机构：[1]Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.[2]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China, School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.四川大学华西医院[3]Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.[4]Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
As obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+ synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+ synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT de-phosphoribosylates viral proteins in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.
语种：
外文
PubmedID：
第一作者：
第一作者机构：[1]Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.[4]Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
共同第一作者：
通讯作者：
通讯机构：[1]Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.[*1]Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
推荐引用方式(GB/T 7714)：
Zhang Shu,Xie Na,Liu Yongzhen,et al.The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection[J].bioRxiv : the preprint server for biology.2023,doi:10.1101/2023.10.12.562112.
APA：
Zhang Shu,Xie Na,Liu Yongzhen,Qin Chao,Savas Ali Can...&Feng Pinghui.(2023).The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection.bioRxiv : the preprint server for biology,,
MLA：
Zhang Shu,et al."The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection".bioRxiv : the preprint server for biology .(2023)
