Neutralization of Epstein-Barr Virus by Nonimmune Human Serum: ROLE OF CROSS-REACTING ANTIBODY TO HERPES SIMPLEX VIRUS AND COMPLEMENT

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Abstract

These studies were carried out to investigate the mechanism of neutralization of purified Epstein-Barr virus (EBV) by fresh human serum from normal individuals lacking antibody to the EBV viral capsid (VCA) and nuclear antigens (EBNA). Such individuals thus lack serological evidence of immunity to EBV. Although an enzyme-linked immunosorbent assay (ELISA) with highly purified immobilized EBV detected low levels of IgG antibody reactive with EBV in these normal nonimmune sera, this antibody failed to neutralize EBV in the absence of complement. Studies with depleted sera and mixtures of purified complement proteins at physiologic concentrations showed that the IgG antibody and C1, C4, C2, and C3 of the classical pathway were able to fully neutralize EBV. Mixtures of the purified components of the alternative pathway at physiologic concentrations failed to neutralize purified EBV in the presence or absence of the antibody and the alternative pathway did not potentiate classical pathway-mediated neutralization. No evidence for a requirement for C8 was obtained, precluding lysis as the mechanism of neutralization. Since C3 deposition on the viral surface accompanied classical pathway activation, viral neutralization is most likely secondary to the accumulation of complement protein on the viral surface. A coating of protein on the virus could interfere with attachment to, or penetration of potentially susceptible cells.

Authors

Glen R. Nemerow, Fred C. Jensen, Neil R. Cooper