Virus..

VIRUS

Virus (biology) (Latin, “poison”), any of a number of organic entities consisting simply of genetic material surrounded by a protective coat. The term “virus” was first used in the 1890s to describe agents that caused diseases but were smaller than bacteria. By itself a virus is a lifeless form, but within living cells it can replicate many times and harm its host in the process. There are at least 3,600 types of virus, hundreds of which are known to cause a wide range of diseases in humans, other animals, insects, bacteria, and plants.

The existence of viruses was established in 1892, when Russian scientist Dmitry I. Ivanovsky discovered microscopic particles later known as the tobacco mosaic virus. The name virus was applied to these infectious particles in 1898 by the Dutch botanist Martinus W. Beijerinck. A few years later, viruses were found growing in bacteria; these viruses were dubbed bacteriophages. Then, in 1935, the American biochemist Wendell Meredith Stanley crystallized tobacco mosaic virus and showed that it is composed only of the genetic material called ribonucleic acid (RNA) and a protein covering. In the 1940s development of the electron microscope made visualization of viruses possible for the first time. This was followed by development of high-speed centrifuges used to concentrate and purify viruses. The study of animal viruses reached a major turning point in the 1950s with the development of methods to culture cells that could support virus replication in test tubes. Numerous viruses were subsequently discovered, and in the 1960s and 1970s most were analysed to determine their physical and chemical characteristics.

Characteristics

Viruses are submicroscopic intracellular parasites that consist of either RNA or deoxyribonucleic acid (DNA)—never both—plus a protective coat of protein or of protein combined with lipid or carbohydrate components. The nucleic acid is usually a single molecule, either singly or doubly stranded. Some viruses, however, may have nucleic acid that is segmented into two or more pieces. The protein shell is termed the capsid, and the protein subunits of the capsid are called capsomeres. Together these form the nucleocapsid. Other viruses have an additional envelope that is usually acquired as the nucleocapsid buds from the host cell. The complete virus particle is called the virion. Viruses are obligate intracellular parasites; that is, their replication can take place only in actively metabolizing cells. Outside living cells, viruses exist as inert macromolecules (very large molecules).

Viruses vary considerably in size and shape. Three basic structural groups exist: isometric; rod shaped or elongated; and tadpole-like, with head and tail (as in some bacteriophages). The smallest viruses are icosahedrons (20-sided polygons) that measure about 18 to 20 nanometres wide (one-millionth of a millimetre = 1 nanometre). The largest viruses are rod shaped. Some rod-shaped viruses may measure several microns in length, but they are still usually less than 100 nanometres in width. Thus, the widths of even the largest viruses are below the limits of resolution of the light microscope, which is used to study bacteria and other large micro-organisms.

Many of the viruses with helical internal structure have outer coverings (also known as envelopes) composed of lipoprotein or glycoprotein, or both. These viruses appear roughly spherical or in various other shapes, and they range from about 60 to more than 300 nanometres in diameter. Complex viruses, such as some bacteriophages, have heads and a tubular tail, which attaches to host bacteria. The pox viruses are brick shaped and have a complex protein composition. Complex and pox viruses are exceptions, however; most viruses have a simple shape.

Replication

Viruses do not contain the enzymes and metabolic precursors necessary for self-replication. They have to get these from the host cells that they infect. Viral replication, therefore, is a process of separate synthesis of viral components and assembly of these into new virus particles. Replication begins when a virus enters the cell. The virus coat is removed by cellular enzymes, and the virus RNA or DNA comes into contact with ribosomes (cell organs that synthesize proteins) inside the cell. There the virus RNA or DNA directs the synthesis of proteins specified by the viral nucleic acid. The nucleic acid replicates itself, and the protein subunits constituting the viral coat are synthesized. Thereafter, the two components are assembled into a new virus. One infecting virus can give rise to thousands of progeny viruses. Some viruses are released by destruction of the infected cell. Others are released by budding through cell membranes and do not kill the cell. In some instances, infections are “silent”—that is, viruses may replicate within the cell but cause no obvious cell damage.

