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Obesity's Unexpected Influence: Reduced Alphavirus Transmission and Altered Immune Activation in the Vector
Pallavi Rai1,2, Emily M Webb2,3, Sally L Paulson3
1Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, Virginia, USA.
Journal of Medical Virology
|October 28, 2024
Summary
Obesity in vertebrate hosts impacts mosquito-borne alphavirus transmission by altering mosquito immune and metabolic genes. Identifying these host-dependent factors may lead to new antiviral strategies against viruses like Chikungunya virus (CHIKV) and Mayaro virus (MAYV).
Area of Science:
- Virology
- Immunology
- Entomology
- Genetics
Background:
- Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are significant alphaviruses causing outbreaks in the Americas, transmitted by Aedes mosquitoes.
- Virus-host-vector interactions are crucial for epidemic potential, yet host factors influencing alphavirus transmission remain understudied.
- Previous research indicated that host obesity reduces alphavirus transmission by mosquitoes.
Purpose of the Study:
- To investigate how alphavirus-infected obese bloodmeals alter mosquito immune genes and pathways, inhibiting virus transmission.
- To identify specific genes and pathways in mosquitoes that influence alphavirus transmission.
- To explore the potential for novel antiviral strategies based on host-dependent transmission factors.
Main Methods:
- RNA sequencing (RNA-seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to analyze midgut RNA from mosquitoes fed on infected lean and obese mouse bloodmeals.
- Gene knockdown studies were performed to validate the roles of identified genes in alphavirus transmission.
- Comparative analysis of gene expression profiles between mosquitoes fed on lean versus obese bloodmeals.
Main Results:
- Mosquitoes fed on alphavirus-infected obese bloodmeals showed upregulation of the Toll pathway and downregulation of metabolic genes.
- Gene knockdown confirmed the Toll pathway's antiviral role in alphavirus transmission.
- AAEL009965 and fatty acid synthase (FASN) were identified as having proviral roles in alphavirus transmission.
Conclusions:
- Host obesity influences mosquito immune gene expression, impacting alphavirus transmission.
- The Toll pathway acts antagonistically to alphavirus transmission, while AAEL009965 and FASN promote it.
- This research provides a framework for developing broad-spectrum antivirals against mosquito-borne viruses by targeting identified host-dependent factors, potentially through genetically modified mosquitoes.
