Protection of newborn mice from a lethal herpes simplex virus infection by human interferon, antibody, and leukocytes.

Newborn mice infected i.p. with a lethal dose of herpes simplex virus (HSV) were protected by a combination of human interferon and human mononuclear cells (MC) when it was administered i.p. one day before infection (35.2% survived, p < 0.001). The HSV immune status of the MC donors did not affect this protection. The number of MC required in the presence of 100 units of interferon was 5 × 106 to 5 × 105/mouse. The dose of interferon required in the presence of 5 × 106 MC was 100 to 10 U. Highest survival was achieved with 5 × 106 MC and 100 U of interferon. The active human effector cell in this system was either a lymphocyte or a monocyte-macrophage but not a polymorphonuclear leukocyte. Treatment of mice with interferon and MC after viral inoculation was not successful. Protection by human WISH cells (a nonleukocyte) and interferon was demonstrated (55% survival, p < 0.001 ), which suggested that protection was due to interferon induced cross-species active antiviral protein production. The human interferon stimulated human but not murine or WISH cell natural killer cytotoxicity (NKC) in vitro. Mice receiving human interferon, MC, and subneutralizing doses of anti-HSV antibody before HSV infection were almost completely (95.2%) protected, and were protected significantly better (p < 0.001) than mice receiving either MC plus interferon or MC plus antibody. Although adult MC could mediate this protection, all mice receiving MC from neonatal humans plus antibody and interferon died (p < 0.001). In vitro experiments showed that protection was not due to viral neutralization. This is the first evidence for either in vivo human antiviral NKC or cross-species antiviral protein protection as well as defective in vivo human neonatal MC function in this system.