title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.
abstract: Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients.In vitroexperiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likelyviaa mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu-Yang
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Bian
authors.initials: B
authors.lastname: Pei-Yu
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chuan-Tao
authors.affiliation: Department of Microbiology, Fourth Military Medical University , Xi'an , China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Microbiology, Fourth Military Medical University , Xi'an , China.
authors.forename: Ma
authors.initials: M
authors.lastname: Hong-Wei
authors.affiliation: Department of Immunology, Fourth Military Medical University , Xi'an , China.
authors.forename: Tang
authors.initials: T
authors.lastname: Kang
authors.affiliation: Department of Immunology, Fourth Military Medical University , Xi'an , China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Chun-Mei
authors.affiliation: Department of Microbiology, Fourth Military Medical University , Xi'an , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ying-Feng
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ping-Zhong
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Huang
authors.initials: H
authors.lastname: Chang-Xing
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Bai
authors.initials: B
authors.lastname: Xue-Fan
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhan-Sheng
keywords: Hantaan virus; hemorrhagic fever with renal syndrome; interferon-induced transmembrane protein 3; negative regulator of interferon response; single nucleotide polymorphisms