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 vitro experiments 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, likely via a 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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Xu-Yang Z,Pei-Yu B,Chuan-Tao Y,Wei Y,Hong-Wei M,Kang T,Chun-Mei Z,Ying-Feng L,Xin W,Ping-Zhong W,Chang-Xing H,Xue-Fan B,Ying Z,Zhan-Sheng Jdoi
10.3389/fimmu.2016.00535subject
Has Abstractpub_date
2017-01-03 00:00:00pages
535issn
1664-3224journal_volume
7pub_type
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