Lytic and Lysogenic Cycles of a Bacteriophage. All bacteriophages (viruses that parasitize bacteria) have a lytic or infectious cycle, in which the virus, incapable of replicating itself, injects its genetic material into a bacterium. By pirating its host’s enzymes and protein-building capacities, the virus can reproduce and repackage, making about 100 new copies before it bursts from and destroys the bacterium. Some bacteriophages, however, behave differently when they infect a bacterium. The injected genetic material instead integrates itself into its host DNA, passively replicating with it to be inherited by bacterial daughter cells. In about 1 in 100,000 of these lysogenic cells, the viral DNA spontaneously activates and starts a new lytic cycle.

The RNA-containing viruses are unique among replicative systems in that the RNA can replicate itself independently of DNA. In some cases, the RNA can function as messenger RNA (see Genetics), indirectly replicating itself using the cell's ribosomal and metabolic precursor systems. In other cases, RNA viruses carry within the coat an RNA-dependent enzyme that directs the synthesis of virus RNA. Some RNA viruses, which have come to be known as retroviruses, may produce an enzyme that can synthesize DNA from the RNA molecule. The DNA thus formed then acts as the viral genetic material.

Viral Replication Outside of a host cell, a virus is an inert particle. Once inside a cell, a virus can replicate many times, creating thousands of viruses that leave the cell to find host cells of their own. Viruses that cause disease do so by destroying or damaging cells as they leave them.

Bacterial viruses and animal viruses differ somewhat in their interaction with the cell surface during infection. The “T even” bacteriophage that infects the bacterium Escherichia coli, for instance, first attaches to the surface and injects its DNA directly into the bacterium. No absorption and uncoating take place. The basic events of virus replication, however, are the same after the nucleic acid enters the cell.

Viruses in Medicine

Viruses represent a major challenge to medical science in combating infectious diseases. Many cause diseases that are of major importance to humans and that are extraordinary in their diversity.

Included among viral diseases is the common cold, which affects millions of people every year. Recent research has even indicated that the AD-36 virus, which causes cold-like symptoms, affects food-energy absorption and more than doubles the normal layer of body fat in animals. About 30 per cent of obese people had contracted AD-36 compared with 5 per cent of lean people, and so this virus may contribute to obesity in a percentage of people. Other viral diseases are important because they are frequently fatal. These diseases include rabies, haemorrhagic fevers, encephalitis, poliomyelitis, and yellow fever. Most viruses, however, cause diseases that usually only create acute discomfort unless the patient develops serious complications from the virus or from a bacterial infection. Some of these diseases are influenza, measles, mumps, cold sores (also known as herpes simplex), chickenpox, shingles (also known as herpes zoster), respiratory diseases, acute diarrhoea, warts, and hepatitis. Still others, such as rubella (also known as German measles) virus and cytomegalovirus, may cause serious abnormalities or death in unborn infants. Acquired immune deficiency syndrome (AIDS) is caused by a retrovirus. Only two retroviruses are unequivocally linked with human cancers (see Leukaemia and HTLV), but some papilloma virus forms are suspected. Increasing evidence also indicates that other viruses may be involved in some types of cancer and in chronic diseases such as multiple sclerosis and other degenerative diseases. Some of the viruses take a long time to cause disease; kuru and Creutzfeldt-Jakob disease, both of which gradually destroy the brain, are slow virus diseases.

Viruses that cause important human disease are still being discovered. Most can be isolated and identified by laboratory methods, but these usually take several days to complete. One of the most recently discovered viruses is rotavirus, the causal agent of infant gastroenteritis.

Spread

To cause new cases of disease, viruses must be spread from person to person. Many viruses, such as those causing influenza and measles, are transmitted by the respiratory route when virus-containing droplets are put into the air by people coughing and sneezing. Other viruses, such as those that cause diarrhoea, are spread by the faecal-oral route. Still others, such as yellow fever and viruses called arboviruses, are spread by biting insects. Viral diseases are either endemic (present most of the time), causing disease in susceptible people, or epidemic—that is, they come in large waves and attack thousands of people. An example of an epidemic viral disease is the worldwide occurrence of influenza almost every year.

