Abstract
BackgroundAnopheles mosquitoes are efficient vectors of human malaria, but it is unknown why they do not transmit viruses as well as Aedes and Culex mosquitoes. The only arbovirus known to be consistently transmitted by Anopheles mosquitoes is O’nyong nyong virus (ONNV, genus Alphavirus, family Togaviridae). The interaction of Anopheles mosquitoes with RNA viruses has been relatively unexamined.ResultsWe transcriptionally profiled the African malaria vector, Anopheles coluzzii, infected with ONNV. Mosquitoes were fed on an infectious bloodmeal and were analyzed by Illumina RNAseq at 3 days post-bloodmeal during the primary virus infection of the midgut epithelium, before systemic dissemination. Virus infection triggers transcriptional regulation of just 30 host candidate genes. Most of the regulated candidate genes are novel, without known function. Of the known genes, a significant cluster includes candidates with predicted involvement in carbohydrate metabolism. Two candidate genes encoding leucine-rich repeat immune (LRIM) factors point to possible involvement of immune protein complexes in the mosquito antiviral response. The primary ONNV infection by bloodmeal shares little transcriptional response in common with ONNV infection by intrathoracic injection, nor with midgut infection by the malaria parasites, Plasmodium falciparum or P. berghei. Profiling of A. coluzzii microRNA (miRNA) identified 118 known miRNAs and 182 potential novel miRNA candidates, with just one miRNA regulated by ONNV infection. This miRNA was not regulated by other previously reported treatments, and may be virus specific. Coexpression analysis of miRNA abundance and messenger RNA expression revealed discrete clusters of genes regulated by Imd and JAK/STAT, immune signaling pathways that are protective against ONNV in the primary infection.ConclusionsONNV infection of the A. coluzzii midgut triggers a remarkably limited gene regulation program of mostly novel candidate genes, which likely includes host genes deployed for antiviral defense, as well as genes manipulated by the virus to facilitate infection. Functional dissection of the ONNV-response candidate genes is expected to generate novel insight into the mechanisms of virus-vector interaction.
Highlights
Anopheles mosquitoes are efficient vectors of human malaria, but it is unknown why they do not transmit viruses as well as Aedes and Culex mosquitoes
Differential A. coluzzii messenger RNA (mRNA) transcript abundance during O’nyong-nyong virus (ONNV) infection The primary infection of ONNV in the mosquito midgut after an infectious bloodmeal is controlled by antiviral mechanisms largely distinct from those active in the subsequent disseminated systemic infection [6]
To identify candidate antiviral factors and immune pathways solicited during the primary midgut infection, we fed mosquitoes on an ONNV-containing bloodmeal or control normal bloodmeal, purified RNA three days post-bloodmeal before virus dissemination to the systemic compartment, and transcriptionally profiled mRNA abundance by Illumina RNA sequencing (RNAseq)
Summary
Anopheles mosquitoes are efficient vectors of human malaria, but it is unknown why they do not transmit viruses as well as Aedes and Culex mosquitoes. The only arbovirus known to be consistently transmitted by Anopheles mosquitoes is O’nyong nyong virus (ONNV, genus Alphavirus, family Togaviridae). O’nyong-nyong virus (ONNV) and Chikungunya virus (CHIKV) are closely related alphaviruses of the Semliki Forest virus complex [1]. Both viruses cause febrile illness in humans and the symptoms are hard to distinguish from other alphavirus infections, Dengue fever or malaria [2]. More research effort has been focused on Aedes mosquitoes, due to their ability to transmit multiple arboviruses such as dengue or Zika (Flaviviruses), which has led to a relative neglect about Anopheles interactions with arboviruses
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