title: Hantaan virus can infect human keratinocytes and activate an interferon response through the nuclear translocation of IRF-3.
abstract: Hantaan virus (HTNV) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (HFRS) in Asia and can be transmitted to humans through bites or the inhalation of aerosolized urine, droppings, or saliva of infected rodents. Keratinocytes predominate in the epidermis and reportedly serve as a replication site for multiple vector-borne viruses, little is known about the susceptibility of human skin cells to HTNV infection. Therefore, we aimed to evaluate whether human keratinocytes support HTNV replication and elicit an immune response against HTNV infection. We found that a human keratinocyte cell line, HaCaT, supports HTNV replication. In addition, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (MDA5) play key roles in the detection of HTNV infection in HaCaT cells and in the up-regulation of interferon (IFN)-β expression, which subsequently leads to the production of a large amount of antiviral interferon-stimulated genes (ISGs) and other chemokines used for immune cell recruitment. Furthermore, we suggest that interferon regulatory factor (IRF)-3, as opposed to NF-κB/p65 or IRF-7, is translocated to the nucleus to induce IFN-β. However, the early induction of chemokine CXCL10 was a direct result of HaCaT cells counteracting HTNV infection and was not due to the induction of IFN. Overall, our data demonstrate, for the first time, the permissiveness of human keratinocytes to HTNV infection.
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China; Clinical Laboratory, 323 Hospital of The People's Liberation Army, Lanzhou Military Region, Xian, Shaanxi 710054, China.
authors.forename: Yongni
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Xingan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China. Electronic address: yflei@fmmu.edu.cn.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Microbiology, Faculty of Preclinical Medicine, The Fourth Military Medical University, Xian, Shaanxi 710032, China. Electronic address: flzhang@fmmu.edu.cn.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005786:Gene Expression Regulation; D018063:Hantaan virus / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014779:Virus Replication
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D016899:Interferon-beta; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Hantaan virus; IFN-stimulated genes; IFN-β; IRF-3; Keratinocyte