Comparative studies on the neurovirulence of temperature-sensitive and temperature-resistant viruses of enterovirus 71 in monkeys.

The neurovirulence of strain BrCr of enterovirus 71 (E71) was compared in monkeys between temperature-sensitive (ts) and temperature-resistant (tr) viruses. Comparisons are made relative to clinical disease, pathologic findings, serum neutralizing antibody titers, CNS virus replication as measured by infectivity titrations and immunofluorescence. Clinically, ts virus did not produce a clinical disease. The tr virus, however, produced paralysis. Pathologically, little or no nerve cell damage was found in the CNS of monkeys inoculated with ts virus, although mild to moderate interstitial changes occurred. In monkeys inoculated with tr virus, marked nerve cell damage and inflammatory reaction were found in the CNS. Serum neutralizing antibody titers in monkeys inoculated with ts virus rose on day 25. No virus was detected in the CNS of monkeys inoculated with ts virus, while a high virus titer was detected in the CNS of monkeys inoculated with tr virus. No specific immunofluorescence was detected in the nerve cells of the CNS in monkeys inoculated with ts virus, but specific fluorescence was detected in the nerve cells of the CNS in monkeys inoculated with tr virus. Virus growth in the CNS correlated well with the severity of clinical and pathologic findings, and immunofluorescent studies. The results show that ts virus was much less neurovirulent than tr virus, indicating that ts virus resembles the attenuated poliovirus which could not grow at a higher temperature. It is inferred that the genetic factors which influence the reproductive capacity of E71 at a higher temperature are very closely correlated with the neurovirulence.