Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent herpetic disease. After primary HSV-1 corneal infection, CD8+ T cells infiltrate the trigeminal ganglia (TGs) of mice, and are retained in latently infected ganglia. Here we demonstrate that CD8+ T cells that are present in the TGs at the time of excision can maintain HSV-1 in a latent state in sensory neurons in ex vivo TG cultures. Latently infected neurons expressed viral genome and some expressed HSV-1 immediate early and early proteins, but did not produce HSV-1 late proteins or infectious virions. Addition of anti-CD8α monoclonal antibody 5 d after culture initiation induced HSV-1 reactivation, as demonstrated by production of viral late proteins and infectious virions. Thus, CD8+ T cells can prevent HSV-1 reactivation without destroying the infected neurons. We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8+ T cells aborting virion production.
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1 May 2000
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April 24 2000
Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons
Ting Liu,
Ting Liu
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
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Kamal M. Khanna,
Kamal M. Khanna
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
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XiaoPing Chen,
XiaoPing Chen
bDepartment of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
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David J. Fink,
David J. Fink
bDepartment of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
cDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
dGeriatic Research Education Clinical Center and the Veterans Affairs Medical Center, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
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Robert L. Hendricks
Robert L. Hendricks
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
cDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
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Ting Liu
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
Kamal M. Khanna
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
XiaoPing Chen
bDepartment of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
David J. Fink
bDepartment of Neurology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
cDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
dGeriatic Research Education Clinical Center and the Veterans Affairs Medical Center, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
Robert L. Hendricks
aDepartment of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
cDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213
Abbreviations used in this paper: FISH, fluorescence in situ hybridization; gC, glycoprotein C; HPRT, hypoxanthineguanine phosphoribosyl transferase; HSV-1, HSV type 1; ICP, infected cell protein; IE, immediate early; RT, reverse transcription; TG, trigeminal ganglion.
Received:
October 28 1999
Revision Requested:
January 07 2000
Accepted:
February 10 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (9): 1459–1466.
Article history
Received:
October 28 1999
Revision Requested:
January 07 2000
Accepted:
February 10 2000
Citation
Ting Liu, Kamal M. Khanna, XiaoPing Chen, David J. Fink, Robert L. Hendricks; Cd8+ T Cells Can Block Herpes Simplex Virus Type 1 (HSV-1) Reactivation from Latency in Sensory Neurons. J Exp Med 1 May 2000; 191 (9): 1459–1466. doi: https://doi.org/10.1084/jem.191.9.1459
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