CD8(+) T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection

Immunol Cell Biol. 2008 Nov-Dec;86(8):666-75. doi: 10.1038/icb.2008.47. Epub 2008 Jul 8.

Abstract

During an initial encounter with herpes simplex virus type 1 (HSV-1) it takes several days for an adaptive immune response to develop and for herpes-specific CD8(+) T cells to infiltrate sites of infection. By this time the virus has firmly established itself within the innervating sensory nervous system where it then persists indefinitely. Preventing the establishment of viral latency would require blocking the skin to nervous system transmission of the virus. We wished to examine if CD8(+) T cells present early during acute HSV-1 infection could block this transmission. We show that effector CD8(+) T cells failed to prevent the establishment of HSV latency even when present prior to infection. This lack of blocking likely reflects the delayed infiltration of the CD8(+) T cells into the infected skin. Examination of the kinetics of HSV-1 infection highlighted the rapidity at which the virus infects the sensory ganglia and singled out early viral replication within the skin as an important factor in determining the magnitude of the ensuing latent infection. Though unable to prevent the establishment of latency, CD8(+) T cells could reduce the average viral copy number of the residual latent infection by dampening the skin infection and thus limiting the skin-to-nerve transmission of virus.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / virology
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Skin / immunology*
  • Skin / innervation
  • Skin / virology
  • Viral Load
  • Virus Latency*
  • Virus Replication