Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.

Autor: Feng S; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.; Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA., Xie N; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.; 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, PR China., Liu Y; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Qin C; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Savas AC; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Wang TY; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USA., Li S; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Rao Y; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Shambayate A; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Chou TF; Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, CA, USA., Brenner C; Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope, Duarte, CA, USA., Huang C; 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, PR China., Feng P; Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. pinghuif@usc.edu.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2024 Dec; Vol. 6 (12), pp. 2300-2318. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s42255-024-01162-0
Abstrakt: As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD + ) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD + synthesis. Proteomics analysis of HSV-1-infected cells identifies phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins, which are de-phosphoribosylated by NAMPT 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. Loss of NAMPT renders mice highly susceptible to HSV-1 infection. Our work describes an additional enzymatic activity of a metabolic enzyme in viral infection and host defence, offering a system to interrogate the roles of protein phosphoribosylation in metazoans.
Competing Interests: Competing interests: C.B. is a chief scientific advisor of ChromaDex and co-founder of Alphina Therapeutics. P.F. is a consultant for Marc J Bern & Partners. All other authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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