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 CNS. Here, we performed single-genome, near fu...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89837 |
| _version_ | 1797633631893585920 |
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| author | Weiwei Sun Yelizaveta Rassadkina Ce Gao Sarah Isabel Collens Xiaodong Lian Isaac H Solomon Shibani S Mukerji Xu G Yu Mathias Lichterfeld |
| author_facet | Weiwei Sun Yelizaveta Rassadkina Ce Gao Sarah Isabel Collens Xiaodong Lian Isaac H Solomon Shibani S Mukerji Xu G Yu Mathias Lichterfeld |
| author_sort | Weiwei Sun |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-03-11T11:56:37Z |
| format | Article |
| id | doaj.art-3fa3d723e3304b8e89a2f80d8618cef7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T11:56:37Z |
| publishDate | 2023-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3fa3d723e3304b8e89a2f80d8618cef72023-11-08T14:16:33ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.89837Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapyWeiwei Sun0https://orcid.org/0000-0002-4578-6292Yelizaveta Rassadkina1Ce Gao2Sarah Isabel Collens3Xiaodong Lian4Isaac H Solomon5Shibani S Mukerji6Xu G Yu7Mathias Lichterfeld8https://orcid.org/0000-0001-9865-8350Ragon Institute of MGH, MIT and Harvard, Cambridge, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United StatesDepartment of Neurology, Massachusetts General Hospital, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United StatesDepartment of Pathology, Brigham and Women’s Hospital, Boston, United StatesDepartment of Neurology, Massachusetts General Hospital, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United States; Infectious Disease Division, Brigham and Women’s Hospital, Boston, United StatesRagon Institute of MGH, MIT and Harvard, Cambridge, United States; Infectious Disease Division, Brigham and Women’s Hospital, Boston, United StatesHIV-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 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.https://elifesciences.org/articles/89837HIVreservoircentral nervous system |
| spellingShingle | Weiwei Sun Yelizaveta Rassadkina Ce Gao Sarah Isabel Collens Xiaodong Lian Isaac H Solomon Shibani S Mukerji Xu G Yu Mathias Lichterfeld Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy eLife HIV reservoir central nervous system |
| title | Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy |
| title_full | Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy |
| title_fullStr | Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy |
| title_full_unstemmed | Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy |
| title_short | Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy |
| title_sort | persistence of intact hiv 1 proviruses in the brain during antiretroviral therapy |
| topic | HIV reservoir central nervous system |
| url | https://elifesciences.org/articles/89837 |
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