Transcriptome analysis of an Aedes albopictus cell line single and dual infected with Lammi virus and WNV

Understanding the flavivirus infection process in the mosquito host 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) have shown to interfere with the infection and replication of a secondary arbovirus infection in mosquitoes and mosquito derived cell lines. Therefore, in the present study, we have Infected the Aedes albopictus cell line U4.4 with either West Nile virus (WNV), the insect-specific Lammi virus (LamV) or an infection scheme where cells were pre-infected with LamV 24 h prior to WNV challenge. qPCR analysis of supernatant showed that the dual infected U4.4 cells had a reduced replication of WNV compared to only WNV infected cells. The Transcriptome profiles of the different infection groups showed a variety of altered genes. The WNV infected cells showed an upregulation of a broad range of immune related proteins, while the LamV infected cells showed genes related to stress such as different heat shock proteins. The transcriptome profile of the dual-infected cells showed a mix of up and downregulated genes triggered by both viruses, which was more similar to the one of WNV infected cells in the early time point but shifted towards the one of LamV infected cells in the later time point. We could also observe an upregulation of endoplasmic reticulum-associated signal peptidase complex (SPC) proteins in common between all infection groups. These SPC proteins have shown to be important for flavivirus assembly and secretion and could be potential targets for gene modification in strategies for interruption of flavivirus transmission by mosquitoes.