期刊
JOURNAL OF VIROLOGY
卷 86, 期 24, 页码 13697-13707出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01828-12
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资金
- Canadian Institutes for Health Research
- Chinese Ministry of Health [2012ZX 10001-006]
- 973 program [2010CB534907]
- CSC (China Scholarship Council) State Scholarship Fund
Interferon-inducible transmembrane (IFITM) protein family members IFITM1, -2, and -3 restrict the infection of multiple enveloped viruses. Significant enrichment of a minor IFITM3 allele was recently reported for patients who were hospitalized for seasonal and 2009 H1N1 pandemic flu. This IFITM3 allele lacks the region corresponding to the first amino-terminal 21 amino acids and is unable to inhibit influenza A virus. In this study, we found that deleting this 21-amino-acid region relocates IFITM3 from the endosomal compartments to the cell periphery. This finding likely underlies the lost inhibition of influenza A virus that completes its entry exclusively within endosomes at low pH. Yet, wild-type IFITM3 and the mutant with the 21-amino-acid deletion inhibit HIV-1 replication equally well. Given the pH-independent nature of HIV-1 entry, our results suggest that IFITM3 can inhibit viruses that enter cells via different routes and that its N-terminal region is specifically required for controlling pH-dependent viruses.
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