Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin

Abstract

UL24 of herpes simplex virus 1 is important for efficient viral replication, but its function is unknown. We generated a recombinant virus, vHA-UL24, encoding UL24 with an N-terminal hemagglutinin tag. By indirect immunofluorescence at 9 h post-infection (hpi), we detected HA-UL24 in nuclear foci and in cytoplasmic speckles. HA-UL24 partially co-localized with nucleolin, but not with ICP8 or coilin, markers for nucleoli, viral replication compartments, and Cajal bodies respectively. HA-UL24 staining was often juxtaposed to that of another nucleolar protein, fibrillarin. Analysis of HSV-1-induced nucleolar modifications revealed that by 18 hpi, nucleolin staining had dispersed, and fibrillarin staining went from clusters of small spots to a few separate but prominent spots. Fibrillarin redistribution appeared to be independent of UL24. In contrast, cells infected with a UL24-deficient virus retained foci of nucleolin staining. Our results demonstrate involvement of UL24 in dispersal of nucleolin during infection.

Differential importance of highly conserved residues in UL24 for herpes simplex virus 1 replication in vivo and reactivation

“…HSV-1 strains were propagated and titrated on Vero cells as described previously (Lymberopoulos & Pearson, 2007). The HSV-1 strains KOS, UL24XG (Jacobson et al, 1998) and tkLTRZ-1 (Davar et al, 1994) were originally provided by D. M. Coen (Harvard Medical School, Boston, MA, USA).…”

“…Transient expression of UL24 homologues from murine gammaherpesvirus 68, Kaposi's sarcoma-associated virus, human cytomegalovirus and HSV-1 induce a G2M cell cycle block (Nascimento & Parkhouse, 2007;Nascimento et al, 2009). UL24 is required for the HSV-1-induced dispersal of nucleolin (Lymberopoulos & Pearson, 2007) and the N-terminal region of UL24 is sufficient to induce the redistribution of this nucleolar protein (Bertrand & Pearson, 2008). More recently, we found that residues corresponding to the putative catalytic domain are especially important for the ability of UL24 to induce this modification of nucleoli.…”

Efficient Induction of Nuclear Aggresomes by Specific Single Missense Mutations in the DNA-binding Domain of a Viral AP-1 Homolog

“…Lytic induction also caused redistribution of nucleolin; rather than being confined to a discrete dot, nucleolin within cells expressing ZEBRA was visibly dispersed. Dispersal of nucleolin also occurs during lytic infection of HSV-1 and is mediated by the UL24 protein (51,52). In cells transfected with Z(R183E), nucleolin was not recruited to aggresomes (supplemental Fig.…”

The major tegument structural protein VP22 targets areas of dispersed nucleolin and marginalized chromatin during productive herpes simplex virus 1 infection

“…These findings suggest that viral replication compartment formation may be responsible for the chromatin marginalization observed. A recent study has shown the involvement of the HSV-1 U L 24 protein in the dispersal of nucleolin (Lymberopoulos and Pearson, 2007). It remains unclear as to whether the alteration of nucleolin is an active process or a secondary consequence of replication compartment formation and/or chromatin marginalization.…”