TREATMENT OF INTRACRANIAL ALPHAVIRUS INFECTIONS IN MICE BY A COMBINATION OF SPECIFIC ANTIBODIES AND AN INTERFERON INDUCER

Finding an effective treatment for viral infections that cause encepha litis remains an important problem. A model of human alphavirus infect ions, Semliki Forest virus, causes lethal encephalitis in weanling mic e. Mice are viremic within 24 hr of an intraperitoneal challenge with the equivalent of three 75% lethal doses of Semliki Forest virus. Viru s reaches the brain by 48 hr, and mortality results in all mice in 5-7 days. Introduction of virus intracranially accelerates the course of the infection. Neither anti-Semliki Forest virus hyperimmune serum nor the potent interferon inducer poly I:CLC given intraperitoneally are protective when used therapeutically after an intracranial virus infec tion, but a combination of 1,000 U hyperimmune serum and 80 mu g/mouse of poly I:CLC results in a 50% survival rate. This combination treatm ent of intracranial Semliki Forest virus infection eliminates detectab le viremia and reduces virus load in the brain over the course of the infection. These data show that when combined, specific antibody and a n interferon inducer can interact synergistically to protect mice from alphavirus infections of the central nervous system even when given a fter the virus is replicating in the target organ.