Characterization of Elite Suppressors Cell-Associated HIV-1 mRNA at Baseline and with T Cell Activation

Yale J Biol Med. 2017 Jun 23;90(2):331-336. eCollection 2017 Jun.

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 HIV-mRNA levels released into culture supernatant. Results: ES have significantly less cell associated HIV-mRNA 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.

Keywords: Elite controllers; Elite suppressors; mRNA transcription; reservoirs.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / virology
  • DNA, Viral / analysis
  • Disease Progression
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV Long-Term Survivors*
  • HIV-1* / genetics
  • HIV-1* / physiology
  • Humans
  • RNA, Messenger / analysis*
  • RNA, Viral / analysis*

Substances

  • DNA, Viral
  • RNA, Messenger
  • RNA, Viral