TY - JOUR T1 - Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000909 VL - 4 IS - 7 SP - e202000909 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 Y1 - 2021/07/01 UR - https://www.life-science-alliance.org/content/4/7/e202000909.abstract N2 - 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. ER -