Extended Data Fig. 10: Phosphoribose of structural proteins promotes HSV-1 entry and replication.
From: Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins
a, Entry analysis of HSV-1 virions treated with NAMPT or NAMPT-H247E, with or without ATP (2 mM), n = 3. Statistical significance was calculated using unpaired two-tailed t-tests, P < 0.0001 ( + ATP, UL37), P = 0.0031 ( + ATP, UL48), P = 0.1455 (-ATP, UL37), P = 0.5709 (-ATP, UL48). b, Two-dimensional gel electrophoresis and immunoblotting analysis of HSV-1 virions treated with wildtype NAMPT (WT), the NAMPT-H247E mutant or TARG1 with antibody against gB. Red arrows indicate the new species produced by NAMPT or TARG1 treatment. c, Quantification of NAM, NMN and phosphoribose in the supernatant of the in vitro phosphoribosylase reactions by mass spectrometry, n = 3. Statistical significance was calculated using unpaired two-tailed t-tests, P < 0.0001 for NAMPT + HSV-1 group versus NAMPT + PRPP group in NAM and phosphoribose analysis. ND, not detected. d, Summary of biochemical and functional characterization of the site-specific phosphoribosylation of HSV-1 proteins. Red arrows indicate the residues whose phosphoribosylation-resistant mutations displayed significant effect on HSV-1 infection. Intensity of colour indicates the degree of effect and open circles indicate no phenotype. Statistical significance was calculated using unpaired two-tailed Student’s t-tests and two-way ANOVA analysis. Data in a and c are presented as mean values\(\pm\)SD.
