Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Infectious Diseases |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000200150 |
Resumo: | ABSTRACT 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. |
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BSID-1 |
network_name_str |
Brazilian Journal of Infectious Diseases |
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spelling |
Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294NicotinamideLatency reversal agentsHistone deacetylases inhibitorMethyltransferase inhibitorsChaetocinBIX01294ABSTRACT 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.Brazilian Society of Infectious Diseases2020-04-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000200150Brazilian Journal of Infectious Diseases v.24 n.2 2020reponame:Brazilian Journal of Infectious Diseasesinstname:Brazilian Society of Infectious Diseases (BSID)instacron:BSID10.1016/j.bjid.2020.01.005info:eu-repo/semantics/openAccessSamer,SadiaArif,Muhammad ShoaibGiron,Leila BertoniZukurov,Jean Paulo LopesHunter,JamesSantillo,Bruna TeresaNamiyama,GisleneGalinskas,JulianaKomninakis,Shirley VasconcelosOshiro,Telma MiyukiSucupira,Maria CeciliaJanini,Luiz MarioDiaz,Ricardo Sobhieeng2020-06-24T00:00:00Zoai:scielo:S1413-86702020000200150Revistahttps://www.bjid.org.br/https://old.scielo.br/oai/scielo-oai.phpbjid@bjid.org.br||lgoldani@ufrgs.br1678-43911413-8670opendoar:2020-06-24T00:00Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)false |
dc.title.none.fl_str_mv |
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 |
Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 |
spellingShingle |
Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294 Samer,Sadia Nicotinamide Latency reversal agents Histone deacetylases inhibitor Methyltransferase inhibitors Chaetocin 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_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_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 |
author |
Samer,Sadia |
author_facet |
Samer,Sadia Arif,Muhammad Shoaib Giron,Leila Bertoni Zukurov,Jean Paulo Lopes Hunter,James Santillo,Bruna Teresa Namiyama,Gislene Galinskas,Juliana Komninakis,Shirley Vasconcelos Oshiro,Telma Miyuki Sucupira,Maria Cecilia Janini,Luiz Mario Diaz,Ricardo Sobhie |
author_role |
author |
author2 |
Arif,Muhammad Shoaib Giron,Leila Bertoni Zukurov,Jean Paulo Lopes Hunter,James Santillo,Bruna Teresa Namiyama,Gislene Galinskas,Juliana Komninakis,Shirley Vasconcelos Oshiro,Telma Miyuki Sucupira,Maria Cecilia Janini,Luiz Mario Diaz,Ricardo Sobhie |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Samer,Sadia Arif,Muhammad Shoaib Giron,Leila Bertoni Zukurov,Jean Paulo Lopes Hunter,James Santillo,Bruna Teresa Namiyama,Gislene Galinskas,Juliana Komninakis,Shirley Vasconcelos Oshiro,Telma Miyuki Sucupira,Maria Cecilia Janini,Luiz Mario Diaz,Ricardo Sobhie |
dc.subject.por.fl_str_mv |
Nicotinamide Latency reversal agents Histone deacetylases inhibitor Methyltransferase inhibitors Chaetocin BIX01294 |
topic |
Nicotinamide Latency reversal agents Histone deacetylases inhibitor Methyltransferase inhibitors Chaetocin BIX01294 |
description |
ABSTRACT 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-04-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000200150 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000200150 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.bjid.2020.01.005 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Brazilian Society of Infectious Diseases |
publisher.none.fl_str_mv |
Brazilian Society of Infectious Diseases |
dc.source.none.fl_str_mv |
Brazilian Journal of Infectious Diseases v.24 n.2 2020 reponame:Brazilian Journal of Infectious Diseases instname:Brazilian Society of Infectious Diseases (BSID) instacron:BSID |
instname_str |
Brazilian Society of Infectious Diseases (BSID) |
instacron_str |
BSID |
institution |
BSID |
reponame_str |
Brazilian Journal of Infectious Diseases |
collection |
Brazilian Journal of Infectious Diseases |
repository.name.fl_str_mv |
Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID) |
repository.mail.fl_str_mv |
bjid@bjid.org.br||lgoldani@ufrgs.br |
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1754209245037854720 |