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 journalArticle

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 1 2017

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HIV-1
T-Lymphocytes
Messenger RNA
T-cells
Ionomycin
Myristic Acid
Acetates
HIV
Up-Regulation
Cape Verde
Electroretinography
Blood Flow Velocity
Transcription

Keywords

  • Elite controllers
  • Elite suppressors
  • mRNA transcription
  • Reservoirs

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pohlmyer, C. W., Bullen, C. K., Martin, A. R., Laird, G. M., Chioma, S. U., Walker-Sperling, V. E. K., & Blankson, J. N. (2017). Characterization of elite suppressors cell-associated HIV-1 mRNA at baseline and with T cell activation. Yale Journal of Biology and Medicine, 90(2), 331-336.

Characterization of elite suppressors cell-associated HIV-1 mRNA at baseline and with T cell activation. / Pohlmyer, Christopher W.; Bullen, C. Korin; Martin, Alyssa R.; Laird, Gregory M.; Chioma, Stanley U.; Walker-Sperling, Victoria E.K.; Blankson, Joel N.

In: Yale Journal of Biology and Medicine, Vol. 90, No. 2, 01.06.2017, p. 331-336.

Research output: Contribution to journalArticle

Pohlmyer CW, Bullen CK, Martin AR, Laird GM, Chioma SU, Walker-Sperling VEK et al. Characterization of elite suppressors cell-associated HIV-1 mRNA at baseline and with T cell activation. Yale Journal of Biology and Medicine. 2017 Jun 1;90(2):331-336.

Pohlmyer, Christopher W.; Bullen, C. Korin; Martin, Alyssa R.; Laird, Gregory M.; Chioma, Stanley U.; Walker-Sperling, Victoria E.K.; Blankson, Joel N. / Characterization of elite suppressors cell-associated HIV-1 mRNA at baseline and with T cell activation.

In: Yale Journal of Biology and Medicine, Vol. 90, No. 2, 01.06.2017, p. 331-336.

Research output: Contribution to journalArticle

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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.",
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