| First Author | Feng S | Year | 2024 |
| Journal | Nat Metab | Volume | 6 |
| Issue | 12 | Pages | 2300-2318 |
| PubMed ID | 39572750 | Mgi Jnum | J:364050 |
| Mgi Id | MGI:8164533 | Doi | 10.1038/s42255-024-01162-0 |
| Citation | Feng S, et al. (2024) Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins. Nat Metab 6(12):2300-2318 |
| abstractText | 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. |
