@article{mbs:/content/journal/jgv/10.1099/vir.0.017921-0, author = "Leiva-Torres, Gabriel André and Rochette, Pierre-Alexandre and Pearson, Angela", title = "Differential importance of highly conserved residues in UL24 for herpes simplex virus 1 replication in vivo and reactivation", journal= "Journal of General Virology", year = "2010", volume = "91", number = "5", pages = "1109-1116", doi = "https://doi.org/10.1099/vir.0.017921-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.017921-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "The UL24 gene of herpes simplex virus 1 (HSV-1) is widely conserved among all subfamilies of the Herpesviridae. It is one of only four HSV-1 genes for which mutations have been mapped that confer a syncytial plaque phenotype. In a mouse model of infection, UL24-deficient viruses exhibit reduced titres, particularly in neurons, and an apparent defect in reactivation from latency. There are several highly conserved residues in UL24; however, their importance in the role of UL24 in vivo is unknown. In this study, we compared virus strains with substitution mutations corresponding to the PD-(D/E)XK endonuclease motif of UL24 (vUL24-E99A/K101A) or a substitution of another highly conserved residue (vUL24-G121A). Both mutant viruses cause the formation of syncytial plaques at 39 °C; however, we found that the viruses differed dramatically when tested in a mouse model of infection. vUL24-E99A/K101A exhibited titres in the eye that were 10-fold lower than those of the wild-type virus KOS, and titres in trigeminal ganglia (TG) that were more than 2 log10 lower. Clinical signs were barely detectable with vUL24-E99A/K101A. Furthermore, the percentage of TG from which virus reactivated was also significantly lower for this mutant than for KOS. In contrast, vUL24-G121A behaved similarly to the wild-type virus in mice. These results are consistent with the endonuclease motif being important for the role of UL24 in vivo and also imply that the UL24 temperature-dependent syncytial plaque phenotype can be separated genetically from several in vivo phenotypes.", }