Dengue Virus Multiplication in Cultures of Mouse Peritoneal Macrophages: Effects of Macrophage Activators

Abstract

Dengue-2 virus multiplied in cultures of methylcellulose-induced peritoneal macrophages of BALBjc mice. The in vitro-cultivated macrophages from dengue-I virus-immune mice produced larger amounts of dengue-2 virus than did those from nonimmune controls. The effect of macrophage activators was examined by using nonimmune macrophages. Enhanced virus production was demonstrated in cultures of macrophages pretreated with phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS). The number of virus-infected cells in the pretreated cultures was estimated to be about 0.01 % or less of the total macrophages. Continuous treatment of macrophages with PHA before and after virus inoculation brought about the most marked enhancement of dengue-2 virus multiplication. On the other hand, treatment with concanavalin A or pokeweed mitogen showed little effect on the multiplication of the same virus. Treatment with carrageenan, a specific macrophage blocking agent, markedly suppressed dengue-2 virus production in both dengue-I virus-immune macrophages and LPStreated macrophages. The indirect fluorescent-antibody (FA) technique revealed dengue-2 viral antigen in the cytoplasm of infected macrophages, and the FApositive macrophages were more numerous in PHA-treated cultures than in untreated controls. The results obtained are discussed in relation to a possible role of activated monocytesjmacrophages in the pathogenesis of dengue hemorrhagic fever.

Isolation of Haemorrhagic Fever with Renal Syndrome Virus from Leukocytes of Rats and Virus Replication in Cultures of Rat and Human Macrophages

“…3). It is known from several studies that mitogen-stimulated lymphocytes are permissive for the replication of herpes simplex virus (Nahmias et al, 1964;Westmoreland, 1978;Braun et al, 1984), poliovirus (Willems et al, 1969), measles virus (Joseph et al, 1975;Sullivan et al, 1975) and dengue virus (Theofilopoulos et al, 1976), and also that dengue virus could multiply in cultures of mouse peritoneal macrophages activated with bacterial LPS (Hotta & Hotta, 1982). In this paper, stimulated lymphocytes or macrophages were infected with the B-1 strain of H F R S virus.…”

“…after inoculation. For activation of macrophages, adherent cells were cultured for 3 days with 0.001 mg/ml lipopolysaccharide (LPS) (Difco), which has an ability to stimulate macrophage function (Allison et al, 1973;Hotta & Hotta, 1982), and infected with virus.…”

Dengue Type 2 Virus Infection in Human Peripheral Blood Monocyte Cultures

“…The present study using human monocyte cultures was conducted as an exten sionof our previous studies using mouse macrophage cultures, which showed that D2V production was enhanced by treatment with bacterial cell walls or their structural components (1,20,21), and by addition of diluted anti-DV antibodies (19). In contrast to the mouse macrophage system, D2V production in cultured human monocytes was not affected by bacterial cell wall-related synthetic adjuvants, revealing cell-dependent differences (Table 5).…”

“…In our previous studies (1, 20,21), mouse peritoneal macrophage cultures treated with bacterial cell walls and their structural components showed increased permissiveness to D2V infection. On the other hand, it has been reported that MDP and [B30]-MDP can be effectively used as adjuvants in vaccination against some microbial infections (24).…”

“…We have previously shown that both DV permissiveness and phagocytic activ itiesof mouse macrophages are enhanced by treatment with bacterial components (1, 20,21), and by addition of anti-DV antibodies at subneutralizing concentrations (19). An assumption could be deduced from those results that increase in attach mentand/or endocytosis of DV particles by permissive macrophages results in enhancement of DV infection.…”