HSV-1 IE protein Vmw110 causes redistribution of PML.
Herpes simplex virus immediate-early protein Vmw110 is required for fully efficient viral gene expression and reactivation from latency. At early times of viral infection, Vmw110 localizes to discrete nuclear structures (known as ND10, PODs or Kr bodies) which contain several cellular proteins, including PML. Interestingly, the unregulated growth of promyelocytic leukaemia cells is correlated with disruption of the normal state of ND10. In this paper we show that: (i) Vmw110 affects the distribution of PML in the cell; (ii) Vmw110 proteins lacking a functional RING finger zinc-binding domain cause the production of striking abnormal cytoplasmic and nuclear structures, some of which contain PML and other ND10 antigens; (iii) a mutant form of Vmw110 which is confined to the cytoplasm appears to result in cytoplasmic PML in some cells; (iv) normal interaction with the nuclear structures requires the C-terminal portion of Vmw110; (v) the C-terminal portion of Vmw110, when linked to a heterologous protein, disrupts the normal distribution of PML. The results suggest that, in normal cells, the PML protein migrates between nucleus and cytoplasm. These observations present an unexpected link between processes involved in the control of cell growth and viral infection and latency.
Medical Research Council Virology Unit, Institute of Virology, Glasgow, UK.
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Everett
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D000818:Animals; D034961:Antigens, Nuclear; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D018259:Herpesvirus 1, Human; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
D034961:Antigens, Nuclear; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1