The Latent Human Immunodeficiency Virus (HIV) Reservoir Resides Primarily in CD32−CD4+ T Cells in Perinatally HIV-Infected Adolescents With Long-Term Virologic Suppression
| Autor: | Deborah Persaud, Allison L. Agwu, Lilly V. Siems, Ya Hui Chen, Adit Dhummakupt, Purvish Patel, Hao Zhang, Aleisha Collinson-Streng, Dolly Singh, Thuy Anderson |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine CD32 Adolescent Population Human immunodeficiency virus (HIV) HIV Infections medicine.disease_cause Flow cytometry Major Articles and Brief Reports Young Adult 03 medical and health sciences 0302 clinical medicine Acquired immunodeficiency syndrome (AIDS) medicine Humans Immunology and Allergy 030212 general & internal medicine Young adult Receptor education Acquired Immunodeficiency Syndrome education.field_of_study biology medicine.diagnostic_test Receptors IgG Provirus medicine.disease Virology Virus Latency 030104 developmental biology Infectious Diseases Anti-Retroviral Agents HIV-1 biology.protein Female |
| Zdroj: | The Journal of Infectious Diseases. 219:80-88 |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | BACKGROUND: High-level expression of the Fcγ receptor, CD32(hi), 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 CD32(hi)CD4(+) T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32(hi) 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 CD32(hi) cells. Exponential HIV replication occurred exclusively in CD32(−)CD4(+) T cells (mean change, 17.46 pg/mL; P = .04). Induced provirus in CD32(hi)CD4(+) 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. |
| Databáze: | OpenAIRE |
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