Evidence map›Paper›PMID 26842468›Full record

ArticleJournal of virology2016

The Herpes Simplex Virus Latency-Associated Transcript 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.

Ruchi Srivastava, Xavier Dervillez, Arif A Khan, Aziz A Chentoufi, Sravya Chilukuri, Nora Shukr, Yasmin Fazli, Nicolas N Ong, Rasha E Afifi, Nelson Osorio and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Article
  5. Review
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  7. Review
  8. Genome-Wide B Cell, CD4Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  9. Review
  10. Article
  11. Article
  12. Upregulation of Multiple CD8Journal of immunology (Baltimore, Md. : 1950) · 2020
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 3 countries.

Ruchi SrivastavaLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Xavier DervillezLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Arif A KhanLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Aziz A ChentoufiLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Sravya ChilukuriLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Nora ShukrLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Yasmin FazliLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Nicolas N OngLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Rasha E AfifiLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Nelson OsorioLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Roger GeertsemaUniversity Laboratory Animal Resources, University of California Irvine, Irvine, California, USA.
Anthony B NesburnLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
Steven L WechslerLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.ORCID http://orcid.org/0000-0001-8509-5229
Lbachir BenMohamedLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA lbenmoha@uci.edu.
University of California, Irvine · US

Funding

Corneal HSV-1: LAT's Anti-Apoptosis Activity and LatencyR01EY013191 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2001 to 2013
$6.9M
Therapeutic Ocular HSV Vaccine in HLA Transgenic RabbitsR01EY019896 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2010 to 2025
$5.1M
Ocular Mucsoal Immunity Induced by HSV-1 LipopeptidesR01EY014900 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2003 to 2014
$3.1M
Mechanisms of CD8+ T Cell Dynamics in Recurrent Ocular Herpetic DiseaseR01EY026103 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2016 to 2019
$1.5M
Blockade of T-cell Co-Inhibitory Pathways & Immunotherapy to Prevent Ocular HerpeR01EY024618 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2014 to 2016
$1.2M
LAT-HVEM Interactions Effect HSV-1 Latency/ReactivationR21AI110902 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2015 to 2016
$425k
HSV-1 LAT miRNAs: Neurovirulence, reactivation, mechanismR56AI098985 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2013 to 2013
$421k
Corneal HSV-1: Newly discovered LAT miRNAs and latencyR56AI093133 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2011 to 2011
$383k
NEI NIH HHS EY013191NEI NIH HHS EY019896NEI NIH HHS EY024618NEI NIH HHS R01 EY013191NEI NIH HHS R01 EY014900NEI NIH HHS R01 EY019896NEI NIH HHS R01 EY024618NEI NIH HHS R01 EY026103NIAID NIH HHS 1R21AI110902NIAID NIH HHS 1R56AI093133NIAID NIH HHS 1R56AI098985NIAID NIH HHS R21 AI110902NIAID NIH HHS R56 AI093133NIAID NIH HHS R56 AI098985
6 · The paper itself

Abstract

unlabelledPersistent pathogens, such as herpes simplex virus 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 or with LAT-rescued mutant (i.e., LAT(+)TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT(-)TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8(+)T cells in LAT(+)TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8(+)T cells specific to 40 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(+)versus LAT(-)virus. Compared to CD8(+)T cells from LAT(-)TG, CD8(+)T cells from LAT(+)TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. 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 for increased viral reactivation. IMPORTANCE: A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8(+)T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT(+)TG) than in a more restricted repertoire of functional HSV-specific CD8(+)T cells in the TG of HLA transgenic rabbits latently infected with LAT-null mutant (i.e., LAT(-)TG). These findings suggest that the HSV-1 LAT locus interferes with the host cellular immune response by shaping a broader repertoire of exhausted HSV-specific CD8(+)T cells within the latency/reactivation TG site.

Indexed as

Virus LatencyAnimalsAnimals, Genetically ModifiedCD8-Positive T-LymphocytesEpitopes, T-LymphocyteGene ExpressionHerpesvirus 1, HumanHLA-A2 AntigenHumansImmune EvasionLymphocyte CountMicroRNAsRabbitsTrigeminal GanglionEpitopes, T-LymphocyteHLA-A*02:01 antigenHLA-A2 Antigenlatency associated transcript, herpes simplex virus-1MicroRNAs

Identifiers

PMID26842468
PMCPMC4810530
OpenAlexW2330376476

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.