PROTECTIVE ANTI-REOVIRUS MONOCLONAL-ANTIBODIES AND THEIR EFFECTS ON VIRAL PATHOGENESIS

We used a recently isolated and characterized panel of monoclonal anti bodies (MAbs) specific for cross-reactive determinants on reovirus out er capsid proteins to define mechanisms of antibody-mediated protectio n in vivo. We studied the capacities of MAbs to protect against lethal infection with reoviruses which differ in site of primary replication , route of spread, and central nervous system tropism. We found the fo llowing. (i) MAbs specific for each of the viral outer capsid proteins (sigma1, sigma3, and mu1) and the core spike protein (lambda2) were p rotective under certain circumstances. (ii) In vitro properties of MAb s, including isotype, neutralization of viral infectivity, inhibition of virus-induced hemagglutination, and avidity of binding, were poorly predictive of the capacities of MAbs to protect in vivo. (iii) MAbs d id not act at a single stage during pathogenesis to mediate protection ; instead, protective MAbs were capable of altering a variety of stage s in reovirus pathogenesis. (iv) MAbs protective against one reovirus also protected against other reoviruses that utilized different pathog enetic strategies, suggesting that the viral epitope bound by an antib ody rather than the pathogenetic strategy employed by the virus is a c ritical determinant of antibody-mediated protection in vivo. (v) A pro minent mechanism of protective MAb action is inhibition of viral sprea d through nerves from a site of primary replication (e.g., the intesti ne or muscle tissue) to the central nervous system.