Studies on dengue 2 virus infection in cyclophosphamide-treated rhesus monkeys

Dengue 2 virus (D2V) replication has been demonstrated in cultured primate mononuclear phagocytes, mitogen treated lymphocytes and lymphoblastoid cells. To determine which of these cell types might play an important role in sustaining infection in vivo, nine rhesus monkeys were immunosuppressed with cyclophosphamide and then infected with D2V. Maintenance doese which held total white blood cell counts to <3000/mm³ ablated both primary and secondary antibody responses. Six successfully immunosuppressed animals circulated virus and infected monocytes in blood for prolonged periods. Virus was recovered from lymphatic organs and visualized in tissue mononuclear leukocytes in two subjects dying during the experimental period. The results argue against the hypothesis that lymphoblasts play an important role in dengue virus infection but are consistent with the possibility that mononuclear phagocytes are the site of viral replication in vivo.This research was supported by a contract from the U.S. Army Medical Research and Development Command, DADA 17-73-C3083. We wish to thank Susan Cate, Jill Kelly and Patricia Iwamoto for excellent technical assistance