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Among antibodies to flaviviral proteins only those directed at the virion envelope protein (E) or the nonstructural glycoprotein NS1 are known to confer protection. To investigate the possible role of complement-mediated cytolysis (CMC) in protection we measured the capacity of anti-NSl, or E monospecific serum or monoclonal antibodies to bind to yellow fever virus (YFV)-infected cells and of anti-NSl or E serum to sensitize them to CMC. Although both anti-NSl and anti-E antibody bound to YFV-infected cells, CMC was observed only with anti-NSl antibody. Greater binding by anti-NS 1 antibody suggested the presence of larger amounts of NS1 than E associated with the cell membrane. Using the cell membrane-impermeable, cross-linking reagent BS3, cell surface NS1, but not E, was detected as a homopolymer, a form in which bound antibody might be expected to activate complement more efficiently. Peak titres of progeny virus were reduced 10- to 100-fold when infected cells were treated with complement-fixing, anti-NSl monoclonal antibody or monospecific, anti-NSl rabbit serum and complement. Taken together these results are consistent with the hypothesis that CMC subserved by anti- NSl antibody provides an alternative to direct neutralization of virus in the protective immune response to flaviviral infection.
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