Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti

Christine M. Reitmayer, Emily Levitt, Sanjay Basu, Barry Atkinson, Rennos Fragkoudis, Andres Merits, Sarah Lumley, Will Larner, Adriana V. Diaz, Sara Rooney, Callum J.E. Thomas, Katharina von Wyschetzki, Kai Rausalu, Luke Alphey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1–nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.

Original languageEnglish
Article numbere2303080120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number37
DOIs
Publication statusPublished - 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2023 the Author(s).

Keywords

  • alphaviruses
  • arbovirus transmission
  • nsP2 protease
  • superinfection exclusion

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