Absolute linkage of virulence and central nervous system cell tropism of reoviruses to viral hemagglutinin.

That the hemagglutinin (HA) of reovirus, encoded in the S1 gene, determines the central nervous system (CNS) cell tropism of reovirus type 1 and 3 was shown using recombinant clones containing nine genes from one serotype and the S1 gene from the other. Clone 1.HA3 contains nine genes from type 1 and the S1 gene from type 3; 3.HA1 is the reciprocal clone. Type 3 and 1.HA3 cause a fatal encephalitis in newborn mice with neuronal destruction but no ependymal cell damage, whereas type 1 and 3.HA1 cause a nonfatal ependymal infection but no neuronal damage. Immunofluorescent studies showed no viral antigen in ependymal cells of mice infected with type 3 or 1.HA3 or in neuronal cells of mice infected with type 1 or 3.HA1. With type 3 or clones containing the type 3 HA, maximal brain titers were 10(10) plaque-forming units; maximal titers were 10(8) plaque-forming units for type 1 or clones containing the type 1 HA. This pattern of reovirus virulence for CNS probably relates to the specific interaction of viral HA with neuronal or ependymal surface receptors.