ArticleJournal of virology2011
The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 124 citations in OpenAlex.
- HSV-1 LAT promotes ocular diseases in the absence of type I IFN responses in sensory neurons.Journal of virology · 2026Article
- Partial or complete blocking of gD binding to HVEM affects primary and latent HSV-1 infection as well as eye disease in HSV-1 infected mice.PLoS pathogens · 2026Article
- In the Absence of Type-1 IFN, HSV-1 LAT Increases γ34.5 Expression and Enhances Mortality in Infected Mice.Viruses · 2025Article
- IFNβ absence compensates for LAT functions in latency reactivation and T cell exhaustion.Journal of virology · 2025Article
- Immunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach.Viruses · 2025Review
- The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice.PLoS pathogens · 2024Article
- A Journey through the Minefield of the Discovery and Characterization of Latency-Related RNA/Latency-Associated Transcript.Viruses · 2024Review
- The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis.Clinical microbiology reviews · 2024Review
- The anti-apoptotic function of HSV-1 LAT in neuronal cell cultures but not its function during reactivation correlates with expression of two small non-coding RNAs, sncRNA1&2.PLoS pathogens · 2024Article
- Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3, but not the antibiotic Mithramycin A, stimulates human alphaherpesvirus 1 (HSV-1) replication.Antiviral research · 2024Article
- Absence of CD80 reduces HSV-1 replication in the eye and delays reactivation but not latency levels.Journal of virology · 2024Article
- High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4Frontiers in immunology · 2024Article
- Binding of herpesvirus entry mediator (HVEM) and HSV-1 gD affect reactivation but not latency levels.PLoS pathogens · 2023Article
- Immune Profiling Reveals Decreases in Circulating Regulatory and Exhausted T Cells in Human Hypertension.JACC. Basic to translational science · 2023Article
- Blocking Autophagy in M1 Macrophages Enhances Virus Replication and Eye Disease in Ocularly Infected Transgenic Mice.Journal of virology · 2022Article
- Understanding polyomavirus CNS disease - a perspective from mouse models.The FEBS journal · 2022Review
- Knockout of signal peptide peptidase in the eye reduces HSV-1 replication and eye disease in ocularly infected mice.PLoS pathogens · 2022Article
- Herpes Simplex Virus Type 1 Preferentially Enhances Neuro-Inflammation and Senescence in Brainstem of Female Mice.Journal of virology · 2022Article
- Small Noncoding RNA (sncRNA1) within the Latency-Associated Transcript Modulates Herpes Simplex Virus 1 Virulence and the Host Immune Response during Acute but Not Latent Infection.Journal of virology · 2022Article
- Herpes Simplex Virus 1 Small Noncoding RNAs 1 and 2 Activate the Herpesvirus Entry Mediator Promoter.Journal of virology · 2022Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(-)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(-) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8(+) T cells and more CD8(+) T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8(+) T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB(498-505)]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8(+) T cell exhaustion and latency in HSV-1 infection.
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Registered trials
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.