Tat-specific antibodies associated with better HIV-associated motor function
Abstract Tat is a transactivator of HIV transcription that can be secreted to affect nearby cells. Deleterious central nervous system effects of extracellular Tat include dopaminergic neuron dysfunction, raising the possibility that Tat secretion may be linked to Parkinsonian motor features seen in...
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| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12624-0 |
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| author | Catarina E. Hioe Clauvis Kunkeng Yengo Xiaomei Liu Reuben Davis Gospel Enyindah-Asonye Jéromine Klingler Alex F. Tang Juan C. Bandres Anuradha Ganesan Tahaniyat Lalani Joseph Yabes Brian K. Agan Xiaokun Liu David J. Volsky Susan Morgello Jessica Robinson-Papp |
| author_facet | Catarina E. Hioe Clauvis Kunkeng Yengo Xiaomei Liu Reuben Davis Gospel Enyindah-Asonye Jéromine Klingler Alex F. Tang Juan C. Bandres Anuradha Ganesan Tahaniyat Lalani Joseph Yabes Brian K. Agan Xiaokun Liu David J. Volsky Susan Morgello Jessica Robinson-Papp |
| author_sort | Catarina E. Hioe |
| collection | DOAJ |
| description | Abstract Tat is a transactivator of HIV transcription that can be secreted to affect nearby cells. Deleterious central nervous system effects of extracellular Tat include dopaminergic neuron dysfunction, raising the possibility that Tat secretion may be linked to Parkinsonian motor features seen in people with HIV (PWH). This study examined the potential association of anti-Tat antibodies and extrapyramidal motor dysfunction in PWH. In 42 PWH who were chronically infected and characterized for neurological abnormalities, anti-Tat IgG levels were lower in individuals with more severe extrapyramidal motor abnormalities as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). The association was observed specifically with IgG against the cysteine-rich Tat region. However, the IgG responses to Tat were weak in comparison to responses against the other HIV antigens. This disparity was evident in plasma and cerebrospinal fluid, and was also seen in early infection, before antiretroviral therapy. When the effects of antibodies on Tat function were evaluated, PWH plasma had no activity against Tat-induced transactivation, while Tat-immunized mouse and rabbit sera exhibited a potent inhibitory activity. These data provide initial evidence for a protective potential of anti-Tat antibodies and raise the possibility that a therapeutic Tat vaccine might alleviate clinical signs of HIV-associated dopaminergic dysfunction. |
| format | Article |
| id | doaj-art-ce2adac799d64846862da87ad3f16339 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ce2adac799d64846862da87ad3f163392025-08-20T03:04:30ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-12624-0Tat-specific antibodies associated with better HIV-associated motor functionCatarina E. Hioe0Clauvis Kunkeng Yengo1Xiaomei Liu2Reuben Davis3Gospel Enyindah-Asonye4Jéromine Klingler5Alex F. Tang6Juan C. Bandres7Anuradha Ganesan8Tahaniyat Lalani9Joseph Yabes10Brian K. Agan11Xiaokun Liu12David J. Volsky13Susan Morgello14Jessica Robinson-Papp15James J. Peters VA Medical CenterJames J. Peters VA Medical CenterJames J. Peters VA Medical CenterDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiJames J. Peters VA Medical CenterDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiJames J. Peters VA Medical CenterDivision of Infectious Diseases, Walter Reed National Military Medical CenterInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesInfectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health SciencesDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiDepartment of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiAbstract Tat is a transactivator of HIV transcription that can be secreted to affect nearby cells. Deleterious central nervous system effects of extracellular Tat include dopaminergic neuron dysfunction, raising the possibility that Tat secretion may be linked to Parkinsonian motor features seen in people with HIV (PWH). This study examined the potential association of anti-Tat antibodies and extrapyramidal motor dysfunction in PWH. In 42 PWH who were chronically infected and characterized for neurological abnormalities, anti-Tat IgG levels were lower in individuals with more severe extrapyramidal motor abnormalities as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). The association was observed specifically with IgG against the cysteine-rich Tat region. However, the IgG responses to Tat were weak in comparison to responses against the other HIV antigens. This disparity was evident in plasma and cerebrospinal fluid, and was also seen in early infection, before antiretroviral therapy. When the effects of antibodies on Tat function were evaluated, PWH plasma had no activity against Tat-induced transactivation, while Tat-immunized mouse and rabbit sera exhibited a potent inhibitory activity. These data provide initial evidence for a protective potential of anti-Tat antibodies and raise the possibility that a therapeutic Tat vaccine might alleviate clinical signs of HIV-associated dopaminergic dysfunction.https://doi.org/10.1038/s41598-025-12624-0HIVTatAntibodiesEpitopesDopaminergic neuronNeuropathogenesis |
| spellingShingle | Catarina E. Hioe Clauvis Kunkeng Yengo Xiaomei Liu Reuben Davis Gospel Enyindah-Asonye Jéromine Klingler Alex F. Tang Juan C. Bandres Anuradha Ganesan Tahaniyat Lalani Joseph Yabes Brian K. Agan Xiaokun Liu David J. Volsky Susan Morgello Jessica Robinson-Papp Tat-specific antibodies associated with better HIV-associated motor function Scientific Reports HIV Tat Antibodies Epitopes Dopaminergic neuron Neuropathogenesis |
| title | Tat-specific antibodies associated with better HIV-associated motor function |
| title_full | Tat-specific antibodies associated with better HIV-associated motor function |
| title_fullStr | Tat-specific antibodies associated with better HIV-associated motor function |
| title_full_unstemmed | Tat-specific antibodies associated with better HIV-associated motor function |
| title_short | Tat-specific antibodies associated with better HIV-associated motor function |
| title_sort | tat specific antibodies associated with better hiv associated motor function |
| topic | HIV Tat Antibodies Epitopes Dopaminergic neuron Neuropathogenesis |
| url | https://doi.org/10.1038/s41598-025-12624-0 |
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