Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction.
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Authors
Franz, SergejPott, Fabian
Zillinger, Thomas
Schüler, Christiane
Dapa, Sandra
Fischer, Carlo
Passos, Vânia
Stenzel, Saskia
Chen, Fangfang
Döhner, Katinka
Hartmann, Gunther
Sodeik, Beate
Pessler, Frank
Simmons, Graham
Drexler, Jan Felix
Goffinet, Christine
Issue Date
2021-06-02
Metadata
Show full item recordAbstract
Interferon-induced transmembrane (IFITM) proteins restrict membrane fusion and virion internalization of several enveloped viruses. The role of IFITM proteins during alphaviral infection of human cells and viral counteraction strategies are insufficiently understood. Here, we characterized the impact of human IFITMs on the entry and spread of chikungunya virus and Mayaro virus and provide first evidence for a CHIKV-mediated antagonism of IFITMs. IFITM1, 2, and 3 restricted infection at the level of alphavirus glycoprotein-mediated entry, both in the context of direct infection and cell-to-cell transmission. Relocalization of normally endosomal IFITM3 to the plasma membrane resulted in loss of antiviral activity. rs12252-C, a naturally occurring variant of IFITM3 that may associate with severe influenza in humans, restricted CHIKV, MAYV, and influenza A virus infection as efficiently as wild-type IFITM3 Antivirally active IFITM variants displayed reduced cell surface levels in CHIKV-infected cells involving a posttranscriptional process mediated by one or several nonstructural protein(s) of CHIKV. Finally, IFITM3-imposed reduction of specific infectivity of nascent particles provides a rationale for the necessity of a virus-encoded counteraction strategy against this restriction factor.Citation
Life Sci Alliance. 2021 Jun 2;4(7):e202000909. doi: 10.26508/lsa.202000909.Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.Publisher
Life Science AllianceJournal
Life science alliancePubMed ID
34078739Type
ArticleLanguage
enEISSN
2575-1077ae974a485f413a2113503eed53cd6c53
10.26508/lsa.202000909
Scopus Count
The following license files are associated with this item:
- Creative Commons
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