title: Herpes simplex virus induces extensive modification and dynamic relocalisation of the nuclear mitotic apparatus (NuMA) protein in interphase cells.
abstract: The nuclear mitotic apparatus (NuMA) protein is a component of the nuclear matrix in interphase cells and an essential protein for the formation of mitotic spindle poles. We used herpes simplex virus (HSV), an enveloped DNA virus that replicates in the nucleus, to study the intra-nuclear dynamics of NuMA in infected cells. This study shows that NuMA is extensively modified following HSV infection, including phosphorylation of an unidentified site(s), and that it depends to an extent on viral DNA synthesis. Although NuMA is insoluble in uninfected interphase cells, HSV infection induced solubilisation and dynamic relocalisation of NuMA, whereupon the protein became excluded from viral replication compartments -- sites of virus transcription and replication. Live cell, confocal imaging showed that NuMA localisation dramatically changed from the early stages (diffusely nuclear, excluding nucleoli) to late stages of infection (central diminuition, but remaining near the inner nuclear peripheries). In addition, NuMA knockdown using siRNA suggested that NuMA is important for efficient viral growth. In summary, we suggest that NuMA is required for efficient HSV infection, and identify further areas of research that address how the virus challenges host cell barriers.
authors.affiliation: Department of Virology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kiriyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis* / Q000648:ultrastructure; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006561:Herpes Simplex / Q000235:genetics* / Q000473:pathology; D018259:Herpesvirus 1, Human; D006801:Humans; D007399:Interphase / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D014162:Transfection; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D004279:DNA, Viral; D004791:Enzyme Inhibitors; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D034741:RNA, Small Interfering; D014764:Viral Proteins; D010770:Phosphotransferases; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus; D010746:Phosphonoacetic Acid