March 2012
Volume 53, Issue 14
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ARVO Annual Meeting Abstract  |   March 2012
The Herpes Simplex Virus Type 1 Latency Associated Transcript Inhibits Phenotypic and Functional Maturation of Dendritic Cells
Author Affiliations & Notes
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Aziz A. Chentoufi
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Xavier Dervillez
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Gargi Dasgupta
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Chelsea Nguyen
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Khaled K. Kabbara
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Steven L. Wechsler
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Anthony B. Nesburn
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, California
  • Footnotes
    Commercial Relationships  Lbachir BenMohamed, None; Aziz A. Chentoufi, None; Xavier Dervillez, None; Gargi Dasgupta, None; Chelsea Nguyen, None; Khaled K. Kabbara, None; Steven L. Wechsler, None; Anthony B. Nesburn, None
  • Footnotes
    Support  NIH NEI grants EY019896, EY14900, EY14017 from the NIH, by the Discovery Eye Foundation and an unrestricted grant from Research to Prevent Blindness. L.B.M. is an RPB Special Award Investigator.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6147. doi:
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      Lbachir BenMohamed, Aziz A. Chentoufi, Xavier Dervillez, Gargi Dasgupta, Chelsea Nguyen, Khaled K. Kabbara, Steven L. Wechsler, Anthony B. Nesburn; The Herpes Simplex Virus Type 1 Latency Associated Transcript Inhibits Phenotypic and Functional Maturation of Dendritic Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6147.

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Abstract

Purpose: : The maturation status of dendritic cells (DC) determines whether they prime or tolerize T cells. We recently found that the herpes simplex virus-1 (HSV-1) latency-associated transcript (LAT) results in exhaustion of virus-specific CD8+ T cells in latently infected trigeminal ganglia (TG). In this study we sought to determine if this impairment might involve LAT interfering with DC maturation.

Methods: : Phenotypic and functional maturation of bone marrow derived DC was studied in vitro. The presence of HSV-Ag positive DCs were investigated in the TG of latently infected latently infected CD11c/eYFP mice.

Results: : We found that HSV-1 antigen positive DC were present in the TG of latently infected CD11c/eYFP mice. In addition, some CD8+ T cells were adjacent to DCs, suggesting possible interactions. It has previously been shown that wild type HSV-1 interferes with DC maturation. Here, we show for the first time that this is associated with LAT expression, since, compared to LAT(-) virus: (i) LAT(+) virus interfered with DC surface expression of MHC class I and the co-stimulatory molecules CD80 and CD86; (ii) LAT(+) virus impaired DC production of IL-6, IL-12 and TNF-α pro-inflammatory cytokines; and (iii) DC infected with LAT(+) virus had significantly reduced antigen presentation ability to stimulate HSV-specific CD8+ T cells. While a similar number of CD11c+ DC was found in LAT(+) and LAT(-) latently infected TG of CD11c/eYFP transgenic mice, more HSV-1 Ag positive DC and more exhausted CD8 T cells were seen with LAT(+) virus. Consistent with these findings, HSV-specific cytotoxic CD8+ T cells in TG of mice latently infected with LAT(+) virus produced less IFN-γ and TNF-α than those from TG of LAT(-) infected mice.

Conclusions: : Together, these results suggest a novel immune-evasion mechanism whereby the HSV-1 LAT both increases the number of HSV-1 Ag positive DC in latently infected TG and interferes with DC phenotypic and functional maturation. The effect of LAT on TG-resident DC may contribute to the high proportion of exhausted HSV-specific CD8+ T-cell in TG of mice latently infected with LAT(+) virus.

Keywords: herpes simplex virus • inflammation • immunomodulation/immunoregulation 
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