Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294
Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX0129...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | Brazilian Journal of Infectious Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1413867020300192 |
| _version_ | 1828376769442349056 |
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| author | Sadia Samer Muhammad Shoaib Arif Leila Bertoni Giron Jean Paulo Lopes Zukurov James Hunter Bruna Teresa Santillo Gislene Namiyama Juliana Galinskas Shirley Vasconcelos Komninakis Telma Miyuki Oshiro Maria Cecilia Sucupira Luiz Mario Janini Ricardo Sobhie Diaz |
| author_facet | Sadia Samer Muhammad Shoaib Arif Leila Bertoni Giron Jean Paulo Lopes Zukurov James Hunter Bruna Teresa Santillo Gislene Namiyama Juliana Galinskas Shirley Vasconcelos Komninakis Telma Miyuki Oshiro Maria Cecilia Sucupira Luiz Mario Janini Ricardo Sobhie Diaz |
| author_sort | Sadia Samer |
| collection | DOAJ |
| description | Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use. |
| first_indexed | 2024-04-14T08:03:47Z |
| format | Article |
| id | doaj.art-dc4c4bab15404e79a03bd50da2bb1f03 |
| institution | Directory Open Access Journal |
| issn | 1413-8670 |
| language | English |
| last_indexed | 2024-04-14T08:03:47Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brazilian Journal of Infectious Diseases |
| spelling | doaj.art-dc4c4bab15404e79a03bd50da2bb1f032022-12-22T02:04:49ZengElsevierBrazilian Journal of Infectious Diseases1413-86702020-03-01242150159Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294Sadia Samer0Muhammad Shoaib Arif1Leila Bertoni Giron2Jean Paulo Lopes Zukurov3James Hunter4Bruna Teresa Santillo5Gislene Namiyama6Juliana Galinskas7Shirley Vasconcelos Komninakis8Telma Miyuki Oshiro9Maria Cecilia Sucupira10Luiz Mario Janini11Ricardo Sobhie Diaz12Yerkes National Primate Research Center, Emory University, Atlanta, GeorgiaDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, USAWistar Institute, Philadelphia, USADepartment of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, BrazilDepartment of Medicine, Federal University of Sao Paulo, São Paulo, SP, BrazilDepartment of Dermatology, University of Sao Paulo, São Paulo, SP, BrazilDepartment of Electron Microscopy, Institute of Adolfo Lutz, São Paulo, SP, BrazilDepartment of Medicine, Federal University of Sao Paulo, São Paulo, SP, BrazilDepartment of Medicine, Federal University of Sao Paulo, São Paulo, SP, BrazilDepartment of Dermatology, University of Sao Paulo, São Paulo, SP, BrazilDepartment of Medicine, Federal University of Sao Paulo, São Paulo, SP, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, BrazilDepartment of Medicine, Federal University of Sao Paulo, São Paulo, SP, Brazil; Corresponding authorBackground: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.http://www.sciencedirect.com/science/article/pii/S1413867020300192NicotinamideLatency reversal agentsHistone deacetylases inhibitorMethyltransferase inhibitorsChaetocinBIX01294 |
| spellingShingle | Sadia Samer Muhammad Shoaib Arif Leila Bertoni Giron Jean Paulo Lopes Zukurov James Hunter Bruna Teresa Santillo Gislene Namiyama Juliana Galinskas Shirley Vasconcelos Komninakis Telma Miyuki Oshiro Maria Cecilia Sucupira Luiz Mario Janini Ricardo Sobhie Diaz Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 Brazilian Journal of Infectious Diseases Nicotinamide Latency reversal agents Histone deacetylases inhibitor Methyltransferase inhibitors Chaetocin BIX01294 |
| title | Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
| title_full | Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
| title_fullStr | Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
| title_full_unstemmed | Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
| title_short | Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
| title_sort | nicotinamide activates latent hiv 1 ex vivo in art suppressed individuals revealing higher potency than the association of two methyltransferase inhibitors chaetocin and bix01294 |
| topic | Nicotinamide Latency reversal agents Histone deacetylases inhibitor Methyltransferase inhibitors Chaetocin BIX01294 |
| url | http://www.sciencedirect.com/science/article/pii/S1413867020300192 |
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