A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection

Andrea Troupin, Berlin Londono-Renteria, Michael J. Conway, Erin Cloherty, Samuel Jameson, Stephen Higgs, Dana L. Vanlandingham, Erol Fikrig, Tonya M. Colpitts

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Background Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. Methods We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. Results The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. Conclusions We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. General significance Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector.

Original languageEnglish
Pages (from-to)1898-1909
Number of pages12
JournalBBA - General Subjects
Volume1860
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • Arbovirus
  • Dengue virus
  • Mosquito transmission
  • Protein degradation
  • Ubiquitin

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