Abstract
Understanding the flavivirus infection process in mosquito hosts is important and fundamental in the search for novel control strategies that target the mosquitoes’ ability to carry and transmit pathogenic arboviruses. A group of viruses known as insect-specific viruses (ISVs) has been shown to interfere with the infection and replication of a secondary arbovirus infection in mosquitoes and mosquito-derived cell lines. However, the molecular mechanisms behind this interference are unknown. Therefore, in the present study, we infected the Aedes albopictus cell line U4.4 with either the West Nile virus (WNV), the insect-specific Lammi virus (LamV) or an infection scheme whereby cells were pre-infected with LamV 24 h prior to WNV challenge. The qPCR analysis showed that the dual-infected U4.4 cells had a reduced number of WNV RNA copies compared to WNV-only infected cells. The transcriptome profiles of the different infection groups showed a variety of genes with altered expression. WNV-infected cells had an up-regulation of a broad range of immune-related genes, while in LamV-infected cells, many genes related to stress, such as different heat-shock proteins, were up-regulated. The transcriptome profile of the dual-infected cells was a mix of up- and down-regulated genes triggered by both viruses. Furthermore, we observed an up-regulation of signal peptidase complex (SPC) proteins in all infection groups. These SPC proteins have shown importance for flavivirus assembly and secretion and could be potential targets for gene modification in strategies for the interruption of flavivirus transmission by mosquitoes.
Highlights
Mosquitoes serve as vectors for many viral pathogens, and their associated diseases cause a major health burden across the globe
RNA-sequencing was conducted on poly(A)-enriched RNA extracted from the Ae. albopictus cell line U4.4 infected with either West Nile virus (WNV), insect-specific Lammi virus (LamV) or an infection scheme whereby cells were pre-infected with LamV 24 h before being challenged with WNV
RNA-sequencing was conducted on poly(A)-enriched RNA extracted from the Ae. albopictus cell line U4.4 infected with either WNV, insect-specific LamV or an infection scheme whereby cells were pre-infected with LamV 24 h before being challenged w3 oitfh17 WNV
Summary
Mosquitoes serve as vectors for many viral pathogens, and their associated diseases cause a major health burden across the globe. Flaviviruses, such as the West Nile virus (WNV), Dengue virus (DENV) and Zika virus (ZIKV), impose huge burdens on human and animal health [1,2,3]. For many of these arboviruses, there are no preventive vaccines or therapeutic drugs available and the reduction in transmission relies on traditional methods, e.g., suppressing mosquito populations with insecticides [4]. To find gene modification targets that interfere with the transmission of viral pathogens, we must first study the mechanisms that contribute to vector competence and viral dissemination in the mosquito vector
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