Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response

Am J Pathol. 2003 Dec;163(6):2179-84. doi: 10.1016/S0002-9440(10)63575-4.

Abstract

The majority of trigeminal ganglia (TGs) are latently infected with alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very rarely. The goal of this study was to determine whether herpesvirus latency is linked to a local immune cell infiltration in human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42 examined TGs from 21 healthy individuals. The presence of immune cells correlated constantly with the occurrence of the HSV-1 latency-associated transcript (LAT) and only irregularly with the presence of latent VZV protein. In contrast, uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma, tumor necrosis factor-alpha, IP-10, and RANTES transcripts were significantly induced in TGs latently infected with HSV-1 but not in uninfected TGs. The persisting lymphocytic cell infiltration and the elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the first time that latent herpesviral infection in humans is accompanied by a chronic inflammatory process at an immunoprivileged site but without any neuronal destruction. The chronic immune response seems to maintain viral latency and influence viral reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Formation
  • Child
  • Child, Preschool
  • Computer Systems
  • Female
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / physiopathology
  • Herpesvirus 1, Human / physiology*
  • Herpesvirus 3, Human / physiology*
  • Humans
  • Immediate-Early Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Infant
  • Male
  • MicroRNAs
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Trans-Activators / metabolism
  • Trigeminal Ganglion / virology*
  • Viral Envelope Proteins / metabolism
  • Viral Proteins / metabolism
  • Virus Latency*

Substances

  • IE62 protein, Human herpesvirus 3
  • Immediate-Early Proteins
  • MicroRNAs
  • Trans-Activators
  • Viral Envelope Proteins
  • Viral Proteins
  • latency associated transcript, herpes simplex virus-1