Document Detail


UL74 of human cytomegalovirus contributes to virus release by promoting secondary envelopment of virions.
MedLine Citation:
PMID:  18184717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The glycoprotein (g) complex gH/gL represents an essential part of the herpesvirus fusion machinery mediating entry of cell-free virions and cell-associated viral spread. In some herpesviruses additional proteins are associated with gH/gL contributing to the cell tropism of the respective virus. Human cytomegalovirus (HCMV) gH/gL forms complexes with either gO (UL74) or proteins of the UL128-131A gene locus. While a contribution of UL128-131A to endothelial cell tropism is known, the role of gO is less clear. We studied the role of gH/gL-associated proteins in HCMV replication in human foreskin fibroblasts (HFF) and human umbilical vein endothelial cells (HUVEC). Deletions of UL74 alone or in combination with mutations of the UL128-131A gene region were introduced into bacterial artificial chromosome vectors derived from the endotheliotropic strain TB40/E. Deletion of UL74 caused a profound defect regarding virus release from infected HFF and HUVEC. Large numbers of capsids accumulated in the cytoplasm of infected HFF but failed to acquire an envelope. Clear cell type differences were observed in the cell-associated spread of the UL74-defective virus. In HFF, focal growth was severely impaired, whereas it was normal in HUVEC. Deletion of UL131A abolished focal growth in endothelial cells. UL74/UL128-131A dual mutants showed severely impaired reconstitution efficiency. Our data suggest that gO plays a critical role in secondary envelopment and release of cell-free virions independent of the cell type but affects cell-associated growth specifically in HFF, whereas UL128-131A contributes to cell-associated spread in HFF and HUVEC.
Authors:
Xiao Jing Jiang; Barbara Adler; Kerstin Laib Sampaio; Margarete Digel; Gerhard Jahn; Nicole Ettischer; York-Dieter Stierhof; Laura Scrivano; Ulrich Koszinowski; Michael Mach; Christian Sinzger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-09
Journal Detail:
Title:  Journal of virology     Volume:  82     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-26     Completed Date:  2008-03-31     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2802-12     Citation Subset:  IM    
Affiliation:
Institut für Medizinische Virologie, Eberhard Karls Universität, Tübingen, Elfriede Aulhorn Strasse 6, D-72076 Tübingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Chromosomes, Artificial, Bacterial
Cytomegalovirus / physiology*
Fibroblasts / cytology,  metabolism
Humans
Kinetics
Membrane Glycoproteins / physiology*
Microscopy, Electron
Microscopy, Fluorescence
Mutagenesis
Open Reading Frames
Viral Envelope Proteins / physiology*
Virion / physiology*
Virus Replication
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Viral Envelope Proteins; 0/glycoprotein O, cytomegalovirus
Comments/Corrections

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