Virus

I

Introduction

Virus (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 (see Diseases of Animals).

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.

II

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.

III

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.

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.

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.

IV

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.