The genetic basis of viral virulence

Abstract

The precise genetic and molecular determ inants of viral virulence are poorly understood. Genetic studies with influenza and reovirus have indicated that virulence is multigenic. The high frequency of m utation of RNA viruses can complicate genetic analyses of virulence, resulting in phenotypes that are difficult to interpret. The ease with which the reoviruses reassort genome segments has made it possible to isolate reassortants from parental viruses causing different patterns of anim al disease. It has thus been feasible to show that each of the three outer capsid proteins plays a m ajor role in the pathogenesis of anim al infection: the viral haem agglutinin determines the specificity of the im mune response and cell and tissue tropism ; the p ic protein plays a central role in determ ining yield at portals of entry as well as in differentiated tissues; the δ3 protein inhibits host m acrom olecular synthesis. Thus virulence is clearly multigenic, with each of the viral components playing distinct roles.