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Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner
HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to pu...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886842/ https://www.ncbi.nlm.nih.gov/pubmed/20585398 http://dx.doi.org/10.1371/journal.pone.0011160 |
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author | Mehla, Rajeev Bivalkar-Mehla, Shalmali Zhang, Ruonan Handy, Indhira Albrecht, Helmut Giri, Shailendra Nagarkatti, Prakash Nagarkatti, Mitzi Chauhan, Ashok |
author_facet | Mehla, Rajeev Bivalkar-Mehla, Shalmali Zhang, Ruonan Handy, Indhira Albrecht, Helmut Giri, Shailendra Nagarkatti, Prakash Nagarkatti, Mitzi Chauhan, Ashok |
author_sort | Mehla, Rajeev |
collection | PubMed |
description | HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs. |
format | Text |
id | pubmed-2886842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28868422010-06-22 Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner Mehla, Rajeev Bivalkar-Mehla, Shalmali Zhang, Ruonan Handy, Indhira Albrecht, Helmut Giri, Shailendra Nagarkatti, Prakash Nagarkatti, Mitzi Chauhan, Ashok PLoS One Research Article HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs. Public Library of Science 2010-06-16 /pmc/articles/PMC2886842/ /pubmed/20585398 http://dx.doi.org/10.1371/journal.pone.0011160 Text en Mehla et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mehla, Rajeev Bivalkar-Mehla, Shalmali Zhang, Ruonan Handy, Indhira Albrecht, Helmut Giri, Shailendra Nagarkatti, Prakash Nagarkatti, Mitzi Chauhan, Ashok Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title | Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title_full | Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title_fullStr | Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title_full_unstemmed | Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title_short | Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner |
title_sort | bryostatin modulates latent hiv-1 infection via pkc and ampk signaling but inhibits acute infection in a receptor independent manner |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886842/ https://www.ncbi.nlm.nih.gov/pubmed/20585398 http://dx.doi.org/10.1371/journal.pone.0011160 |
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