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Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-α and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.Key words: dengue -apoptosis -monocytes -human The dengue fever emergency has become one of the most dramatic public health issues in Latin America. Epidemics are presenting increased severity and frequency and are continuously expanding geographically (Gubler 2002). In Brazil, the disease is endemic and during the last five years the region has accounted for 70% reported cases in the Americas (Nogueira et al. 2007). Infection with the Dengue virus (DENV) causes a disease spectrum ranging from asymptomatic to shock and hemorrhages, with a risk of lethality. Acute vascular permeability may be followed by abnormal vascular homeostasis. Clinical manifestations include plasmatic leakage, bleeding tendency and liver commitment followed by mild seric transaminase elevation. The physiopathology of the disease may be explained as result of infected monocyte activation by the production of factors that act to increase the vascular permeability and disturb the coagulation system. Pleural effusion, ascites and hemoconcentration are signs of intravascular volume loss. Such factors promote rapid progression to shock (Gibbons & Vaughn 2002).Mononuclear phagocytes are considered the main targets for viral replication (Jessie et al. 2004, NevesSouza et al. 2005). Cells such as B lymphocytes, monocytes, hepatocytes and dendritic cells are described as potential virus targets and may undergo programmed cell death when infected in culture. Reports show apoptotic induction in DENV infected endothelial cells elevates IL-8 and RANTES production, which are chemokines related to inflammatory processes during cell migration (Avirutnan et al. 1...