Aedes aegyptiSalivary Gland Extracts Modulate Anti-Viral and TH1/TH2 Cytokine Responses to Sindbis Virus Infection

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Abstract
Vector-borne viruses are naturally transmitted when a vector salivates during feeding on a vertebrate host. Most laboratory studies of infection disregard the role that the vector plays in the pathogenesis of the virus. In this study, intradermal inoculations of Aedes aegypti salivary gland extract (SGE) and Sindbis virus (SINV) were used to investigate the effect of mosquito feeding on the vertebrate immune response to infection with an arthropod-borne virus. Murine cytokine expression in the skin was quantified by means of real-time RT-PCR. In response to co-inoculation of SINV with SGE, interferon (IFN)-β expression at 24 and 72 h post inoculation was significantly reduced by 2.2- and 2.3-fold, respectively, when compared to injection of virus alone. IFN-γ expression in response to SINV infection was significantly decreased by 1.6-fold at 24 h post inoculation when SGE was co-inoculated. In contrast, interleukin (IL)–4 expression was significantly up regulated when SGE was co-inoculated at 24 h post inoculation becoming a 3.3-fold increase by 72 h post inoculation. Compared to expression with SINV alone, IL-10 expression showed a 7.6-fold increase by 72 h post inoculation in mice receiving SGE concurrently with virus. This study suggests that the response to virus is significantly different when an infection is initiated in the presence of mosquito salivary factors, and we identify a possible mechanism for potentiation of viral infections initiated by the natural mosquito vector or in the presence of mosquito saliva.