "alive", they are obligate parasites, and have no form which can reproduce independently of their host. Like most parasites, they have a specific host range, sometimes specific to one species (or even limited cell types of one species) and sometimes more general.

Some viruses form by self-assembly of protein and nucleic acid molecules. These macromolecules are assembled within host cells from smaller organic compounds. Virus self-assembly has implications for the study of the origin of life. Some viruses also incorporate lipids from the host cell membrane when their core protein-nucleic acid complex buds from the surface of a host cell. Concerning whether viruses are alive or not, if the requirement for autonomous self-reproduction is abandoned, it can be argued strongly that viruses are indeed alive. Some small viruses are more efficient than most cellular life forms as their ratio of functions to working parts is so high. If viruses are alive then the prospect of creating artificial life is enhanced or at least the standards required to call something artificially alive are reduced.

Study and applications

Exploring basic cellular processes

Viruses are important to the study of molecular and cellular biology because 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 further simplified the study of genetics and have deepened our understanding of the basic mechanisms of molecular genetics (DNA replication, transcription, RNA processing), Translation (genetics), protein transport, and immunology.

Genetic engineering

Geneticists regularly use viruses as vectors to introduce genes into cells that they are studying. Attempts to treat human diseases through the use of viruses as tools of genetic engineering is one goal of gene therapy.

Materials science and nanotechnology

Scientists at MIT have recently been able to use viruses to create metallic wires, and they have the potential to be used for binding to exotic materials, self-assembly, liquid crystals, solar cells, batteries, fuel cells, and many other interesting areas.

The essential idea is to use a virus with a known protein on its surface. The location of the code for this protein is in a known location in the DNA, and by randomizing that sequence it can create a phage library of millions of different viruses, each with a different protein expressed on its surface. By using natural selection, one can then find a particular strain of this virus which has a binding affinity for a given material.

For example, one can isolate a virus which has a high affinity for gold. Taking this virus and growing gold nanoparticles around it results in the gold nanoparticles being incorporated into the virus coat, resulting in a gold wire of precise length and shape with biological origins.

Current thinking is that viruses will one day be created which can act as agents on behalf of bio-mechanical healing devices giving humans or other animals extended life.

Human viral diseases

Examples of diseases caused by viruses include the common cold, which is caused by any one of a variety of related viruses; smallpox; AIDS, which is caused by HIV; and cold sores, which are caused by herpes simplex. Other connections are being studied such as the connection of HHV-6 in organic neurological diseases such as Multiple Sclerosis and Chronic Fatigue Syndrome. Recently it has been shown that cervical cancer is caused at least partly by papillomavirus (which causes papillomas, or warts), representing the first significant evidence in humans for a link between cancer and an infective agent. There is current controversy over whether borna virus, previously thought of primarily as the causative agent of neurological disease in horses, could be responsible for psychiatric illness in humans. The relative ability of viruses to cause disease is described in terms of virulence.

The ability of viruses to cause devastating epidemics in human societies has led to concern that viruses will be weaponized for biological warfare. Further concern was raised by the successful recreation of a virus in a laboratory. Much concern revolves around the smallpox virus, which has devastated numerous societies throughout history, and today is extinct in the wild. In fact, smallpox has been used in a crude form of biological warfare by British colonists against a tribe of Native Americans.

This episode of biological warfare was part of a larger phenomenon of Native American populations being devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by smallpox after the arrival of Columbus in the Americas, but it may have been very large. The damage done by this disease may have significantly aided European attempts to displace or conquer the native population. Jared Diamond argued in his book Guns, Germs, and Steel that highly contagious diseases develop in agricultural societies and regularly aid those societies when they expand into the territories of non-agricultural peoples.

Of all types of virus, the most deadly are known as filovirus. The Filovirus group consists of Marburg, first discovered in 1967 in Marburg Germany, and ebola. Filovirus are long, worm-like virus particles that, in large groups, resemble a plate of noodles. As of April 2005, the Marburg virus is attracting widespread press attention for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak, which now appears to be coming under control, is the world's worst epidemic of any kind of hemorrhagic fever.

Laboratory diagnosis of pathogenic viruses

Detection and subsequent isolation of viruses from patients is a very specialised laboratory subject. Normally it requires the use of large facilities, expensive equipment, and highly 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 WHO.

Prevention and treatment of viral diseases

Because they use the machinery of their host cells to reproduce, viruses are difficult to kill. The most effective medical approaches to viral diseases, thus far, are vaccination to provide resistance to infection, and drugs that treat the symptoms of viral infections. Patients often ask for antibiotics, which are useless against viruses, and their misuse against viral infections is one of the causes of antibiotic resistance in bacteria. That said, sometimes, 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.

Etymology

Although the viruses were discovered by the Russian biologist Dmitry Ivanovsky in 1892, the name for them was coined later. The original word comes from the Latin virus referring to poison and other noxious things. Today it 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. The word virion or viron is used to refer to a single infective viral particle.

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). (No plural form appears in any extant Latin manuscript). (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.

See also

• Horizontal gene transfer
• List of viruses
• Microbiology
• Prion
• Viral plaque
• Viroids
• Virology
• Virus classification

See also

• Wikipedia:WikiProject Viruses
• WikiSpecies:Virus
• Wiktionary:en:virus

References

• All the Virology on the WWW
• Radetsky, Peter (1994). The Invisible Invaders: Viruses and the Scientists Who Pursue Them. Backbay Books, ISBNs 0316732168 (hc), 0316732176 (pb).
• Theiler, Max and Downs, W. G. (1973). The Arthropod-Borne Viruses of Vertebrates: An Account of the Rockefeller Foundation Virus Program 1951-1970. Yale University Press.
•  This article incorporates public domain material from Science Primer. NCBI. Archived from the original on 2009-12-08.
• Chronic Active Human Herpesvirus-6 (HHV-6) Infection: A New Disease Paradigm - Joseph H. Brewer, M.D. http://www.plazamedicine.com/index.html

Numbered references

1. ^ Gelderblom, Hans R. (1996). 41. Structure and Classification of Viruses in Medical Microbiology 4th ed. Samuel Baron ed. The University of Texas Medical Branch at Galveston. ISBN 0963117211