Assessing Aedes aegypti candidate genes during viral infection and Wolbachia-mediated pathogen blocking

Leah T. Sigle, Matthew Jones, Mario Novelo, Suzanne A. Ford, Nadya Urakova, Konstantinos Lymperopoulos, Richard T. Sayre, Zhiyong Xi, Jason L. Rasgon, Elizabeth A. McGraw

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


One approach to control dengue virus transmission is the symbiont Wolbachia, which limits viral infection in mosquitoes. Despite plans for its widespread use in Aedes aegypti, Wolbachia's mode of action remains poorly understood. Many studies suggest that the mechanism is likely multifaceted, involving aspects of immunity, cellular stress and nutritional competition. A previous study from our group used artificial selection to identify a new mosquito candidate gene related to viral blocking; alpha-mannosidase-2a (alpha-Mann-2a) with a predicted role in protein glycosylation. Protein glycosylation pathways tend to be involved in complex host–viral interactions; however, the function of alpha-mannosidases has not been described in mosquito–virus interactions. We examined alpha-Mann-2a expression in response to virus and Wolbachia infections and whether reduced gene expression, caused by RNA interference, affected viral loads. We show that dengue virus (DENV) infection affects the expression of alpha-Mann-2a in a tissue- and time-dependent manner, whereas Wolbachia infection had no effect. In the midgut, DENV prevalence increased following knockdown of alpha-Mann-2a expression in Wolbachia-free mosquitoes, suggesting that alpha-Mann-2a interferes with infection. Expression knockdown had the same effect on the togavirus chikungunya virus, indicating that alpha-Mann-2a may have broad antivirus effects in the midgut. Interestingly, we were unable to knockdown the expression in Wolbachia-infected mosquitoes. We also provide evidence that alpha-Mann-2a may affect the transcriptional level of another gene predicted to be involved in viral blocking and cell adhesion; cadherin87a. These data support the hypothesis that glycosylation and adhesion pathways may broadly be involved in viral infection in Ae. aegypti.

Original languageEnglish (US)
Pages (from-to)356-368
Number of pages13
JournalInsect Molecular Biology
Issue number3
StatePublished - Jun 2022

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Insect Science


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