Replication of Dengue Viruses in Cultures of Peripheral Blood Leukocytes from Dengue-Immune Rhesus Monkeys

Abstract

Dengue virus of types 1, 2, and 4 replicated reproducibly in cultures of peripheral blood leukocytes from 18 dengue-immune rhesus monkeys but failed to multiple in peripheral blood leukocytes from 25 nonimmune monkeys. Replication was observed at input multiplicity of infection of 0.1 and 0.01 but irregularly at less than or equal to 0.001. Dengue viruses in permissive leukocytes achieved maximal titers on days 2-4 of culture. Viral replication in peripheral blood leukocytes from animals immune to a different type of dengue virus and in animals immune to two or more types of dengue virus was quantitatively similar to that in peripheral blood leukocytes from homotypically immune donors. Dengue virus permissiveness developed between two and three weeks after primary dengue infections. Leukocytes of animals that developed immunity to dengue virus remained permissive to in vitro infection by dengue virus of types 1 and 2 for prolonged periods, but within six months permissiveness to type 4 decreased. Thus an immunological dependence of in vitro dengue virus replication in simian peripheral blood leukocytes was demonstrated.

Effect of Dengue Virus Infection on Fc-receptor Functions of Mouse Macrophages

“…The virus also replicates in blood phagocytic cells cultured in vitro . Similar observations have been made in rhesus monkeys with respect to virus isolation from blood monocytes, replication in cultures of spleen, thymus and lymph node macrophages and the distribution of virus antigen in macrophages of different organs (Marchette et al, 1976;Halstead, !981a). In the mouse, dengue virions have been demonstrated in macrophages of spleen (Nath et al, 1983) and virus antigen has been demonstrated in Kupffer cells, and in macrophages of the spleen and peritoneal cavity (Hotta et al, 1981 a, b).…”

Current Research on Dengue

“…aegypti collected as eggs (21). By contrast, no dengue virus was isolated from over 8000 larvae (80 pools) collected from breeding containers in six locations of Jakarta, Indonesia in 1977 (D.J. Gubler, unpublished data) or from over 5000 larvae collected in Bangkok, Thailand (22).…”

“…Several studies have suggested that peripheral blood leucocytes (PBLs) may be a primary site of virus replication (80)(81)(82)(83). If this is the case, detection of infected PBLs by immunofluorescent assay might provide a method for rapid diagnosis of dengue infection.…”

Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody

“…Monkeys monotypically immune to dengue viruses types 1, 3, or 4, when infected with dengue type 2 (D2V), circulated more virus than did nonimmune animals infected with the same virus strain administered by the same route and at the same dose (14). Similarly, PBL cultures prepared from dengue-immune monkeys or human beings readily supported dengue virus (D) replication while leukocyte cultures from non-immunes were not permissive (15)(16)(17). Recently, we have published preliminary evidence that non-neutralizing dengue antibody when added to PBL cultures from nonimmune primates results in productive infections similar to those occurring in cultures of immune PBL (18).…”