Document Detail

The products of the herpes simplex virus type 1 immediate-early US1/US1.5 genes downregulate levels of S-phase-specific cyclins and facilitate virus replication in S-phase Vero cells.
MedLine Citation:
PMID:  16571817     Owner:  NLM     Status:  MEDLINE    
Herpes simplex virus type 1 ICP22-/U(S)1.5- mutants initiate viral gene expression in all cells; however, in most cell types, the replication process stalls due to an inability to express gamma2 late proteins. Although the function of ICP22/U(S)1.5 has not been established, it has been suggested that these proteins activate, induce, or repress the activity of cellular proteins during infection. In this study, we hypothesized that cell cycle-associated proteins are targets of ICP22/U(S)1.5. For this purpose, we first isolated and characterized an ICP22-/U(S)1.5- mutant virus, 22/n199. Like other ICP22-/U(S)1.5- mutants, 22/n199 replicates in a cell-type-specific manner and fails to induce efficient gamma2 late gene expression in restrictive cells. Although synchronization of restrictive human embryonic lung cells in each phase of the cell cycle did not overcome the growth restrictions of 22/n199, synchronization of permissive Vero cells in S phase rendered them less able to support 22/n199 plaque formation and replication. Consistent with this finding, expression of cellular S-phase cyclins was altered in an ICP22/U(S)1.5-dependent manner specifically when S-phase Vero cells were infected. Collectively, these observations support the notion that ICP22/U(S)1.5 deregulates the cell cycle upon infection of S-phase permissive cells by altering expression of key cell cycle regulatory proteins either directly or indirectly.
Joseph S Orlando; Todd L Astor; Scott A Rundle; Priscilla A Schaffer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of virology     Volume:  80     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-30     Completed Date:  2006-04-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4005-16     Citation Subset:  IM    
Department of Medicine, Harvard Medical School at the Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN 123, Boston, Massachusetts 02215, USA.
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MeSH Terms
Cercopithecus aethiops
Cyclin E / physiology
Cyclin-Dependent Kinases / analysis
Cyclins / analysis*
Herpesvirus 1, Human / physiology*
Immediate-Early Proteins / physiology*
S Phase*
Vero Cells
Viral Regulatory and Accessory Proteins
Virus Replication*
Reg. No./Substance:
0/Cyclin E; 0/Cyclins; 0/ICP22 protein, human herpesvirus 1; 0/Immediate-Early Proteins; 0/Viral Regulatory and Accessory Proteins; EC Kinases

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