September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The Herpes Simplex Virus LAT Gene is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits
Author Affiliations & Notes
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States
  • Arif Khan
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States
  • Ruchi Srivastava
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States
  • Steven Wechsler
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States
  • Anthony B Nesburn
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Lbachir BenMohamed, None; Arif Khan, None; Ruchi Srivastava, None; Steven Wechsler, None; Anthony Nesburn, None
  • Footnotes
    Support  EY14900, EY019896, EY024618, EY013191, The Discovery Eye Foundation, The Discovery Center for Eye Research, and a Research to Prevent Blindness Challenge grant.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3293. doi:
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      Lbachir BenMohamed, Arif Khan, Ruchi Srivastava, Steven Wechsler, Anthony B Nesburn; The Herpes Simplex Virus LAT Gene is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3293.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Persistent pathogens, such as herpes simplex virus type 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host’s immune system. A dynamic cross talk appears to occur between the HSV-1 Latency-Associated Transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8+ T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild type HSV-1 (i.e. LAT(+) TG) is significantly higher than TG latently infected with LAT null mutants (i.e. LAT(-) TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8+ T cells retained in LAT(+) TG is unknown.

Methods : In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8+ T cells specific to 40 different epitopes derived from HSV-1 gB, gD, VP11/12 and VP13/14 proteins, in Human Leukocyte Antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT(+) vs. LAT(-) virus.

Results : Compared to CD8+ T cells from LAT(-) TG, CD8+ T cells from LAT(+) TG: (i) recognized a broader selection of non-overlapping HSV-1 epitopes; (ii) expressed higher levels of PD-1, TIM-3 and CTLA-4, markers of exhaustion; and (iii) produced less TNF-a, IFN-g, and GzmB.

Conclusions : These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8+ T cells in latently infected TG, thus, allowing increased viral reactivation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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