1. What is a virus: A very small organism, which can grow and multiply, only inside of a cell. It requires the content of the cell to manufacture the various components of the virus. These components are; i) DNA or RNA nucleic acids. These are the genes of the virus. Viral particles contain either RNA or DNA but not both, whereas bacteria and cells have both RNA and DNA. The amount of DNA or RNA in a virus varies depending on the type of virus. Small viruses, e.g. papillomavirus have about 9,000 nucleotide molecules strung in a row. Big viruses, e.g. a herpesvirus can have 150,000 nucleotides. ii) A protein (or proteins) which associate with the DNA or RNA and provides some protection as the virus passes between cells. The proteins make up the capsid of the virus. iii) Some viruses also have an outer protective layer of proteins in lipid envelope, and sometimes also between the capsid and the envelope (termed tegument proteins).

2. Viruses are classified in several ways, for example. i) Whether the viral particles contain RNA or DNA. Some RNA viruses convert to DNA after they enter a cell and are called retroviruses. ii) Whether the genome is single (ss) or double stranded (ds). iii) For single stranded RNA viruses, the sequence may directly code for its protein (positive, +ve, stranded), or consist of the opposite or negative, -ve, strand. iv) The genome may be linear or circular and may be in a single segment, or in multiple segments. iv) The genome size and overall shape of the virus and whether an envelope is present are also major criteria used for classification. v) Finally, the kinds of diseases produced can distinguish different viruses. Related viruses are successively grouped into species, genera, families and orders (see Table).

3. Viruses which can cause disease are termed pathogenic. Examples of virus induced diseases include; influenza, the common cold, chickenpox, measles, mumps, rubella, hepatitis, infectious mononucleosis, polio, etc. Some viruses are thought to cause cancer. A retrovirus called human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS).

4. Some viruses can directly damage cells by usurping the cells metabolic resources and/or by producing toxic components which interfere with the cells' normal functions. These viruses will generally induce a cytopathic effect (CPE) in tissue culture cells. Viruses can also cause cells to express viral and/or altered cellular components which become targets for anti-cellular immunity. Finally, HIV directly attacks the immune system leaving the infected host vulnerable to secondary infections by other pathogens.

5. Certain types of cellular proteins have the peculiar property that when in an abnormal configuration, they will induce the corresponding normal protein to assume the same abnormal configuration. These set up a chain reaction leading to the progressive accumulation of abnormally configured proteins. Such proteins have been termed "prions" for "proteinaceous infectious particles". Certain humans and animals inherit genetically altered normal protein with an enhanced tendency to "spontaneously" generate the small quantity of the abnormally configured protein to begin the process. If other individuals become exposed to these proteins, e.g. by ingestion with food, disease can occur along with the potential of further transmission.

Prion diseases include scrapie in sheep, bovine spongiform encephalopathy or mad cow disease in cows and both Creutzfeldt-Jakob disease and kuru in humans.

An assay based on the detection of a neuronal protein 14-3-3 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease was recently described by Dr. Micael Harrington and his colleagues.

LABORATORY DIAGNOSIS OF VIRAL INFECTIONS

Serological, molecular biological and tissue culture methods are used to diagnose viral infections and to accertain the extent of viral damage and the quality and intensity of the body's immune response.

The antibody response to a viral infection normally starts with the relatively transient production of IgM followed by a long lasting production of IgG. For this reason, a specific IgM antibody response can generally be taken as a sign of early infection. The serological detection of free viral antigen can precede the earliest serological response and this type of assay can be useful for certain infections, e.g. parvovirus B19, HIV, hepatitis B virus (HBV) and human herpesvirus-6 (HHV-6). Antigen assays can also be used to distinguish persisting infection, in spite of IgG response, from a cured infection. Again, this type of approach has been employed with HIV and HHV-6.

The quality and intensity of the anti-viral cellular immune responses can be assessed using lymphocyte subset analyses, natural killer cell mediated cytotoxicity, and measurements of cytokine production including IL2, IL4, interferon, etc.

For some infections, actual culture of the virus can provide conclusive evidence of active infection, as well as the isolate for susceptibility studies. Active infection can also be inferred from the results of molecular probe based assays, including the use of polymerase chain reaction and branched DNA procedures.

Individuals can harbor multiple viral infections which may potentiate each other and lead to atypical manifestations.

The extent of organ damage can be assessed directly using tissue biopsies, or measured indirectly by assaying for various components released from the infected organ. For example 14-3-3 protein in Creutzfeldt-Jakob disease.

Finally, sequential measurements can provide a means to determine natural outcome as well as response to specific intervention.