Immune priming can prevent WNV establishment in Culex quinquefasciatus mosquitoes: evidence for immune priming based reversal of WNV-mediated immune suppression.

Abstract

Mosquito-borne infectious diseases cause wide-spread loss of life and livelihood often in low-income settings. However, control of mosquito-vectored viral diseases such as West Nile virus (WNV) and Japanese encephalitis virus (JEV) remains challenging. Here we use an existing feature of the insect immune system to effectively vaccinate Culex quinquefasciatus mosquitoes against WNV infection. We find that priming mosquitoes by exposure to inactivated WNV reduces their likelihood of developing transmissible infections of WNV after live infection. We used RNA sequencing to identify gene expression in response to WNV and JEV infection, and the role of prior priming exposure on constitutive and induced expression on infection. Infection with either Flavivirus causes broad suppression of gene expression. WNV and JEV infection resulted in suppression of different suites of genes with notable immune genes, such as antimicrobial peptides, being strongly suppressed on WNV infection. We hypothesise that the increased resistance to WNV infection seen in primed mosquitoes may be the result of priming nullifying the immune suppression found in non-primed WNV-fed mosquitoes, potentially through greater expression of mRNA regulatory genes such as cap-binding proteins in primed mosquitoes. Author summaryMosquitoes vector many devastating infectious diseases. Two such vectored viral diseases are West Nile virus (WNV) and Japanese encephalitis virus (JEV). Control of these diseases remains challenging, and no vaccine exists for WNV. Here, we tested whether we could instead vaccinate the mosquitoes against WNV. By injecting mosquitoes with dead WNV we found that we could reduce the number of infected mosquitoes by half. We then used whole-genome RNA sequencing to identify which genes are transcribed, which will help us understand genes that are important for this form of insect immune priming, and for responses to normal WNV and JEV infection. We found that WNV suppresses the expression of many immune genes but these genes are expressed normally in vaccinated mosquitoes. Our findings expand our understanding of mosquito infection with these viruses but also demonstrate how prior exposure to a disease can produce lasting protection.