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Journal of Virology, January 2006, p. 38-50, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.38-50.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

N. M. Sawtell,1* R. L. Thompson,2 and R. L. Haas1

Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet Ave., Cincinnati, Ohio 45229-3039,1 University of Cincinnati Medical College, Department of Molecular Genetics, Biochemistry, and Microbiology, 231 Albert Sabin Way, Cincinnati, Ohio 45267-05242

Received 3 May 2005/ Accepted 16 September 2005

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Phone: (513) 636-7880. Fax: (513) 636-7655. E-mail: Sawtn0{at}CHMCC.ORG.

Journal of Virology, January 2006, p. 38-50, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.38-50.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thompson, R. L., Sawtell, N. M. (2006). Evidence that the Herpes Simplex Virus Type 1 ICP0 Protein Does Not Initiate Reactivation from Latency In Vivo. J. Virol. 80: 10919-10930 [Abstract] [Full Text]  


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