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Title: Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity

Abstract

Studies of human cytomegalovirus (HCMV) UL97 kinase deletion mutant ({delta}UL97) indicated a multi-step role for this kinase in early and late phases of the viral life cycle, namely, in DNA replication, capsid maturation and nuclear egress. Here, we addressed its possible involvement in cytoplasmic steps of HCMV assembly. Using the {delta}UL97 and the UL97 kinase inhibitor NGIC-I, we demonstrate that the absence of UL97 kinase activity results in a modified subcellular distribution of the viral structural protein assembly sites, from compact structures impacting upon the nucleus to diffuse perinuclear structures punctuated by large vacuoles. Infection by either wild type or {delta}UL97 viruses induced a profound reorganization of wheat germ agglutinin (WGA)-positive Golgi-related structures. Importantly, the viral-induced Golgi remodeling along with the reorganization of the nuclear architecture was substantially altered in the absence of UL97 kinase activity. These findings suggest that UL97 kinase activity might contribute to organization of the viral cytoplasmic assembly sites.

Authors:
 [1];  [2];  [3];  [4];  [4];  [5]
  1. Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, 91120 (Israel)
  2. (Israel)
  3. Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem (Israel)
  4. Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem (Israel)
  5. Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, 91120 (Israel). E-mail: wolfd@md.huji.ac.il
Publication Date:
OSTI Identifier:
20850571
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 354; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2006.05.037; PII: S0042-6822(06)00369-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGGLUTININS; DNA REPLICATION; LIFE CYCLE; MUTANTS; PROTEINS; SUBCELLULAR DISTRIBUTION; VIRUSES; WHEAT

Citation Formats

Azzeh, Maysa, Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Honigman, Alik, Taraboulos, Albert, Rouvinski, Alexander, and Wolf, Dana G. Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity. United States: N. p., 2006. Web. doi:10.1016/j.virol.2006.05.037.
Azzeh, Maysa, Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Honigman, Alik, Taraboulos, Albert, Rouvinski, Alexander, & Wolf, Dana G. Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity. United States. doi:10.1016/j.virol.2006.05.037.
Azzeh, Maysa, Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Honigman, Alik, Taraboulos, Albert, Rouvinski, Alexander, and Wolf, Dana G. Tue . "Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity". United States. doi:10.1016/j.virol.2006.05.037.
@article{osti_20850571,
title = {Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity},
author = {Azzeh, Maysa and Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem and Honigman, Alik and Taraboulos, Albert and Rouvinski, Alexander and Wolf, Dana G.},
abstractNote = {Studies of human cytomegalovirus (HCMV) UL97 kinase deletion mutant ({delta}UL97) indicated a multi-step role for this kinase in early and late phases of the viral life cycle, namely, in DNA replication, capsid maturation and nuclear egress. Here, we addressed its possible involvement in cytoplasmic steps of HCMV assembly. Using the {delta}UL97 and the UL97 kinase inhibitor NGIC-I, we demonstrate that the absence of UL97 kinase activity results in a modified subcellular distribution of the viral structural protein assembly sites, from compact structures impacting upon the nucleus to diffuse perinuclear structures punctuated by large vacuoles. Infection by either wild type or {delta}UL97 viruses induced a profound reorganization of wheat germ agglutinin (WGA)-positive Golgi-related structures. Importantly, the viral-induced Golgi remodeling along with the reorganization of the nuclear architecture was substantially altered in the absence of UL97 kinase activity. These findings suggest that UL97 kinase activity might contribute to organization of the viral cytoplasmic assembly sites.},
doi = {10.1016/j.virol.2006.05.037},
journal = {Virology},
issn = {0042-6822},
number = 1,
volume = 354,
place = {United States},
year = {2006},
month = {10}
}