Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection

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Abstract
Studies were made on the identity of human and [rhesus] monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1200 rads, were plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10% fetal bovine serum or 100% autologous serum, and were destroyed by incubation with 100 .mu.g/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73% were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from 5 of 5 rhesus monkeys, but not in cell cultures of spleen, thymus or lymph nodes prepared from the same animals. Dengue virus complexed with non-neutralizing antibody is probably internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should be useful as a model for study of immunopathologic mechanisms in human dengue.