The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32−CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term …
A Dhummakupt, LV Siems, D Singh… - The Journal of …, 2019 - academic.oup.com
A Dhummakupt, LV Siems, D Singh, YH Chen, T Anderson, A Collinson-Streng, H Zhang…
The Journal of infectious diseases, 2019•academic.oup.comBackground High-level expression of the Fcγ receptor, CD32hi, on CD4+ T cells was
associated with enhanced human immunodeficiency virus (HIV) infection of the latent
reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that
CD32 was the preferential marker of the latent HIV reservoir in virally suppressed,
perinatally HIV-infected adolescents. Methods The frequency of CD32hiCD4+ T cells was
determined by flow cytometry (N= 5) and the inducible HIV reservoir in both CD32hi and …
associated with enhanced human immunodeficiency virus (HIV) infection of the latent
reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that
CD32 was the preferential marker of the latent HIV reservoir in virally suppressed,
perinatally HIV-infected adolescents. Methods The frequency of CD32hiCD4+ T cells was
determined by flow cytometry (N= 5) and the inducible HIV reservoir in both CD32hi and …
Background
High-level expression of the Fcγ receptor, CD32hi, on CD4+ T cells was associated with enhanced human immunodeficiency virus (HIV) infection of the latent reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latent HIV reservoir in virally suppressed, perinatally HIV-infected adolescents.
Methods
The frequency of CD32hiCD4+ T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32hi and CD32−CD4+ T cells was quantified (N = 4) with a quantitative viral outgrowth assay. Viral outgrowth was measured by the standard p24 enzyme-linked immunosorbent assay and an ultrasensitive p24 assay (Simoa; Quanterix) with lower limits of quantitation.
Results
We found a 59.55-fold enrichment in the absolute number of infectious cells in the CD32− population compared with CD32hi cells. Exponential HIV replication occurred exclusively in CD32−CD4+ T cells (mean change, 17.46 pg/mL; P = .04). Induced provirus in CD32hiCD4+ T cells replicated to substantially lower levels, which did not increase significantly over time (mean change, 0.026 pg/mL; P = .23) and were detected only with the Simoa assay.
Conclusions
Our data suggests that the latent HIV reservoir resides mainly in CD32−CD4+ T cells in virally suppressed, perinatally HIV-infected adolescents, which has implications for reservoir elimination strategies.
Oxford University Press