Prophylactic and therapeutic effects of human immunoglobulin on the pathobiology of HSV-1 infection, latency, and reactivation in mice.

Abstract

Pooled human immunoglobulin (IgG) was evaluated as prophylaxis and treatment of HSV-1 infection in mice. We compared the effects of IgG on the course of acute infection and spread of virus through the nervous system, as well as on the establishment, maintenance, and reactivation of virus from latency. Balb/c mice received a single 3.75 mg intraperitoneal injection of IgG 24 h before or 24 h, 48 h, or 72 h after ocular infection with 10(6) pfu of HSV-1 strain McKrae. Treatment with IgG protected against death in a time-dependent manner (P < 0.001 for -24 h vs. +48 h and +72 h IgG treatment groups). Viral shedding from the eyes was reduced more in mice treated with IgG at -24 h or +24 h relative to animals treated at +48 h. Viral titers in the eyes were reduced in mice treated with IgG at +24 h, but not at +48 h. In ganglia, virus recovery was reduced (P < 0.05) in mice treated at -24 h, +24 h, or +48 h relative to untreated mice, or ones treated at +72 h. In brains, similar results were observed in mice treated at -24 h, +24 h, or +48 h relative to +72 h. Upon explantation, virus reactivated from all ganglia of all surviving mice regardless of treatment group. DNA quantitation showed that mice pretreated with IgG tended towards lower quantities of latent genome copies compared to +24 h treatment and +48 h treatment. UV irradiation induced reactivation in vivo in 16/40 pretreated mice, 20/29 mice treated at +24 h, and in 8/8 mice treated at +48 h (P = 0.03 and P = 0.004, for comparisons at -24 h vs. +24 h, and -24 h vs. +48 h, respectively). Histopathological studies revealed that mice pretreated and treated with IgG had milder encephalitis and reduced virus spread compared to untreated mice. Pooled human IgG attenuates the spread of, and morbidity from, HSV-1 if given before and within 2 days after ocular infection.