Differences in inducibility of the latent HIV reservoir in perinatal and adult infection
| Autor: | Adit Dhummakupt, Thuy Anderson, Allison L. Agwu, Jessica H. Rubens, Bareng A. S. Nonyane, Lilly V. Siems, R. Brad Jones, Deborah Persaud, Laura Powell, Tricia L. Nilles, Vicki Tepper, Aleisha Collinson-Streng |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes 0301 basic medicine Adolescent T cell Human immunodeficiency virus (HIV) HIV Infections Stimulation Virus Replication medicine.disease_cause Antiviral Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy Limiting dilution Humans Medicine Latency (engineering) Disease Reservoirs business.industry General Medicine Viral Load Virus Latency 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Ionomycin Immunology HIV-1 Female business Immunologic Memory Ex vivo Research Article Immune activation |
| Zdroj: | JCI Insight. 5 |
| ISSN: | 2379-3708 |
| Popis: | The HIV latent reservoir in resting memory CD4(+) T cells precludes cure. Therapeutics to reactivate and eliminate this reservoir are in clinical trials in adults, but not yet in pediatric populations. We determined, ex vivo, the inducibility of the latent reservoir in perinatal infection as compared with adult infections using the Tat/rev induced limiting dilution assay (TILDA), in which a single round (12 hours) of CD4(+) T cell stimulation with PMA/ionomycin maximally activates T cells and leads to proviral expression with multiply spliced HIV RNA production. Markers of immune activation and exhaustion were measured to assess interactions with inducibility. Although rates of T cell activation with PMA/ionomycin were similar, the latent reservoir in perinatal infection was slower to reactivate and of lower magnitude compared with adult infection, independent of proviral load. An enhanced TILDA with the addition of phytohemagglutin and a duration of 18 hours augmented proviral expression in perinatal but not adult infection. The baseline HLA-DR(+)CD4(+) T cell level was significantly lower in perinatal compared with adult infections, but not correlated with induced reservoir size. These data support the hypothesis that there are differences in kinetics of latency reversal and baseline immune activation in perinatal compared with adult infections, with implications for latency reversal strategies toward reservoir clearance and remission. |
| Databáze: | OpenAIRE |
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