<em>Anopheles gambiae</em> Antiviral Immune Response to Systemic O'nyong-nyong Infection

<div><h3>Background</h3><p>Mosquito-borne viral diseases cause significant burden in much of the developing world. Although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. In contrast to mosquitoes of the Aedes and Culex genera, <em>Anopheles gambiae</em>, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is O'nyong-nyong virus (ONNV). Here we have investigated the <em>A. gambiae</em> immune response to systemic ONNV infection using forward and reverse genetic approaches.</p> <h3>Methodology/Principal Findings</h3><p>We have used DNA microarrays to profile the transcriptional response of <em>A. gambiae</em> inoculated with ONNV and investigate the antiviral function of candidate genes through RNAi gene silencing assays. Our results demonstrate that <em>A. gambiae</em> responses to systemic viral infection involve genes covering all aspects of innate immunity including pathogen recognition, modulation of immune signalling, complement-mediated lysis/opsonisation and other immune effector mechanisms. Patterns of transcriptional regulation and co-infections of <em>A. gambiae</em> with ONNV and the rodent malaria parasite <em>Plasmodium berghei</em> suggest that hemolymph immune responses to viral infection are diverted away from melanisation. We show that four viral responsive genes encoding two putative recognition receptors, a galectin and an MD2-like receptor, and two effector lysozymes, function in limiting viral load.</p> <h3>Conclusions/Significance</h3><p>This study is the first step in elucidating the antiviral mechanisms of <em>A. gambiae</em> mosquitoes, and has revealed interesting differences between <em>A. gambiae</em> and other invertebrates. Our data suggest that mechanisms employed by <em>A. gambiae</em> are distinct from described invertebrate antiviral immunity to date, and involve the complement-like branch of the humoral immune response, supressing the melanisation response that is prominent in anti-parasitic immunity. The antiviral immune response in <em>A. gambiae</em> is thus composed of some key conserved mechanisms to target viral infection such as RNAi but includes other diverse and possibly species-specific mechanisms.</p>