Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era
Summary: HIV-associated neurological compromise is observed in more than half of all people with HIV (PWH), even under antiretroviral therapy (ART). The mechanism has been associated with the early transmigration of HIV-infected monocytes across the BBB in a CCL2 and HIV replication-dependent manner...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224004577 |
| _version_ | 1827323188008189952 |
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| author | Cristian Hernandez Anna Maria Gorska Eliseo Eugenin |
| author_facet | Cristian Hernandez Anna Maria Gorska Eliseo Eugenin |
| author_sort | Cristian Hernandez |
| collection | DOAJ |
| description | Summary: HIV-associated neurological compromise is observed in more than half of all people with HIV (PWH), even under antiretroviral therapy (ART). The mechanism has been associated with the early transmigration of HIV-infected monocytes across the BBB in a CCL2 and HIV replication-dependent manner. However, the mechanisms of chronic brain damage are unknown.We demonstrate that all PWH under ART have elevated circulating ATP levels that correlate with the onset of cognitive impairment even in the absence of a circulating virus. Serum ATP levels found in PWH with the most severe neurocognitive impairment trigger the transcellular migration of HIV-infected leukocytes across the BBB in a JAM-A and LFA-1-dependent manner. We propose that targeting transcellular leukocyte transmigration could reduce or prevent the devastating consequences of HIV within the brains of PWH under ART. |
| first_indexed | 2024-04-25T01:41:25Z |
| format | Article |
| id | doaj.art-bed8c3b94fe143fe9bd4c8ecadece334 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-25T01:41:25Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-bed8c3b94fe143fe9bd4c8ecadece3342024-03-08T05:19:11ZengElsevieriScience2589-00422024-03-01273109236Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral eraCristian Hernandez0Anna Maria Gorska1Eliseo Eugenin2Department of Neurobiology, The University of Texas Medical Branch (UTMB), Galveston, TX, USADepartment of Neurobiology, The University of Texas Medical Branch (UTMB), Galveston, TX, USA; Department of Pathology, University of Oslo, Oslo, NorwayDepartment of Neurobiology, The University of Texas Medical Branch (UTMB), Galveston, TX, USA; Corresponding authorSummary: HIV-associated neurological compromise is observed in more than half of all people with HIV (PWH), even under antiretroviral therapy (ART). The mechanism has been associated with the early transmigration of HIV-infected monocytes across the BBB in a CCL2 and HIV replication-dependent manner. However, the mechanisms of chronic brain damage are unknown.We demonstrate that all PWH under ART have elevated circulating ATP levels that correlate with the onset of cognitive impairment even in the absence of a circulating virus. Serum ATP levels found in PWH with the most severe neurocognitive impairment trigger the transcellular migration of HIV-infected leukocytes across the BBB in a JAM-A and LFA-1-dependent manner. We propose that targeting transcellular leukocyte transmigration could reduce or prevent the devastating consequences of HIV within the brains of PWH under ART.http://www.sciencedirect.com/science/article/pii/S2589004224004577Molecular biologyMicrobiologyVirology |
| spellingShingle | Cristian Hernandez Anna Maria Gorska Eliseo Eugenin Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era iScience Molecular biology Microbiology Virology |
| title | Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| title_full | Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| title_fullStr | Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| title_full_unstemmed | Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| title_short | Mechanisms of HIV-mediated blood-brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| title_sort | mechanisms of hiv mediated blood brain barrier compromise and leukocyte transmigration under the current antiretroviral era |
| topic | Molecular biology Microbiology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224004577 |
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