Details

Autor(en) / Beteiligte

• Dhummakupt, Adit
• Siems, Lilly V
• Singh, Dolly
• Chen, Ya Hui
• Anderson, Thuy
• Collinson-Streng, Aleisha
• Zhang, Hao
• Patel, Purvish
• Agwu, Allison
• Persaud, Deborah

Titel

The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32−CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term Virologic Suppression

Ist Teil von

• The Journal of infectious diseases, 2019-01, Vol.219 (1), p.80-88

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract 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. The infectious latent human immunodeficiency virus (HIV) reservoir resides predominantly in CD32−CD4+ T cells in perinatally HIV-infected adolescents. Using ultrasensitive p24 methods, inducible virus was detected in CD32hiCD4+ T-cell cocultures, with limited outgrowth. This has implications for reservoir elimination strategies.