HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies

Virology. 2014 Aug:462-463:175-88. doi: 10.1016/j.virol.2014.06.008. Epub 2014 Jul 4.

Abstract

Granzyme B (GrzB) is expressed by activated T cells and mediates cellular apoptosis. GrzB also acts as an extracellular protease involved in tissue degradation. We hypothesized that GrzB production from activated memory CD4 T cells may be associated with HIV pathogenesis. We found that stimulated memory CD4 T cells (via costimulation, cytokines, and TLR ligands) concomitantly produced GrzB and HIV. Both GrzB and HIV expression were mainly restricted to CCR5-expressing memory CD4+CD45RO+ T cells, including Th1 and Th17 subsets. Activated memory CD4 T cells also mediated tissue damage, such as disruption of intestinal epithelial monolayers. In non-human primates, CD4 T cells of rhesus macaques (pathogenic SIV hosts) expressed higher GrzB compared to African green monkeys (non-pathogenic SIV hosts). These results suggest that GrzB from CCR5+ memory CD4 T cells may have a role in cellular and tissue pathologies during HIV infection.

Keywords: CCR5; Enteropathy; Granzyme B; HIV replication; Memory CD4 T cells; SIV pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Granzymes / metabolism*
  • HIV / physiology*
  • Humans
  • Leukocyte Common Antigens / analysis
  • Macaca mulatta
  • Receptors, CCR5 / analysis*
  • Th1 Cells / metabolism
  • Th1 Cells / virology
  • Th17 Cells / metabolism
  • Th17 Cells / virology
  • Virus Replication*

Substances

  • CCR5 protein, human
  • Receptors, CCR5
  • Leukocyte Common Antigens
  • Granzymes