دورية أكاديمية
Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat
| العنوان: | Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat |
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| المؤلفون: | Olesen, Rikke, Vigano, Selena, Rasmussen, Thomas A, Søgaard, Ole S, Ouyang, Zhengyu, Buzon, Maria, Bashirova, Arman, Carrington, Mary, Palmer, Sarah, Brinkmann, Christel R, Yu, Xu G, Østergaard, Lars Jørgen, Tolstrup, Martin, Lichterfeld, Mathias |
| المصدر: | Olesen , R , Vigano , S , Rasmussen , T A , Søgaard , O S , Ouyang , Z , Buzon , M , Bashirova , A , Carrington , M , Palmer , S , Brinkmann , C R , Yu , X G , Østergaard , L J , Tolstrup , M & Lichterfeld , M 2015 , ' Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline during Latency-Reversing Treatment with Panobinostat ' , Journal of Virology , vol. 89 , no. 20 , pp. 10176-89 . https://doi.org/10.1128/JVI.01484-15Test |
| سنة النشر: | 2015 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | Antigens, CD, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Count, DNA, Viral, Dendritic Cells, Drug Administration Schedule, Gene Expression, Genotype, HIV Infections, HIV-1, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Immunity, Innate, Indoles, Interleukins, Killer Cells, Natural, Virus Latency |
| الوصف: | UNLABELLED: The pharmaceutical reactivation of dormant HIV-1 proviruses by histone deacetylase inhibitors (HDACi) represents a possible strategy to reduce the reservoir of HIV-1-infected cells in individuals treated with suppressive combination antiretroviral therapy (cART). However, the effects of such latency-reversing agents on the viral reservoir size are likely to be influenced by host immune responses. Here, we analyzed the immune factors associated with changes in proviral HIV-1 DNA levels during treatment with the potent HDACi panobinostat in a human clinical trial involving 15 cART-treated HIV-1-infected patients. We observed that the magnitude, breadth, and cytokine secretion profile of HIV-1-specific CD8 T cell responses were unrelated to changes in HIV-1 DNA levels in CD4 T cells during panobinostat treatment. In contrast, the proportions of CD3(-) CD56(+) total NK cells and CD16(+) CD56(dim) NK cells were inversely correlated with HIV-1 DNA levels throughout the study, and changes in HIV-1 DNA levels during panobinostat treatment were negatively associated with the corresponding changes in CD69(+) NK cells. Decreasing levels of HIV-1 DNA during latency-reversing treatment were also related to the proportions of plasmacytoid dendritic cells, to distinct expression patterns of interferon-stimulated genes, and to the expression of the IL28B CC genotype. Together, these data suggest that innate immune activity can critically modulate the effects of latency-reversing agents on the viral reservoir and may represent a target for future immunotherapeutic interventions in HIV-1 eradication studies. IMPORTANCE: Currently available antiretroviral drugs are highly effective in suppressing HIV-1 replication, but the virus persists, despite treatment, in a latent form that does not actively express HIV-1 gene products. One approach to eliminate these cells, colloquially termed the "shock-and-kill" strategy, focuses on the use of latency-reversing agents that induce active viral gene expression in latently ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://pure.au.dk/portal/en/publications/6d059326-3c05-4a5b-a3e2-b69d7ac305ecTest |
| DOI: | 10.1128/JVI.01484-15 |
| الإتاحة: | https://doi.org/10.1128/JVI.01484-15Test https://pure.au.dk/portal/en/publications/6d059326-3c05-4a5b-a3e2-b69d7ac305ecTest |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.951C75A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/JVI.01484-15 |
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