Molecular basis of reovirus neurovirulence: role of the M2 gene in avirulence.

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Abstract
A number of field isolates of reovirus 3 were examined to determine their relative neurovirulence after intracerebral inoculation. One isolate had decreased neurovirulence. This avirulent strain showed the typical type 3 neural tropism but grew significantly less well in brain tissue than T3 (Dearing) and the other type 3 reoviruses. The avirulent virus was not temperature-sensitive, and its yield in mouse L cells in vitro was similar to that of the laboratory strains. To determine the reason that this clone was avirulent, a series of reassortant progeny clones was isolated from crosses between the avirulent strain and T1 (Lang) and T3 (Dearing). Using these reassortants, avirulence shown to be a property of the M2 gene segment. The M2 segment was also responsible for conferring greater sensitivity to chymotryptic digestion on the avirulent strain, compared to more virulent strains. Prior studies determined that the localization of virus in different cell types in the brain (tropism) is a property of the viral hemagglutinin, the products of the S1 RNA genome segment. However, the basis for relative neurovirulence does not reside in the viral hemagglutinin, and the nature of neurovirulence is thus clearly multigenic.