Mosquito-borne viral pathogens infect millions of people worldwide, often resulting in fatal infections. Our research interests in mosquito vector biology focuses on understanding of the molecular and genetic basis of mosquito resistance to arbovirus infections. Unlike mammalian cells including humans, for instance, mosquito cells do not show pathologic symptoms when infected by arboviruses. This observation led us to embarking a microarray study to investigate mosquito-virus interactions using Anopheles gambiae and o’nyong-nyong virus (ONNV) as a model system. As a result, we found that transcription of the hsc70B gene is increased about 2.6-fold in ONNV-infected An. gambiae compared to non-infected controls. Subsequently, in vivo RNAi silencing of the hsc70B transcript caused enhanced ONNV replication in female mosquitoes. Therefore, these results suggest that the hsc70B protein has an inhibitory effect on ONNV replication. A promoter analysis of the hsc70B locus further demonstrated that the hsc70B promoter is able to induce transcription of hsc70B in response to ONNV infection. In addition, hsc70B transcription was also induced by West Nile or La Crosse virus infection. Collectively, our findings indicate that hsc70B plays a role in suppressing virus replication as a general antiviral mechanism. Implications of hsc70B research and our other research endeavors toward the control of mosquito-borne infectious diseases will be discussed.