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

That the hemagglutinin (HA) of reovirus, encoded in the SI gene, determines the cen-tral nervous system (eNS) cell tropism of reovirus types I and 3 was shown using recom-binant clones containing nine genes from one serotype and the SI gene from the other. Clone I.HA3 contains nine genes from type I and the SI gene from type 3; 3.HAI is the reciprocal clone. Type 3 and I.HA3 cause a fatal encephalitis in newborn mice with neuronal destruction but no ependymal cell damage, whereas type I and 3.HAI 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 I.HA3 or in neuronal cells of mice infected with type I or 3.HAI. With type 3 or clones containing <the type 3 HA, maximal brain titers were 1010 plaque-forming units; maximal titers were 108 plaque-forming units for type I or clones containing the type I HA. This pattern of reovirus virulence for CNS probably relates to the specific interaction of viral HA with neuronal or ependymal surface receptors. Reovirus types 1 and 3 exhibit differing tropism for cells in the central nervous system (CNS) and, as a consequence of their differing tropisms, pro-duce distinct patterns of virulence. Specifically, when reovirus type 3 is inoculated intracerebrally (ic) into newborn mice, an acute encephalitis de-velops that is uniformly fatal and is accompanied by destruction of neuronal cells without damage to ependymal cells [1], whereas ic inoculation of reovirus type 1 produces a nonfatal infection of the ependymal cells that line the ventricular cavities of the brain, with little or no effect on neurons. Hydrocephalus often develops as a se-quel to the ependymal damage [2]. Reoviruses are animal viruses whose genomes consist of 10 segments of double-stranded RNA (dsRNA) classified according to size: three large Received for publication November 5, 1979, and in revise