PT  - JOURNAL ARTICLE
AU  - Sergej Franz
AU  - Fabian Pott
AU  - Thomas Zillinger
AU  - Christiane Schüler
AU  - Sandra Dapa
AU  - Carlo Fischer
AU  - Vânia Passos
AU  - Saskia Stenzel
AU  - Fangfang Chen
AU  - Katinka Döhner
AU  - Gunther Hartmann
AU  - Beate Sodeik
AU  - Frank Pessler
AU  - Graham Simmons
AU  - Jan Felix Drexler
AU  - Christine Goffinet
TI  - Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction
AID  - 10.26508/lsa.202000909
DP  - 2021 Jul 01
TA  - Life Science Alliance
PG  - e202000909
VI  - 4
IP  - 7
4099  - https://www.life-science-alliance.org/content/4/7/e202000909.short
4100  - https://www.life-science-alliance.org/content/4/7/e202000909.full
SO  - Life Sci. Alliance2021 Jul 01; 4
AB  - 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.