LESSION—2

                     Viruses,   Viroids   and   Prions

                                         VIRUSES

        The name virus (Latin virus=venom of poisonous fluid) was given by Pasteur to the causative agents of infectious diseases. Adolph Mayer (1885), a Dutch scientist, and D. J. Ivanowsky (1892), a Russian scientist, recognized certain microbes as causative agent of mosaic disease of tobacco. The basic criterion used to differentiate these agents from other familiar microbial agents of diseases was their ability to pass through bacteria-proof filters. These agents were thus designated as filterable viruses (now it has been established that many microbes of bacterial nature are also capable of passing through such filters, therefore, the word filterable was subsequently dropped).

               M.  W.  Beijerinck, a Dutch bacteriologist, demonstrated in 1898 that viruses differ from other cellular organisms. He discovered that the virus of tobacco mosaic disease could be precipitated from a suspension of alcohol without losing its infectious power and the fluid was capable of diffusing through agar gel. These characteristics are not possessed by bacteria or any other living organism. This led Beijerinck to believe that the fluid itself was living and he put forward the principle of Contagium vivum fluidum (infectious living fluid). In the same year, Loeffer and Frosch demonstrated that foot and mouth disease of cattle is caused by a filtrate apparently free of any bacteria. They concluded that if the agent of this disease is particulate, it must be smaller than the diameter of the smallest known bacteria. Nearly 40 years after these observations, the structure of virus was studied by Wendell M.  Stanley, an organic chemist, in 1935. He showed that the infectious principle of virus could be crystallized and that the crystals consisted largely of proteins. For many years it was thought that virus is simply a protein molecule, but later it was discovered that virus contains a small but constant amount of RNA or DNA in addition to protein. A virus is therefore, not simply a protein but a nucleoprotein and its infectious principle is the nucleic acid rather than protein. Stanley was awarded Nobel prize in 1946 for this discovery.

          Subsequently, many already known diseases like mumps chicken pox and hog cholera, as well as many newly identified diseases, were found to be caused by filterable agents, i.e., viruses. An English scientist, F.W. Twort (1915), and a Canadian, Felix d, herelle (1917), independently discovered that a virus was capable of dissolving or lysing bacterial cells. This virus was designated as bacteriophage, i.e., eater of bacteria.

        Luria (1953) described viruses as submicroscopic entities capable of being introduced into specific living cells and reproducing inside such cells only. According to Andre Lwoff (1966), a Nobel Laureate French virologist, the most appropriate definition of viruses is viruses are viruses. Some biologists think that viruses are descendants of cellular organisms that have become highly specialized as parasites, others consider that viruses were originally fragments of DNA or RNA broken off from the nucleic acid of cellular organisms. However, it is now well established that viruses are obligately  parasitic, self replicating non-cellular organism and essentially composed of a protein covering surrounding a central nucleic acid molecule (either DNA or RNA). Most of the modern virologists prefer not to define viruses by any specific definition but describe them by their various physical, chemical, biological and clinical properties.

                                                  Origin  of  Viruses                            

       The origin of viruses has been a subject of considerable speculation in the scientific                  community. However there is general agreement that viruses (phage) probably infected            bacteria during the period when Archaea and Eubacteria were the sole life forms on the            earth. Later, when eukaryotes evolved they were also attacked by viruses. Following                 three major theories have been proposed for the origin of viruses.

[                          [I]  Theory  of  Coevolution

       According to this theory viruses originated in the primordial soup and coevolved with the more complex life forms (e.g., Archaea and Eubacteria). The earliest self replicating genetic system was probably composed of RNA. RNA can promote RNA polymerization and this process was probably accelerated by the proteins present in the primordial soup. The DNA template is much more effective and originated early in evolution. RNA then became the messenger between the DNA template and protein synthesis. Thus the genetic code came into being and permitted orderly replication. Gradually the early replicative forms became complex and became encased in a lipid sac; thus it metabolic machinery became separated from the surrounding environment. Such individual units may have been the ancestor of the Archaea and Eubacteria. At the same time some replicative forms, composed mainly of self-replicative nucleic acid surrounded by protein coat, may have retained simplicity. This entity was the forerunner of the virus. It gradually evolved acquired the ability to invade and take over the genetic machinery of a host. Thus there was coevolution of the bacterium and virus.