Infrequent HIV Infection of Circulating Monocytes during Antiretroviral Therapy
| Autor: | Nicolas Chomont, Marta Massanella, Jintanat Ananworanich, Wendy Bakeman, Jean-Pierre Routy, James L. K. Fletcher, Pasiri Sithinamsuwan, Nitiya Chomchey, Victor Valcour, Thep Chalermchai, Somporn Tipsuk |
|---|---|
| Přispěvatelé: | Global Health |
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Anti-HIV Agents CD14 Primary Cell Culture Immunology Population Human immunodeficiency virus (HIV) HIV Infections Biology medicine.disease_cause Microbiology Monocytes Immunophenotyping Flow cytometry Cohort Studies 03 medical and health sciences Antiretroviral Therapy Highly Active Virology medicine Humans education 030304 developmental biology 0303 health sciences education.field_of_study medicine.diagnostic_test 030306 microbiology Monocyte Middle Aged Viral Load Cell sorting Flow Cytometry Thailand Antiretroviral therapy CD4 Lymphocyte Count 3. Good health medicine.anatomical_structure Insect Science DNA Viral Cohort HIV-1 Pathogenesis and Immunity |
| Zdroj: | J Virol Journal of virology, 94(1). American Society for Microbiology |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Whereas human immunodeficiency virus (HIV) persists in tissue macrophages during antiretroviral therapy (ART), the role of circulating monocytes as HIV reservoirs remains controversial. Three magnetic bead selection methods and flow cytometry cell sorting were compared for their capacity to yield pure CD14(+) monocyte populations. Cell sorting by flow cytometry provided the purest population of monocytes (median CD4(+) T-cell contamination, 0.06%), and the levels of CD4(+) T-cell contamination were positively correlated with the levels of integrated HIV DNA in the monocyte populations. Using cell sorting by flow cytometry, we assessed longitudinally the infection of monocytes and other cell subsets in a cohort of 29 Thai HIV-infected individuals. Low levels of HIV DNA were detected in a minority of monocyte fractions obtained before and after 1 year of ART (27% and 33%, respectively), whereas HIV DNA was readily detected in CD4(+) T cells from all samples. Additional samples (2 to 5 years of ART) were obtained from 5 individuals in whom monocyte infection was previously detected. Whereas CD4(+) T cells were infected at high levels at all time points, monocyte infection was inconsistent and absent in at least one longitudinal sample from 4/5 individuals. Our results indicate that infection of monocytes is infrequent and highlight the importance of using flow cytometry cell sorting to minimize contamination by CD4(+) T cells. IMPORTANCE The role of circulating monocytes as persistent HIV reservoirs during ART is still controversial. Several studies have reported persistent infection of monocytes in virally suppressed individuals; however, others failed to detect HIV in this subset. These discrepancies are likely explained by the diversity of the methods used to isolate monocytes and to detect HIV infection. In this study, we show that only flow cytometry cell sorting yields a highly pure population of monocytes largely devoid of CD4 contaminants. Using this approach in a longitudinal cohort of HIV-infected individuals before and during ART, we demonstrate that HIV is rarely found in monocytes from untreated and treated HIV-infected individuals. This study highlights the importance of using methods that yield highly pure populations of cells as flow cytometry cell sorting to minimize and control for CD4(+) T-cell contamination. |
| Databáze: | OpenAIRE |
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