April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Herpes Simplex Virus-1 Encoded Latency-Associated Transcript Promotes Dysfunctional Virus-Specific CD8+ T Cells in Latently Infected Trigeminal Ganglia: A Novel Immune Evasion Mechanism
Lbachir BenMohamed; Aziz A. Chentoufi; Michael V. Tran; Elizabeth Krizer; Rash E. Afifi; Nelson Osorio; Xianzhi Jiang; Dale Carpenter; Anthony B. Nesburn; Steven L. Wechsler
Author Affiliations & Notes
  • Lbachir BenMohamed
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
    Laboratory of Cellular and Molecular Immunology, University of California Irvine, School of Medicine, Irvine, Irvine, California
  • Aziz A. Chentoufi
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Michael V. Tran
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Elizabeth Krizer
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Rash E. Afifi
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Nelson Osorio
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Xianzhi Jiang
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Dale Carpenter
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Anthony B. Nesburn
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Steven L. Wechsler
    The Gavin Herbert Eye Institute, Univ of California-Irvine, Orange, California
  • Footnotes
    Commercial Relationships  Lbachir BenMohamed, None; Aziz A. Chentoufi, None; Michael V. Tran, None; Elizabeth Krizer, None; Rash E. Afifi, None; Nelson Osorio, None; Xianzhi Jiang, None; Dale Carpenter, None; Anthony B. Nesburn, None; Steven L. Wechsler, None
  • Footnotes
    Support  This work was supported by Public Health Service NIH grants to LBM EY14900 and EY019896, The Discovery Eye Foundation, The Henry L. Guenther Foundation, and Research to Prevent Blindness Challenge gra
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2909. doi:
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      Lbachir BenMohamed, Aziz A. Chentoufi, Michael V. Tran, Elizabeth Krizer, Rash E. Afifi, Nelson Osorio, Xianzhi Jiang, Dale Carpenter, Anthony B. Nesburn, Steven L. Wechsler; The Herpes Simplex Virus-1 Encoded Latency-Associated Transcript Promotes Dysfunctional Virus-Specific CD8+ T Cells in Latently Infected Trigeminal Ganglia: A Novel Immune Evasion Mechanism. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2909.

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Abstract

Purpose: : Following ocular herpes simplex virus type 1 (HSV-1) infection of mice, HSV-specific CD8+ T cells are induced and selectively retained in latently infected trigeminal ganglia (TG). Experimentally increasing the number of CD8 T-cells in the TG decreases reactivation of latent wild type HSV-1. We therefore hypothesized that increased numbers of HSV-1 specific functional CD8 T-cells in TG might be involved in the decreased reactivation of LAT(-) HSV-1 mutants.

Methods: : C57BL/6 mice were ocularly infected with LAT(+) or LAT(-) virus and the number and function of CD8 T-cells in TG were examined after latency was established (~35 days post infection). The viral genomic load in latently infected TG is ~2 fold higher with LAT(+) compared to LAT(-) viruses.

Results: : Although fewer total CD8 T-cells were found with LAT(-) virus, the LAT(-) TG had more functional HSV-1 specific CD8 T-cells, because most of the HSV-1 specific CD8 T-cells (HSV-gB498-505 tetramer+) from LAT(+) TG were exhausted (dysfunctional) as judged by high levels of PD1, impaired cytotoxicity, and decreased IFN-γ and TNF-α production. In addition, mouse neuroblastoma (Neuro2A) cells transfected with a LAT expressing plasmid, had elevated MHC-1 and PD-L1 compared to the same cells transfected with an empty plasmid and were resistant to lysis by allogeneic CD8+ T cells. Collectively, our findings suggest that TG from mice latently infected with LAT(-) virus had more HSV-1 specific functional CD8 T-cells than did TG from mice latently infected with LAT(+) virus. In addition, even in the absence of other HSV-1 gene products, LAT appeared to directly or indirectly up regulate PD-L1 and MHC-1.

Conclusions: : These findings may constitute a novel immune evasion mechanism whereby the HSV-1 LAT, directly or indirectly, promotes dysfunctional virus-specific CD8+ T cells in latently infected TG, which in turn directly or indirectly results in more virus reactivation compared to LAT(-) mutants.

Keywords: herpes simplex virus • immunomodulation/immunoregulation • inflammation 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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