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Journal of Virology, November 2001, p. 11178-11184, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11178-11184.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gamma Interferon Can Prevent Herpes Simplex Virus Type 1 Reactivation from Latency in Sensory Neurons

Ting Liu,1 Kamal M. Khanna,2 Brian N. Carriere,1 and Robert L. Hendricks1,3,*

Departments of Ophthalmology1 Molecular Genetics and Biochemistry,3 and Graduate Program in Immunology,2 School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Received 1 June 2001/Accepted 21 August 2001

We recently demonstrated that CD8+ T cells could block herpes simplex virus type 1 (HSV-1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying the infected neurons. Here we establish that CD8+ T-cell prevention of HSV-1 reactivation from latency is mediated at least in part by gamma interferon (IFN-gamma ). We demonstrate that IFN-gamma was produced in ex vivo cultures of dissociated latently infected TG by CD8+ T cells that were present in the TG at the time of excision. Depletion of CD8+ T cells or neutralization of IFN-gamma significantly enhanced the rate of HSV-1 reactivation from latency in TG cultures. When TG cultures were treated with acyclovir for 4 days to insure uniform latency, supplementation with recombinant IFN-gamma blocked HSV-1 reactivation in 80% of cultures when endogenous CD8+ T cells were present and significantly reduced and delayed HSV-1 reactivation when CD8+ T cells or CD45+ cells were depleted from the TG cultures. The effectiveness of recombinant IFN-gamma in blocking HSV-1 reactivation was lost when its addition to TG cultures was delayed by more than 24 h after acyclovir removal. We propose that when the intrinsic ability of neurons to inhibit HSV-1 gene expression is compromised, HSV-specific CD8+ T cells are rapidly mobilized to produce IFN-gamma and perhaps other antiviral cytokines that block the viral replication cycle and maintain the viral genome in a latent state.

* Corresponding author. Mailing address: University of Pittsburgh School of Medicine, Eye and Ear Institute, 203 Lothrop St., Pittsburgh, PA 15213-2588. Phone: (412) 647-5754. Fax: (412) 647-5880. E-mail: hendricksrr{at}msx.upmc.edu.

Journal of Virology, November 2001, p. 11178-11184, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11178-11184.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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