Protective anti-reovirus monoclonal antibodies and their effects on viral pathogenesis.
We used a recently isolated and characterized panel of monoclonal antibodies (MAbs) specific for cross-reactive determinants on reovirus outer capsid proteins to define mechanisms of antibody-mediated protection 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 following. (i) MAbs specific for each of the viral outer capsid proteins (sigma 1, sigma 3, and mu 1) and the core spike protein (lambda 2) were protective under certain circumstances. (ii) In vitro properties of MAbs, 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 did not act at a single stage during pathogenesis to mediate protection; instead, protective MAbs were capable of altering a variety of stages in reovirus pathogenesis. (iv) MAbs protective against one reovirus also protected against other reoviruses that utilized different pathogenetic strategies, suggesting that the viral epitope bound by an antibody rather than the pathogenetic strategy employed by the virus is a critical determinant of antibody-mediated protection in vivo. (v) A prominent mechanism of protective MAb action is inhibition of viral spread through nerves from a site of primary replication (e.g., the intestine or muscle tissue) to the central nervous system.
Department of Neurology, University of Colorado Health Sciences Center, Denver.
K L
KL
Tyler
M A
MA
Mann
B N
BN
Fields
H W
HW
Virgin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity; D002213:Capsid / Q000276:immunology*; D014644:Genetic Variation; D007116:Immunization, Passive; D007739:L Cells; D012089:Mammalian orthoreovirus 3 / Q000276:immunology; D051379:Mice; D012088:Reoviridae Infections / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral