RT Journal Article
SR Electronic
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
FD Life Science Alliance LLC
SP e202000909
DO 10.26508/lsa.202000909
VO 4
IS 7
A1 Sergej Franz
A1 Fabian Pott
A1 Thomas Zillinger
A1 Christiane Schüler
A1 Sandra Dapa
A1 Carlo Fischer
A1 Vânia Passos
A1 Saskia Stenzel
A1 Fangfang Chen
A1 Katinka Döhner
A1 Gunther Hartmann
A1 Beate Sodeik
A1 Frank Pessler
A1 Graham Simmons
A1 Jan Felix Drexler
A1 Christine Goffinet
YR 2021
UL https://www.life-science-alliance.org/content/4/7/e202000909.abstract
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.