Document Detail

Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency.
MedLine Citation:
PMID:  16352529     Owner:  NLM     Status:  MEDLINE    
The herpes simplex virus genome can enter a repressed transcriptional state (latency) in sensory neurons of the host nervous system. Although reduced permissiveness of the neuronal environment is widely accepted as a causal factor, the molecular pathway(s) directing and maintaining the viral genome in the latent state remains undefined. Over the past decade, the field has been strongly influenced by the observations of Kosz-Vnenchak et al., which have been interpreted to indicate that, in sensory neurons in vivo, a critical level of viral DNA synthesis within the neuron is required for sufficient viral immediate-early (IE) and early (E) gene expression (M. Kosz-Vnenchak, J. Jacobson, D. M. Coen, and D. M. Knipe, J. Virol. 67:5383-5393, 1993). The levels of IE and E genes are, in turn, thought to regulate the decision to enter the lytic cycle or latency. We have reexamined this issue using new strategies for in situ detection and quantification of viral gene expression in whole tissues. Our results using thymidine kinase-null and rescued mutants as well as wild-type strains in conjunction with viral DNA synthesis blockers demonstrate that (i) despite inhibition of viral DNA replication, many neurons express lytic viral proteins, including IE proteins, during acute infection in the ganglion; (ii) at early times postinoculation, the number of neurons expressing viral proteins in the ganglion is not reduced by inhibition of viral DNA replication; and (iii) following a reactivation stimulus, the numbers of neurons and apparent levels of lytic viral proteins, including IE proteins, are not reduced by inhibition of viral DNA replication. We conclude that viral DNA replication in the neuron per se does not regulate IE gene expression or entry into the lytic cycle.
N M Sawtell; R L Thompson; R L Haas
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of virology     Volume:  80     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-14     Completed Date:  2007-01-26     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38-50     Citation Subset:  IM    
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. Sawtn0@CHMCC.ORG
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MeSH Terms
Basic-Leucine Zipper Transcription Factors
DNA, Viral / biosynthesis,  physiology*
Gene Expression Regulation, Viral
Immediate-Early Proteins / genetics,  metabolism
Neurons / metabolism*,  virology
Peripheral Nervous System
Repressor Proteins
Simplexvirus / genetics,  metabolism,  physiology*
Trigeminal Ganglion / metabolism*,  pathology,  virology
Viral Proteins
Virus Latency / physiology*
Virus Replication
Grant Support
Reg. No./Substance:
0/Basic-Leucine Zipper Transcription Factors; 0/DNA, Viral; 0/Immediate-Early Proteins; 0/K8 protein, Human herpesvirus 8; 0/Repressor Proteins; 0/Viral Proteins

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