Abstract
The genus Flavivirus contains more than 70 single-stranded, positive-sense arthropod-borne RNA viruses. Some flaviviruses are particularly medically important to humans and other vertebrates including dengue virus (DENV), West Nile virus, and yellow fever virus. These viruses are transmitted to vertebrates by mosquitoes and other arthropod species. Mosquitoes are also infected by insect-specific flaviviruses (ISFs) that do not appear to be infective to vertebrates. Cell fusing agent virus (CFAV) was the first described ISF, which was discovered in an Aedes aegypti cell culture. We found that while CFAV infection could be significantly reduced by application of RNAi against the NS5 gene, removal of the treatment led to quick restoration of CFAV replication. Interestingly, we found that CFAV infection significantly enhanced replication of DENV, and vice versa, DENV infection significantly enhanced replication of CFAV in mosquito cells. We have shown that CFAV infection leads to increase in the expression of ribonuclease kappa (RNASEK), which is known to promote infection of viruses that rely on endocytosis and pH-dependent entry. Knockdown of RNASEK by dsRNA resulted in reduced DENV replication. Thus, increased expression of RNASEK induced by CFAV is likely to contribute to enhanced DENV replication in CFAV-infected cells.
Highlights
Flaviviruses have single-stranded positive sense RNA genomes and are transmitted to vertebrate species mostly by mosquitoes and other arthropods[1]
We investigated the presence of Cell fusing agent virus (CFAV) in Ae. aegypti cell lines available to us by reverse transcription (RT)-polymerase chain reaction (PCR) with CFAV-specific detection primers
In Culex pipiens, Culex flavivirus (CxFV) suppressed dissemination of West Nile virus (WNV) at early stages of infection (7 days), which may affect the severity of enzootic transmission of WNV by the mosquito[28, 29]
Summary
Flaviviruses have single-stranded positive sense RNA genomes and are transmitted to vertebrate species mostly by mosquitoes and other arthropods[1]. Cell fusing agent virus (CFAV) was the first described ISF discovered from an Ae. aegypti cell line[3]. While coinfections or superinfections (sequential infections) of a variety of homologous or heterologous arboviruses has been tested in different insect cell lines (mostly in C6/36 cells) and mosquitoes (reviewed in refs 7 and 8), none of these studies included CFAV. In these studies, the outcomes of coinfections or superinfections were either negative or no interference. We investigated infection of Ae. aegypti cell lines, Aag[2] and Aa20, with CFAV and explored the interaction of CFAV with DENV
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