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IFN-λs inhibit Hantaan virus infection through the JAK-STAT pathway and expression of Mx2 protein

Genes & Immunity volume 20, pages 234–244 (2019)Cite this article

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Abstract

Hantaan virus (HTNV), member of the newly defined Hantaviridae family, within the order Bunyavirales, can cause a hemorrhagic fever with renal syndrome with high fatality rates in humans. However, no specific antiviral agents are currently available for HTNV infection approved by the US Food and Drug Administration. Although interferon lambdas (IFN-λs) have been shown to induce an antiviral state against HTNV, the molecular mechanisms remain to be determined. In this study, we found that IFN-λs exerted its anti-HTNV effect by activating Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway-mediated antiviral immunity in A549 cells. Simultaneously, IFN-λs downregulated suppressor of cytokine signaling proteins, which are the known negative feedback regulators of the JAK-STAT signaling pathway. Additionally, we demonstrated the role of IFN-λs-induced myxovirus resistance 2 (Mx2, also known as MxB) protein as a potential inhibitor for HTNV infection. These findings indicate that IFN-λs play an important role in cellular defenses against HTNV infection at an early stage and that human Mx2 may represent a potential therapeutic target for HTNV infection.

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Acknowledgements

We thank Professor Michael H. Malim (School of Medicine at Guy’s, King’s College, and St Thomas’ Hospitals) for providing the pAHM-shCtrl (CG257), pAHM-shMx2-1 (CG267), and pAHM-shMx2-2 (CG-268) vectors of silencing Mx2. The editorial services provided by Professor Wen-zhe Ho (Temple University School of Medicine) are greatly appreciated. This work was supported by research grants from the National Natural Science Foundation of China (No. 81271819) to WH and (No. 81473036) to YZ.

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    1. State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan,, 430071, Hubei, China

      Ning Li, Fan Luo, Qingzhou Chen, Hui Wang, Linlin Xie, Hairong Xiong, Yong Feng & Wei Hou

    2. Department of Microbiology, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning,, 437100, Hubei, China

      Ni Zhu & Wei Hou

    3. Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing,, 210029, Jiangsu, China

      Ming Yue

    4. Institute of Military Medical Sciences, Nanjing Command, Nanjing,, 210002, Jiangsu, China

      Yun Zhang

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    Li, N., Luo, F., Chen, Q. et al. IFN-λs inhibit Hantaan virus infection through the JAK-STAT pathway and expression of Mx2 protein. Genes Immun 20, 234–244 (2019). https://doi.org/10.1038/s41435-018-0028-x

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