Involvement of the UL24 protein in herpes simplex virus 1-induced dispersal of B23 and in nuclear egress

Abstract

UL24 of herpes simplex virus 1 (HSV-1) is widely conserved within the Herpesviridae family. Herein, we tested the hypothesis that UL24, which we have previously shown to induce the redistribution of nucleolin, also affects the localization of the nucleolar protein B23. We found that HSV-1-induced dispersal of B23 was dependent on UL24. The conserved N-terminal portion of UL24 was sufficient to induce the redistribution of B23 in transient transfection assays. Mutational analysis revealed that the endonuclease motif of UL24 was important for B23 dispersal in both transfected and infected cells. Nucleolar protein relocalization during HSV-1 infection was also observed in non-immortalized cells. Analysis of infected cells by electron microscopy revealed a decrease in the ratio of cytoplasmic versus nuclear viral particles in cells infected with a UL24-deficient strain compared to KOS-infected cells. Our results suggest that UL24 promotes nuclear egress of nucleocapsids during HSV-1 infection, possibly though effects on nucleoli.

Herpes Simplex Virus 1 UL24 Abrogates the DNA Sensing Signal Pathway by Inhibiting NF-κB Activation

“…Based on data from previous reports, UL24 is involved in the dispersal of both nucleolin and B23, and the PD-(D/E)XK endonuclease motif of UL24 is important for this function, although nuclease activity has yet to be demonstrated (41,42,57). However, in this study, the endonuclease motif of UL24 was shown to be dispensable for the inhibition of NF-B activation mediated by cGAS-STING.…”

Interferon, the Cell Cycle and Herpesvirus

“…Thus UL24 must contribute to the observed alteration of the nucleoli in HSV-1 infected cells (Lymberopoulos & Pearson, 2007), a conclusion reinforced by experiments demonstrating that expression of the N-terminal domain of UL24 alone is sufficient to induce the redistribution of nucleolin in the nucleus (Bertrand & Pearson, 2008). A similar impact of UL24 on nucleolar morphology was observed with B23, another abundant nucleolar protein, but not with fibrillarin, which also assumes a diffuse nuclear distribution as a consequence of HSV-1 infection, but in a UL24-independent manner (Callé et al, 2008;Lymberopoulos et al, 2011). Since UL24 is implicated in the redistribution of B23 and nucleolin, it is possible that it plays a role in nuclear egress through its effect on nucleoli, although how nucleolin affects HSV-1 nuclear egress is obscure.…”

“…Since UL24 is implicated in the redistribution of B23 and nucleolin, it is possible that it plays a role in nuclear egress through its effect on nucleoli, although how nucleolin affects HSV-1 nuclear egress is obscure. Finally, the fact that deletion of UL24 conserved homology domains, including the putative endonuclease motifs, resulted in loss of nucleolin and B23 dispersal activity, suggests that this function may be shared among all herpesviruses and must be relevant for the viral life cycle (Bertrand et al, 2010;Bertrand & Pearson, 2008;Lymberopoulos et al, 2011). The first results that demonstrated UL24 involvement with cell cycle manipulation were obtained for ORF20 protein, the UL24 homologue from MHV-68 (Nascimento & Parkhouse, 2007).…”

The nucleolus and herpesviral usurpation

“…VP22 targets the nucleolus and disperses nucleolin and chromatin (Ló pez et al, 2008). UL24 has been reported to induce redistribution of nucleolin and B23 from the nucleolus during HSV-1 infection, promoting nuclear egress of nucleocapsids, possibly through its effect on the nucleolus (Pearson et al, 2011;Lymberopoulos et al, 2011). It has been reported that UL12 protein forms a complex with nucleolin in HSV-1-infected cells (Balasubramanian et al, 2010;Sagou et al, 2010).…”