Virus

A virus is a submicroscopic parasite that infects cells in biological organisms. Viruses are obligate intracellular parasites; they can reproduce only by invading and controlling cells as they lack the cellular machinery for self-reproduction. Viruses infect eukaryotes and prokaryotes such as bacteria; viruses infecting prokaryotes are also known as bacteriophages or phages. Typically viruses carry a small amount of genetic material, either in the form of DNA or RNA, but not both, surrounded by some form of protective coat consisting of proteins, lipids, glycoproteins or a combination. The viral genome codes for the proteins that constitute this protective coat, as well as for those proteins required for viral reproduction that are not provided by the host cell.

Origins

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 with established symbiotic relations with host organisms, allowing the loss of some genes needed for existence independent of a host.

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

Size, structure, and anatomy

A virus particle, known as a virion, is little more than a gene transporter, consisting at the most basic level of a genome contained within a protective casing of protein. The nucleic acid genome varies among different viruses and may be either DNA, RNA, or both, single- or double-stranded, linear or circular, and positive or negative sense. The genetic material is surrounded and thus encapsidated by a protective coat of protein called a capsid. This capsid is composed of proteins encoded by the viral genome and may be either spherical or helical. These proteins are associated with the nucleic acid and are hence known as nucleoproteins, the combined partnership of nucleoproteins and nucleic acid producing what is known as a nucleocapsid.

In addition to a capsid some viruses are able to hijack a modified form of the plasma membrane surrounding an infected host cell, thus gaining an outer lipid bilayer known as a viral envelope. This extra membrane is studded with proteins synthesized by the host cell, which the virus may have modified at a genetic level. This gives the virion a few distinct advantages over "naked" virions - the plasma membrane provides a degree of protection for the virus, especially from harmful agents such as enzymes and chemicals. The proteins studded upon it include glycoproteins, which serve as receptor molecules, allowing healthy cells to recognise virions as "friendly" and resulting in the possible uptake of the virion into the cell.

Helical capsids are composed of identical proteins stacked at a constant amplitude and pitch to one another around a central circumference, much like a spiral staircase, which effectively forms an enclosed tube housing the genetic material. This arrangement results in rod-shaped virions which can either be short and rigid or long and flexible; the nature of long helical particles neccessitates flexibility, as they are prone to damage if they are too rigid.

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, hence are not truly "spherical". 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", where 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. Many spherical viruses forgo a lipid envelope, leaving the capsid proteins to be directly involved in attachment and entry into the host cell.

Replication

Because viruses are acellular and do not have their own metabolism, they must utilize the machinery and metabolism of the host for the purpose of self-replication. 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 by which 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.

Bacteriophages have two cycles called the lytic and lysogenic cycle. In the lytic cycle the host cell undergoes lysis (the breaking open of the cell to release viral particles), Biosynthesis, Maturation and finally release. In the lysenogenic cycle viral replication does not immediately occur, but replication may take place some time in the future. some viruses e.g. lambda are capable of carrying out both cycles. In the lytic cycle the cell is soon destroyed and the viruses made will have to find new host. However during the lysogenic stage the DNA of the bacteria is spliced using restriction enzymes and the viruses DNA (or RNA turned to DNA by the enzyme reverse transcriptase) is integrated into the spliced section of the hosts DNA. The virus remains dormant but after the host cell has replicated many times the virus will become active and will enter the lytic phase. The lysogenic cycle allows the host cell to continue to survive and reproduce. As the host reproduces with the virus embedded in its genome, the virus itself is reproduced as a byproduct. Therefore many progeny cells containing the virus develop.

Population growth

Viral populations do not grow through cell division (local doubling), but instead each infected cell becomes a virus factory that is capable of producing thousands of copies of the invading viruses.

Lifecycle

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 helped human understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology.

Viro-therapy

Viro-therapy uses viruses as treatment against various diseases, most commonly as a vector. It is not a new idea. In treatments in oncology for example, it was recognized as early as the mid 20th Century, when a number of physicians noticed an interesting phenomenon: some of their patients, who suffered from cancer and had an incidental viral infection, or subjected to vaccination, improved, experiencing a remission from their symptoms. In the 1940s and 1950s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors, and in 1956, one of the first human clinical trials with oncolytic viruses was conducted in patients with advanced-stage cervical cancer. Nevertheless, systematic research of this field was delayed for years, due to lack of more advanced technologies. In recent years the research in the field of oncolytic viruses began to move forward more quickly and Researchers are trying new ways to use viruses for the therapeutic benefit of patients.

In 2006 Researchers from the Hebrew University have succeeded in isolating a variant of the Newcastle disease Virus (NDV-HUJ), which usually affects birds, in order to specifically target cancer cells [1]. The researchers tested the new Viro-therapy on Glioblastoma multiforme patients and achieved promising results for the first time.

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 the Massachusetts Institute of Technology (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 other electronics.

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 Human Herpesvirus Six ( HHV6 one of the eight known members of the human herpesvirus family) 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.

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 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.

A number of highly lethal viral pathogens are members of the Filoviridae. 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.

A new type of virus discovered in 2003 has been termed mimivirus ("mimic virus") for its resemblance, in some respects, to bacteria. The giant virus (over tenfold larger than common viruses) is being examined as a possible link between viruses and "traditional" lifeforms (by way of bacteria).

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, and GPs often prescribe 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

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 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 PIE base *weis- "to melt away, to flow," used of foul or malodorous fluids, cognate to Sanskrit viṣam "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.