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Journal of Virology, June 2003, p. 6660-6665, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6660-6665.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Varicella-Zoster Virus Gene 66 Transcription and Translation in Latently Infected Human Ganglia

Randall J. Cohrs,1* Donald H. Gilden,1,2 Paul R. Kinchington,3 Esther Grinfeld,4 and Peter G. E. Kennedy4

Departments of Neurology,1 Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262,2 Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213,3 Department of Neurology, University of Glasgow, Glasgow G51 4TF, Scotland, United Kingdom4

Received 19 December 2002/ Accepted 24 March 2003

Latent infection with varicella-zoster virus (VZV) is characterized by restricted virus gene expression and the absence of virus production. Of the ~70 predicted VZV genes, only five (genes 4, 21, 29, 62, and 63) have been shown by multiple techniques to be transcribed during latency. IE62, the protein product of VZV gene 62, is the major immediate-early (IE) virus-encoded transactivator of viral gene transcription and plays a pivotal role in transactivating viral genes during lytic infection. The protein kinase (66-pk) encoded by VZV gene 66 phosphorylates IE62, resulting in cytoplasmic accumulation of IE62 that mitigates nuclear IE62-induced gene activation. Analysis of latently infected human trigeminal ganglia for 66-pk expression by reverse transcriptase-dependent nested PCR, including DNA sequence analysis, in situ hybridization, and immunohistochemistry, revealed VZV open reading frame 66 to be a previously unrecognized latently expressed virus gene and suggests that prevention of IE62 import to the nucleus by VZV 66-pk phosphorylation is one possible mechanism by which VZV latency is maintained.

* Corresponding author. Mailing address: Department of Neurology, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Mail Stop B182, Denver, CO 80262. Phone: (303) 315-8745. Fax: (303) 315-8720. E-mail: randall.cohrs{at}uchsc.edu.

Journal of Virology, June 2003, p. 6660-6665, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6660-6665.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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