Intranasal Infection of Monkeys with Japanese Encephalitis Virus: Clinical Response and Treatment with a Nuclease-Resistant Derivative of Poly(I)-Poly(C).

摘要

In the first experiment 2 rhesus (Macaca mulatta) and 2 cynomolgus (Macaca fasicularis) monkeys were innoculated intranasally (i.n.) with 30,000,000 plaque-forming units (PFU) of the Peking strain Japanese encephalitis virus (JEV) to establish the time course of infection and resulting mortality. The onset of clinical signs for both species of monkeys occurred on days 5 to 9, with fever of several days duration, anorexia and depression. Death ensued in 11 to 12 days. An i.n. median lethal dose equivalent to 25000 PFU of the Peking strain of JEV was determined in 16 additional cynomolgus monkeys. Clinical signs of infection, virus-neutralizing antibody formation, and mortality were dose-dependent for the doses of virus inoculated. A nuclease-resistant complex of polyriboinosinic.polyribocyticylic acid, poly-l-lysine and carboxmethylcellulose (poly(ICLC)) reduced mortality by 50% in monkeys treated initially 8 or 24 hours after virus challenge.