Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people
Abstract Characterizing the HIV-1 reservoir in blood and tissues is crucial for the development of curative strategies. Using an HIV Tat mRNA-containing lipid nanoparticle (Tat-LNP) in combination with panobinostat, we show that p24+ cells from blood and lymph nodes exhibit distinct phenotypes. Bloo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57332-5 |
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| _version_ | 1849761496361336832 |
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| author | Marion Pardons Laurens Lambrechts Ytse Noppe Liesbet Termote Sofie De Braekeleer Jerel Vega Ellen Van Gulck Sarah Gerlo Linos Vandekerckhove |
| author_facet | Marion Pardons Laurens Lambrechts Ytse Noppe Liesbet Termote Sofie De Braekeleer Jerel Vega Ellen Van Gulck Sarah Gerlo Linos Vandekerckhove |
| author_sort | Marion Pardons |
| collection | DOAJ |
| description | Abstract Characterizing the HIV-1 reservoir in blood and tissues is crucial for the development of curative strategies. Using an HIV Tat mRNA-containing lipid nanoparticle (Tat-LNP) in combination with panobinostat, we show that p24+ cells from blood and lymph nodes exhibit distinct phenotypes. Blood p24+ cells are found in both central/transitional (TCM/TTM) and effector memory subsets, mostly lack CXCR5 expression and are enriched in GZMA+ cells. In contrast, most lymph node p24+ cells display a TCM/TTM phenotype, with approximately 50% expressing CXCR5 and nearly all lacking GZMA expression. Furthermore, germinal center T follicular helper cells do not appear to harbor the translation-competent reservoir in long-term suppressed individuals. Near full-length HIV-1 sequencing in longitudinal samples from matched blood, lymph nodes, and gut indicates that clones of infected cells, including those carrying an inducible provirus, persist and spread across various anatomical compartments. Finally, uniform genetic diversity across sites suggests the absence of ongoing replication in tissues under treatment. |
| format | Article |
| id | doaj-art-de956f0b8d4643f79288771b5eb35e00 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-de956f0b8d4643f79288771b5eb35e002025-08-20T03:06:01ZengNature PortfolioNature Communications2041-17232025-03-0116111510.1038/s41467-025-57332-5Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed peopleMarion Pardons0Laurens Lambrechts1Ytse Noppe2Liesbet Termote3Sofie De Braekeleer4Jerel Vega5Ellen Van Gulck6Sarah Gerlo7Linos Vandekerckhove8HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityArcturus Therapeutics, 10628 Science Center Drive, Suite 250, San DiegoJohnson & Johnson Innovative Medicine, Janssen Pharmaceutica NVHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent UniversityAbstract Characterizing the HIV-1 reservoir in blood and tissues is crucial for the development of curative strategies. Using an HIV Tat mRNA-containing lipid nanoparticle (Tat-LNP) in combination with panobinostat, we show that p24+ cells from blood and lymph nodes exhibit distinct phenotypes. Blood p24+ cells are found in both central/transitional (TCM/TTM) and effector memory subsets, mostly lack CXCR5 expression and are enriched in GZMA+ cells. In contrast, most lymph node p24+ cells display a TCM/TTM phenotype, with approximately 50% expressing CXCR5 and nearly all lacking GZMA expression. Furthermore, germinal center T follicular helper cells do not appear to harbor the translation-competent reservoir in long-term suppressed individuals. Near full-length HIV-1 sequencing in longitudinal samples from matched blood, lymph nodes, and gut indicates that clones of infected cells, including those carrying an inducible provirus, persist and spread across various anatomical compartments. Finally, uniform genetic diversity across sites suggests the absence of ongoing replication in tissues under treatment.https://doi.org/10.1038/s41467-025-57332-5 |
| spellingShingle | Marion Pardons Laurens Lambrechts Ytse Noppe Liesbet Termote Sofie De Braekeleer Jerel Vega Ellen Van Gulck Sarah Gerlo Linos Vandekerckhove Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people Nature Communications |
| title | Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| title_full | Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| title_fullStr | Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| title_full_unstemmed | Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| title_short | Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| title_sort | blood and tissue hiv 1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people |
| url | https://doi.org/10.1038/s41467-025-57332-5 |
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