Treatment

Smallpox Vaccination This drawing shows a doctor administering the smallpox vaccine, first discovered in 1796 by British physician Edward Jenner. Jenner found that infecting a patient with cowpox, a minor disease, produced immunity to smallpox, which can cause disfigurement or death. His discoveries won him worldwide renown.

Currently, no completely satisfactory treatments exist for viral infections, because most drugs that destroy viruses also damage the cell. The drug amantadine is used extensively in some countries for treatment of respiratory infections caused by influenza-A viruses, and the drug AZT is used in the treatment of HIV.

One promising antiviral agent, interferon, is produced by the cell itself. This non-toxic protein, which is produced by some animal cells infected with viruses, can protect other cells against such infection. The use of interferon for treating cancer is under intensive study. Until recently, study of the use of interferon has been restricted by its limited availability in pure form. However, new techniques of molecular cloning of genetic material (see Genetic Engineering) now make it possible for scientists to obtain the protein in larger quantities. Its relative value as an antiviral agent has already been established.
The only effective way to prevent viral infection is by the use of vaccines. For example, vaccination for smallpox on a worldwide scale in the 1970s eradicated this disease. Many antiviral vaccines have been developed for humans and other animals. Those for humans include vaccines for rubeola (also known as measles), rubella, poliomyelitis, and influenza. Immunization with a virus vaccine stimulates the body's immune mechanism to produce a protein—called an antibody—that will protect against infection with the immunizing virus. The viruses are always altered before they are used for immunization so that they cannot themselves produce disease.

Plant Diseases

Viruses cause a wide variety of diseases in plants and frequently cause serious damage to crops. Common plant-disease viruses are turnip yellow mosaic virus, potato leaf roll virus, and tobacco mosaic virus. Plants have rigid cell walls that plant viruses cannot penetrate, so the most important means of plant-virus spread is provided by animals that feed on plants. Often, healthy plants are infected by insects that carry on their mouthparts viruses acquired while feeding on other infected plants. Nematodes (also known as roundworms) may also transmit viruses while feeding on the roots of healthy plants.

Plant viruses can accumulate in enormous quantities within infected cells. For instance, tobacco mosaic virus may represent as much as 10 per cent of the dry weight of infected plants. Studies on the interaction of plant viruses with plant cells are limited, because plants often cannot be infected directly, but only by means such as an insect vector. Cell cultures in test tubes, which can be infected with plant viruses, are not generally available.

Role in Research

The study of viruses and their interaction with host cells has been a major motivation for the host of fundamental biological studies at a molecular level. For example, the existence of messenger RNA, which carries the genetic code from DNA to define what proteins are made by a cell, was discovered during studies of bacteriophages replicating in bacteria. Studies of bacteriophages have also been instrumental in delineating the biochemical factors that start and stop the utilization of genetic information. Knowledge of how virus replication is controlled is fundamental to understanding biochemical events in higher organisms.

The reason that viruses are so useful as model systems for studying events that control genetic information is that viruses are, in essence, small pieces of genetic information that is different from the genetic information of the cell. This allows scientists to study a smaller and simpler replicating system, but one that works on the same principle as that of the host cell. Much of the research on viruses is aimed at understanding their replicative mechanism in order to find ways to control their growth, so that viral diseases can be eliminated. Studies on viral diseases have also contributed greatly to understanding the body's immune response to infectious agents. Antibodies in blood serum, as well as secretions of the mucous membranes, all of which help the body eliminate foreign elements such as viruses, have been more thoroughly characterized by studying their responses to viral infection. Intense scientific interest is now concentrated on studies designed to isolate certain viral genes. These genes can be used in molecular-cloning systems to produce large amounts of particular virus proteins, which can in turn be used as vaccines.