The N-terminal region of IFITM3 modulates its antiviral activity by regulating IFITM3 cellular localization.
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.
Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, China.
Rui
R
Jia
Qinghua
Q
Pan
Shilei
S
Ding
Liwei
L
Rong
Shan-Lu
SL
Liu
Yunqi
Y
Geng
Wentao
W
Qiao
Chen
C
Liang
D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D011992:Endosomes / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009975:Orthomyxoviridae / Q000502:physiology; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
D017931:DNA Primers; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins