The ability of herpes simplex virus type 1 immediate-early protein Vmw110 to bind to a ubiquitin-specific protease contributes to its roles in the activation of gene expression and stimulation of virus replication.
Herpes simplex virus type 1 immediate-early protein Vmw110 stimulates the onset of virus infection and is required for efficient reactivation from latency. In transfection assays, Vmw110 is a potent activator of gene expression, but its mode of action has yet to be determined. Previous work has shown that Vmw110 localizes to specific intranuclear structures known as ND10, PML bodies, or PODs and causes the disruption of these domains. The ability of Vmw110 to disrupt ND10 correlates with its biological activities in infected and transfected cells. It has also been found that Vmw110 binds strongly and specifically to a ubiquitin-specific protease known as HAUSP, itself a component of a subset of ND10. In this study we have investigated the role of HAUSP in Vmw110 activity; single amino acid residues of Vmw110 required for the interaction were identified, and the effects of mutation of these residues in infected and transfected cells were then assayed. The results indicate that the ability to bind to HAUSP contributes to the functional activities of Vmw110.
Everett
R D
RD
MRC Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom. r.everett@vir.gla.ac.uk
Meredith
M
M
Orr
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D010450:Endopeptidases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D011817:Rabbits; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7; D014779:Virus Replication
D017874:Immediate-Early Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7