Identifying the diverse functionalities and characteristics of the RNAi response against arthropod-borne viruses in mosquitoes

Abstract

Mosquitoes are known as important vectors of several arthropod-borne (arbo)viruses causing severe diseases in humans like West Nile Virus, Dengue virus or Zika virus. Although they often cause severe clinical manifestations in their vertebrate hosts, no apparent pathology is seen in their mosquito vector despite high viral replication levels, indicating an effective immune response against arboviruses in the mosquito vector. However, arbovirus infection generally result in a persistent infection, indicating the inability of the mosquito immune response to clear these viral infections. The mechanism of RNA interference (RNAi) is a sequence-specific RNA degradation system that is known to act antiviral in a variety of organisms like plants and invertebrates. Three different pathways based on different classes of small RNAs are associated with RNAi: the microRNA, small-interfering RNA (siRNA) and PIWI-interacting RNA (piRNA) pathway. The exogenous siRNA (exo-siRNA) pathway is believed to be the main antiviral defense in arthropods, including mosquitoes and has been shown to be linked to vector competence. The role of small RNAs in controlling arbovirus infection in mosquitoes and in shaping vector competence is widely recognized but the underlying mechanisms remain unknown. It also seems to be highly specific with regard to the virus species and the stage of infection. This study was designed to investigate the characteristics of the RNAi response against different arbovirus infections in vector mosquitoes during the acute and persistent infection phase.