May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Phenotype and Function of Dendritic Cells Is Regulated by the Latency-Associated Transcript (LAT) Region of HSV-1
Author Affiliations & Notes
  • A.B. Nesburn
    Dept. Ophthalmology, University of California, Irvine, Orange, CA, United States
  • S.L. Wechsler
    Dept. Ophthalmology, University of California, Irvine, Orange, CA, United States
  • L. BenMohamed
    Dept. Ophthalmology, University of California, Irvine, Orange, CA, United States
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 717. doi:
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      A.B. Nesburn, S.L. Wechsler, L. BenMohamed; Phenotype and Function of Dendritic Cells Is Regulated by the Latency-Associated Transcript (LAT) Region of HSV-1 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):717.

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

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Abstract

Abstract: : Purpose: Herpes simplex viruses (HSV) establish a life-long latent infection in their human hosts. Diverse evasion strategies are used by HSV to inhibit, block, or evade the immune response. The strategic positioning of immature dendritic cells (DC) in mucosal tissues, including the ocular surface, makes them likely to be the primary HSV-1 antigen-presenting cells (APC). Immature DC expressing viral antigens must be activated to mature, before they can serve as APC. HSV-1 can infect DC and interfere with maturation. The stimuli and viral genes involved in this interference remain to be determined. Our goal was to investigate the role of the HSV-1 Latency Associated Transcript (LAT), the only viral gene abundantly transcribed during both acute and latent infection, on phenotype and function of DC. Methods: Murine bone marrow derived DC were infected in vitro with i) the LAT null mutant dLAT2903; ii) its marker rescued virus dLAT2903R or iii) the parental HSV-1 strain McKrae. The levels of expression of CD40, CD54, CD80, CD86 and MHC class I and class II molecules were measured by flow cytometry. These membrane molecules are all indicators of DC maturation. Results: DC infected with dLAT2903 virus expressed the highest level of viral proteins compared to DC infected with dLAT2903R or McKrae. In contrast, in CV-1 cells and RS cells, the level of viral proteins was similar with all viruses. Infection of immature DC with dLAT2903, but not with McKrae or dLAT2903R, led to significant, selective and asynchronous down-regulation of CD40, CD54, CD80, CD86, MHC class I and class II molecules. The uptake exogenous antigen by dLAT2903R and McKrae-infected DC, but not by dLAT2903-infected DC, was reduced, another characteristic feature of DC maturation. Consistent with these findings, infection of DC by dLAT2903, but not by the dLAT2903R or McKrae, strongly impaired their ability to stimulate allogeneic T cells. Conclusions: (1) In DC, LAT inhibited cell surface expression of viral antigens, which may delay T cell activation, allowing more time for replication of HSV-1. (2) The impairment of DC function by the product of LAT may represent a novel strategy employed by HSV for weakening in vivo the host's immune responses, likely to help confer a life-long latent infection.

Keywords: herpes simplex virus • immunomodulation/immunoregulation • flow cytometry 
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