Cell surface expression of yellow fever virus non-structural glycoprotein NS1: consequences of interaction with antibody.
Among antibodies to flaviviral proteins only those directed at the virion envelope protein (E) or the non-structural 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-NS1, or E monospecific serum or monoclonal antibodies to bind to yellow fever virus (YFV)-infected cells and of anti-NS1 or E serum to sensitize them to CMC. Although both anti-NS1 and anti-E antibody bound to YFV-infected cells, CMC was observed only with anti-NS1 antibody. Greater binding by anti-NS1 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-NS1 monoclonal antibody or monospecific, anti-NS1 rabbit serum and complement. Taken together these results are consistent with the hypothesis that CMC subserved by anti-NS1 antibody provides an alternative to direct neutralization of virus in the protective immune response to flaviviral infection.
Schlesinger
J J
JJ
Department of Medicine, Rochester General Hospital, New York.
Brandriss
M W
MW
Putnak
J R
JR
Walsh
E E
EE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics*; D002213:Capsid / Q000032:analysis / Q000235:genetics*; D002462:Cell Membrane / Q000276:immunology; D002472:Cell Transformation, Viral; D003165:Complement System Proteins / Q000276:immunology; D007700:Kinetics; D014709:Vero Cells; D014758:Viral Core Proteins / Q000032:analysis / Q000235:genetics*; D017361:Viral Nonstructural Proteins; D015005:Yellow fever virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D003165:Complement System Proteins