Alphaherpesvirus proteins related to herpes simplex virus type 1 ICP0 affect cellular structures and proteins.
The herpes simplex virus type 1 (HSV-1) immediate-early protein ICP0 interacts with several cellular proteins and induces the proteasome-dependent degradation of others during infection. In this study we show that ICP0 is required for the proteasome-dependent degradation of the ND10 protein Sp100 and, as with the other target proteins, the ICP0 RING finger domain is essential. Further, comparison of the kinetics and ICP0 domain requirements for the degradation of PMI and Sp100 suggests that a common mechanism is involved. Homologues of ICP0 are encoded by other members of the alphaherpesvirus family. These proteins show strong sequence homology to ICP0 within the RING finger domain but limited similarity elsewhere. Using transfection assays, we have shown that all the ICP0 homologues that we tested have significant effects on the immunofluorescence staining character of at least one of the proteins destabilized by ICP0, and by using a recombinant virus, we found that the equine herpesvirus ICP0 homologue induced the proteasome-dependent degradation of endogenous CENP-C and modified forms of PML and Sp100. However, in contrast to ICP0, the homologue proteins had no effect on the distribution of the ubiquitin-specific protease USP7 within the cell, consistent with their lack of a USP7 binding domain. We also found that ICP0 by itself could induce the abrogation of SUMO-1 conjugation and then the proteasome-dependent degradation of unmodified exogenous PML in transfected cells, thus demonstrating that other HSV-1 proteins are not required. Surprisingly, the ICP0 homologues were unable to cause these effects. Overall, these data suggest that the members of the ICP0 family of proteins may act via a similar mechanism or pathway involving their RING finger domain but that their intrinsic activities and effects on endogenous and exogenous proteins differ in detail.
Parkinson
J
J
MRC Virology Unit, Glasgow G11 5JR, Scotland, United Kingdom. j.parkinson@vir.gla.ac.uk
Everett
R D
RD
D018138:Alphaherpesvirinae / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000378:metabolism; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D000939:Epitopes; D018259:Herpesvirus 1, Human / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D025842:SUMO-1 Protein; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D044767:Ubiquitin-Protein Ligases; D000076084:Ubiquitin-Specific Peptidase 7; D014452:Ubiquitins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
D034961:Antigens, Nuclear; D001324:Autoantigens; D000939:Epitopes; D017874:Immediate-Early Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D014764:Viral Proteins; C066642:SP100 protein, human; C070576:PML protein, human; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex