Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy
HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the central nervous system (CNS). Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2023) vom: 14. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Weiwei [VerfasserIn] |
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| Anmerkungen: |
Date Revised 11.02.2024 published: Electronic UpdateIn: Elife. 2023 Nov 08;12:. - PMID 37938115 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2023.06.26.546135 |
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| funding: |
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| PPN (Katalog-ID): |
NLM359268900 |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the central nervous system (CNS). Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies | ||
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| 700 | 1 | |a Collens, Sarah Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Solomon, Isaac H |e verfasserin |4 aut | |
| 700 | 1 | |a Mukerji, Shibani |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xu G |e verfasserin |4 aut | |
| 700 | 1 | |a Lichterfeld, Mathias |e verfasserin |4 aut | |
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