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

精英抑制细胞相关 HIV-1 mRNA 的基线和 T 细胞活化特征

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

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.

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.

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.

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.

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