Interferon induction and sensitivity as correlates to virulence of Venezuelan encephalitis viruses for hamsters

Venezuelan encephalitis (VEE) virus strains, which differ in virulence for adult hamsters, were compared with respect to (a) sensitivity to hamster interferon (IF) in vitro and in vivo and (b) induction of IF in plasma and target tissues (spleen, bone marrow and brain) following subcutaneous inoculation. In vitro, in cultures of a continuous line of hamster kidney cells, hamster interferon inhibited the replication of a benign VEE strain (BeAr 35,645) more than another benign strain (TC-83 vaccine) or two hamster-virulent strains (68 U 201 and Trinidad donkey). In vivo, in hamsters given poly I: poly C 24 hours before virus to induce interferon formation, BeAr 35,645 and TC-83 virus infections were prevented more frequently than infections with virulent strains Trinidad donkey and 68U201. Benign VEE strains BeAr 35,645 and TC-83 induced only slightly lower concentrations of IF in plasma, bone marrow, spleen and brain than virulent strains Trinidad donkey, 63Z21 and 68U201. However, concentrations of infectious BeAr 35,645 virus were significantly lower in these tissues than virulent strains, resulting in higher ratios of IF: invectious virus, suggesting efficient interferon induction. Benign strain TC-83 showed irregular relationships between IF and infectious virus in plasma or blood and tissues, Splenectomy significantly depressed plasma plasma IF responses to TC-83 virus 20 to 30 hours after inoculation. Interferon appears to be a factor that influences virulence of VEE viruses for hamsters.