Alphavirus restriction by IFITM proteins
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Interferon inducible transmembrane proteins (IFITMs) are broad‐spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo‐, flavi‐, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid‐induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus. IFITM3 inhibits release of the SFV capsid into the cytosol, without inhibiting binding, internalization, trafficking to endosomes or low pH‐induced conformational changes in the envelope glycoprotein. Infection by SFV fusion at the cell surface was inhibited by IFITM1, but was equally inhibited by IFITM3. Furthermore, an IFITM3 mutant (Y20A) that is localized to the plasma membrane inhibited infection by cell surface fusion more potently than IFITM1. Together, these results indicate that IFITMs, in particular IFITM3, can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. That IFITM3 can restrict SFV infection by fusion at the cell surface equivalently to IFITM1 suggests that IFITM3 has greater antiviral potency against SFV.
Date Issued
2016-09-01
Date Acceptance
2016-05-09
Citation
Traffic, 2016, 17 (9), pp.997-1013
ISSN
1398-9219
Publisher
Wiley
Start Page
997
End Page
1013
Journal / Book Title
Traffic
Volume
17
Issue
9
Copyright Statement
© 2016 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387181300003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
alphavirus
IFITM
interferon inducible transmembrane protein
restriction factor
Semliki Forest virus
SFV
virus entry
virus-host interaction
SEMLIKI-FOREST-VIRUS
WEST NILE VIRUS
DENGUE VIRUS
TRANSMEMBRANE PROTEIN-3
VIRAL ENTRY
CELLS
FUSION
BHK-21-CELLS
LOCALIZATION
REPLICATION
Publication Status
Published
Date Publish Online
2016-06-24