Abstract
RNA interference (RNAi)-mediated antiviral immunity is believed to be the primary defense against viral infection in mosquitoes. The production of virus-specific small RNA has been demonstrated in mosquitoes and mosquito-derived cell lines for viruses in all of the major arbovirus families. However, many if not all mosquitoes are infected with a group of viruses known as insect-specific viruses (ISVs), and little is known about the mosquito immune response to this group of viruses. Therefore, in this study, we sequenced small RNA from an Aedes albopictus-derived cell line infected with either Lammi virus (LamV) or Hanko virus (HakV). These viruses belong to two distinct phylogenetic groups of insect-specific flaviviruses (ISFVs). The results revealed that both viruses elicited a strong virus-derived small interfering RNA (vsiRNA) response that increased over time and that targeted the whole viral genome, with a few predominant hotspots observed. Furthermore, only the LamV-infected cells produced virus-derived Piwi-like RNAs (vpiRNAs); however, they were mainly derived from the antisense genome and did not show the typical ping-pong signatures. HakV, which is more distantly related to the dual-host flaviviruses than LamV, may lack certain unknown sequence elements or structures required for vpiRNA production. Our findings increase the understanding of mosquito innate immunity and ISFVs’ effects on their host.
Highlights
Most of our current knowledge on virus interactions with the mosquito vector has come from studies on human pathogenic arboviruses such as West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV)
We found that both Lammi virus (LamV) and Hanko virus (HakV) elicited a strong virus-derived small interfering RNA response that increased over time and targeted the whole viral genome
We showed that two Insect-specific flaviviruses (ISFVs) from two distinct phylogenetic groups can trigger the RNA interference (RNAi) response during an acute infection of the Aedes albopictus U4.4 cell line
Summary
Most of our current knowledge on virus interactions with the mosquito vector has come from studies on human pathogenic arboviruses such as West Nile virus (WNV), Dengue virus (DENV), and Chikungunya virus (CHIKV). Mosquitoes are often naturally and persistently infected with a group of viruses that are known as insectspecific viruses (ISVs). This group of viruses are unable to infect vertebrates and are maintained in the mosquito population through vertical transmission from mother to offspring [1,2,3,4]. Phylogenetic analyses have shown that many ISVs belong to viral families associated with pathogenic arboviruses such as Flaviviridae, Togaviridae, and Peribunyaviridae [5,6]. Insect-specific flaviviruses (ISFVs) can further be divided into two distinct phylogenetic subgroups. Two members of the insect-specific flavivirus group are Lammi virus (LamV) and Hanko virus (HakV), which were both isolated from mosquitoes in Finland
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