Epitopes described in "The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1."

Article Authors:Sariah J Allen; Pedram Hamrah; David Gate; Kevin R Mott; Dimosthenis Mantopoulos; Lixin Zheng; Terrence Town; Clinton Jones; Ulrich H von Andrian; Gordon J Freeman; Arlene H Sharpe; Lbachir BenMohamed; Rafi Ahmed; Steven L Wechsler; Homayon Ghiasi
Article Title:The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1.
Reference Detail
Reference ID:1022017
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-). 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.
Affiliations:Center for Neurobiology and Vaccine Development, D2024, Cedars-Sinai Burns and Allen Research Institute, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Reference Type:Literature
PubMed ID:21307196
Journal:J Virol
Journal Volume:85
Article Pages:4184-97
Journal ISSN:1098-5514
Article Chemical List:Antigens, CD8;Antigens, Differentiation;Havcr2 protein, mouse;MicroRNAs;Pdcd1 protein, mouse;Programmed Cell Death 1 Receptor;Receptors, Virus;latency associated transcript, herpes simplex virus-1
Article MeSH List:Animals; Antigens, CD8(biosynthesis); Antigens, Differentiation(biosynthesis); CD8-Positive T-Lymphocytes(immunology); Flow Cytometry; Gene Expression Profiling; Herpes Simplex(immunology; virology); Herpesvirus 1, Human(immunology); Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; MicroRNAs(metabolism); Programmed Cell Death 1 Receptor; Receptors, Virus(biosynthesis); Trigeminal Ganglion(immunology); Virus Latency
Curation Last Updated:2015-07-30 20:39:29