Characterization of elite suppressors cell-associated HIV-1 mRNA at baseline and with T cell activation

Christopher W. Pohlmyer, C. Korin Bullen, Alyssa R. Martin, Gregory M. Laird, Stanley U. Chioma, Victoria E.K. Walker-Sperling, Joel N. Blankson

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Elite Controllers or Suppressors (ES†) are patients who control HIV replication without antiretroviral therapy. In this study, we compared baseline and inducible HIV-1 mRNA levels in CD4+ T cells from ES and chronic progressors (CPs) receiving suppressive antiretroviral therapy. Methods: We quantified basal levels of cell associated HIV-1 mRNA in CD4+ T cells isolated from CPs and ES. Additionally, we measured the fold upregulation of intracellular HIV-mRNA after stimulation of CD4+ T cells with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and quantified the amount of HIVmRNA levels released into culture supernatant. Results: ES have significantly less cell associated HIVmRNA per 5x106 cells (p = 0.003); 8 of 10 CPs had quantifiable HIV-1 mRNA at baseline, whereas this was present in only 2 of 10 ES. Upon stimulation with PMA and ionomycin, 4 of 5 CPs and 7 of 9 ES showed increased cell associated HIV-mRNA. Interestingly, released HIV-1 mRNA could be detected in supernatants of CD4+ T cells stimulated with PMA/ionomycin from 5 of 8 ES. Conclusion: Our results demonstrate that while the baseline levels of cell associated HIV-1 mRNA are significantly lower in ES compared to CPs, stimulation of CD4+ T cells results in a comparable relative upregulation of viral transcription.

Original languageEnglish (US)
Pages (from-to)331-336
Number of pages6
JournalYale Journal of Biology and Medicine
Volume90
Issue number2
StatePublished - Jun 2017

Keywords

  • Elite controllers
  • Elite suppressors
  • Reservoirs
  • mRNA transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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