Chikungunya virus superinfection exclusion is mediated by a block in viral replication and does not rely on non-structural protein 2

dc.contributor.authorBoussier, Jeremyen
dc.contributor.authorLevi, Laura I.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorPoirier, Enzo Z.en
dc.contributor.authorVignuzzi, Marcoen
dc.contributor.authorAlbert, Matthew L.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.description.abstractSuperinfection exclusion (SIE) is a process by which a virally infected cell is protected from subsequent infection by the same or a closely related virus. By preventing cell coinfection, SIE favors preservation of genome integrity of a viral strain and limits its recombination potential with other viral genomes, thereby impacting viral evolution. Although described in virtually all viral families, the precise step(s) impacted by SIE during the viral life cycle have not been systematically explored. Here, we describe for the first time SIE triggered by chikungunya virus (CHIKV), an alphavirus of public health importance. Using single-cell technologies, we demonstrate that CHIKV excludes subsequent infection with: CHIKV; Sindbis virus, a related alphavirus; and influenza A, an unrelated RNA virus. We further demonstrate that SIE does not depend on the action of type I interferon, nor does it rely on host cell transcription. Moreover, exclusion is not mediated by the action of a single CHIKV protein; in particular, we observed no role for non-structural protein 2 (nsP2), making CHIKV unique among characterized alphaviruses. By stepping through the viral life cycle, we show that CHIKV exclusion occurs at the level of replication, but does not directly influence virus binding, nor viral structural protein translation. In sum, we characterized co-infection during CHIKV replication, which likely influences the rate of viral diversification and evolution.en
dc.description.notesThis work was funded by the Agence nationale de la recherche, the DARPA INTERCEPT program managed by Jim Gimlett and Bradley Ringeisen, and administered through DARPA Cooperative Agreement #HR0011-17-2-0023 to M. V. (the content of the information does not necessarily reflect the position or the policy of the US government, and no official endorsement should be inferred). J.B. was supported by a grant from the Ecole normale superieure and by the ecole doctorale Frontieres du vivant -programme Bettencourt. Insitro provided support in the form of salaries for M.L.A. The specific roles of these authors are articulated in the author contributions' section. None of the funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipDARPAUnited States Department of DefenseDefense Advanced Research Projects Agency (DARPA) [HR0011-17-2-0023]; Ecole normale superieure; ecole doctorale Frontieres du vivant -programme Bettencourt; Agence nationale de la rechercheFrench National Research Agency (ANR); DARPA INTERCEPT programen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleChikungunya virus superinfection exclusion is mediated by a block in viral replication and does not rely on non-structural protein 2en
dc.title.serialPLoS Oneen
dc.typeArticle - Refereeden


Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
3.01 MB
Adobe Portable Document Format