Journal
JOURNAL OF VIROLOGY
Volume 87, Issue 15, Pages 8451-8464Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.03382-12
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Funding
- Defense Threat Reduction Agency (DTRA)
- Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]
- Faculty Research Participation Program at the U.S. Army Medical Research and Materiel Command
- NIAID [HHSN272200200016I]
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We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-alpha), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-alpha against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.
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