Characterization of the immune response in ganglia after primary simian varicella virus infection

J Neurovirol. 2016 Jun;22(3):376-88. doi: 10.1007/s13365-015-0408-1. Epub 2015 Dec 16.

Abstract

Primary simian varicella virus (SVV) infection in non-human primates causes varicella, after which the virus becomes latent in ganglionic neurons and reactivates to cause zoster. The host response in ganglia during establishment of latency is ill-defined. Ganglia from five African green monkeys (AGMs) obtained at 9, 13, and 20 days post-intratracheal SVV inoculation (dpi) were analyzed by ex vivo flow cytometry, immunohistochemistry, and in situ hybridization. Ganglia at 13 and 20 dpi exhibited mild inflammation. Immune infiltrates consisted mostly of CD8(dim) and CD8(bright) memory T cells, some of which expressed granzyme B, and fewer CD11c(+) and CD68(+) cells. Chemoattractant CXCL10 transcripts were expressed in neurons and infiltrating inflammatory cells but did not co-localize with SVV open reading frame 63 (ORF63) RNA expression. Satellite glial cells expressed increased levels of activation markers CD68 and MHC class II at 13 and 20 dpi compared to those at 9 dpi. Overall, local immune responses emerged as viral DNA load in ganglia declined, suggesting that intra-ganglionic immunity contributes to restricting SVV replication.

Keywords: Immune response; Primary infection; Sensory ganglia; Simian varicella virus; Varicella-zoster virus.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Chlorocebus aethiops
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Ganglia, Sensory / immunology*
  • Ganglia, Sensory / virology
  • Gene Expression Regulation / immunology
  • Granzymes / genetics
  • Granzymes / immunology
  • Herpesvirus 3, Human / immunology*
  • Herpesvirus 3, Human / pathogenicity
  • Host-Pathogen Interactions
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / immunology
  • Immunologic Memory
  • Primate Diseases / genetics
  • Primate Diseases / immunology*
  • Primate Diseases / pathology
  • Sensory Receptor Cells / immunology*
  • Sensory Receptor Cells / virology
  • Varicella Zoster Virus Infection / genetics
  • Varicella Zoster Virus Infection / immunology
  • Varicella Zoster Virus Infection / pathology
  • Varicella Zoster Virus Infection / veterinary*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Load / genetics
  • Viral Load / immunology
  • Virus Activation*
  • Virus Latency*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD11c Antigen
  • CD68 antigen, human
  • Chemokine CXCL10
  • DNA, Viral
  • Immediate-Early Proteins
  • Viral Envelope Proteins
  • immediate early protein 63, Human herpesvirus 3
  • Granzymes