Project description:The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery.
Project description:Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world’s population at risk. Blocking virus replication in mosquitoes rather than in humans serves as a promising approach to prevent arbovirus transmission, which requires in-depth knowledge of mosquito immunity. By integrating multi-omics data, we identified that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topological associated domain. This Hsf1-sHsp cascade acts as an early response against chikungunya virus (CHIKV) infection and shows pan-antiviral activity in three vector mosquitoes, Aedes aegypti, Aedes albopictus, and Anopheles gambiae. We then assessed the baseline expression of sHsp genes in different tissues of female Ae. aegypti using RNA-seq, and we observed a highly dynamic expression pattern of sHsp genes that varied dramatically across different tissues. Interestingly, sHsp genes were expressed at low levels in two main barrier tissues, the midgut and salivary glands, compared to other tissues such as the crop. Importantly, activation of Hsf1 led to a reduced CHIKV infection rate in adult Ae. aegypti mosquitoes, demonstrating Hsf1 as a promising target for the development of novel intervention strategies to limit arbovirus transmission by mosquitoes.
Project description:The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery. Total small RNAs (miRNAs, siRNAs, piRNAs, etc.) were isolated and sequenced from the heads of sensor strain Aedes aegypti mosquitoes, or from the whole bodies of CHIKV-infected Aedes albopictus mosquitoes 8 hours post infection. Mosquitoes were grown at 18C or 28C in replicates of 1 (Ae. aegypti) or 3 (Ae. albopictus).
Project description:Transcriptome profiling of pyrethroid resistant field populations of Anopheles funestus across Uganda and neighboring Kenya from Uganda and Kenya compared to a susceptible lab strain FANG
Project description:Cellular models have provided significant advances on molecular bases of bipartite interactions between either an arbovirus or a bacterial symbiont with a given arthropod vector. However, although an interference phenomenon was evidenced in tripartite interaction arbovirus-symbiont-mosquito vector very little is known regarding the mechanisms involved. Using large-scale proteome profiling, we characterized proteins differentially expressed in Aedes albopictus cells infected by the symbiotic bacterium Wolbachia and the Chikungunya virus (CHIKV). These proteins were mostly related to cellular processes involved in glycolysis process, protein metabolism, translation and amino acid metabolism. The presence of Wolbachia impacted significantly the protein profiles, including sequestration of proteins such as structural polyprotein and capsid viral proteins that may affect replication and assembly of CHIKV in cellulo. This study provides insights into the molecular pathways involved in the tripartite interaction mosquito-Wolbachia-virus and may help in defining targets for the better implementation of Wolbachia-based strategy for disease transmission control.
Project description:We evaluated transcriptional profiles in peripheral blood mononuclear cells (PBMCs) from 54 pregnant women in Kenya, 19 of whom delivered preterm.
Project description:The emergence of mosquito-borne diseases because of climate change emphasizes the need to study arbovirus-vector protein-protein interactions (PPI) to better understand viral replication and transmission. One such human pathogenic arbovirus is Zika virus (ZIKV; Flaviviridae), transmitted by Aedes aegypti mosquitoes. With the lack of molecular tools to study mosquito cells, we developed an Ae. aegypti AF5 cell line stably expressing ZIKV capsid to investigate PPI through label-free quantification proteomics. We identified 157 interactors with 8 potentially pro-viral during ZIKV infection and showed that the transitional endoplasmic reticulum 94 (TER94) protein of the ubiquitin-proteasome pathway (UPP) was important during ZIKV infection in mosquito cells. Silencing TER94 in AF5 cells prevented ZIKV capsid degradation and significantly reduced the establishment of replication at the early stages of infection. Human TER94 ortholog, valosin containing protein (VCP), identified through ortholog mapping, was found to have a similar function during ZIKV infection in A549 cells. ZIKV had reduced ability to replicate when ubiquitination and VCP function were blocked by chemical inhibitors. Furthermore, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) was identified as a TER94/VCP co-factor for capsid interaction. Our study demonstrates a conserved function for TER94/VCP-UPP during early ZIKV infection in mosquito and human cells.