Mechanism of Innate Resistance to Flaviviral Encephalitis.
Annual rept. 1 Mar 75-31 Dec 76,
YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE
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Immunological factors that influence the phenotypic expression of genetic resistance or susceptibility to lethal flavivirus infection were investigated in 2 congenic strains of mice C3HRV resistant to lethal infection and C3HHe susceptible to lethal infection. Resistance was abrogated by immunosuppression with cyclophosphamide or rabbit antimouse thymocyte serum. Immunosuppressed mice had higher yields of virus from target tissues such as brain than non-immunosuppressed mice. Paradoxically, C3HHe mice given antithymocyte serum had an increased average survival time. Following immunization with inactivated virus and adjuvant both strains of mice withstood ip challenge with virus. In contrast only resistant mice C3HRV were unable to withstand ic challenge. Similarly C3HRV mice were able to withstand ic challenge after passive immunization with anti-Banzi immune ascitic fluid, whereas C3HHe mice succumbed. Attempts to protect susceptible mice from lethal infection by transfer of non-immune C3HRV splenic cells were generally unrewarding, although in several experiments recipients of non-immune resistant type cells had an increase in average survival time of several days. An in vitro microcytotoxicity test for Banzi virus was developed. It was shown that splenic cells from both resistant and susceptible mice were specifically cytotoxic for virus-infected L-929 target cells.
- Medicine and Medical Research