A Brief History of the Discovery of RNA-Mediated Antiviral Immune Defenses in Vector Mosquitos

Arthropod-borne viruses (arboviruses) persist in a natural cycle that includes infections of humans or other vertebrates and transmission between vertebrates by infected arthropods, most commonly mosquitos. Arboviruses can cause serious, sometimes fatal diseases in humans and other vertebrates but cause little pathology in their mosquito vectors. SUMMARY Arthropod-borne viruses (arboviruses) persist in a natural cycle that includes infections of humans or other vertebrates and transmission between vertebrates by infected arthropods, most commonly mosquitos. Arboviruses can cause serious, sometimes fatal diseases in humans and other vertebrates but cause little pathology in their mosquito vectors. Knowledge of the interactions between mosquito vectors and the arboviruses that they transmit is an important facet of developing schemes to control transmission. Mosquito innate immune responses to virus infection modulate virus replication in the vector, and understanding the components and mechanisms of the immune response could lead to improved methods for interrupting the transmission cycle. The most important aspect of mosquito antiviral defense is the exogenous small interfering RNA (exo-siRNA) pathway, one arm of the RNA interference (RNAi) silencing response. Our research as well as that of many other groups over the past 25 years to define this pathway are reviewed here. A more recently recognized but less well-understood RNA-mediated mosquito defense against arbovirus infections, the PIWI-interacting RNA (piRNA) pathway, is also described.