Cargando…
Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner
A peptide vaccine designed to induce T-cell immunity to telomerase, GV1001, has been shown to modulate cellular signaling pathways and confer a direct anti-cancer effect through the interaction with heat shock protein (HSP) 90 and 70. Here, we have found that GV1001 can modulate transactivation prot...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929463/ https://www.ncbi.nlm.nih.gov/pubmed/27363520 http://dx.doi.org/10.1038/srep28896 |
_version_ | 1782440613661114368 |
---|---|
author | Kim, Hong Choi, Myung-Soo Inn, Kyung-Soo Kim, Bum-Joon |
author_facet | Kim, Hong Choi, Myung-Soo Inn, Kyung-Soo Kim, Bum-Joon |
author_sort | Kim, Hong |
collection | PubMed |
description | A peptide vaccine designed to induce T-cell immunity to telomerase, GV1001, has been shown to modulate cellular signaling pathways and confer a direct anti-cancer effect through the interaction with heat shock protein (HSP) 90 and 70. Here, we have found that GV1001 can modulate transactivation protein-mediated human immunodeficiency virus (HIV)-1 transactivation in an HSP90-dependent manner. GV1001 treatment resulted in significant suppression of HIV-1 replication and rescue of infected cells from death by HIV-1. Transactivation of HIV-long terminal repeat (LTR) was inhibited by GV1001, indicating that GV1001 suppressed the transcription from proviral HIV DNA. The anti-HIV-1 activity of GV1001 was completely abrogated by an HSP90-neutralizing antibody, indicating that the antiviral activity depends on HSP90. Further mechanistic studies revealed that GV1001 suppresses basal NF-κB activation, which is required for HIV-1 LTR transactivation in an HSP90-dependent manner. Inhibition of LTR transactivation by GV1001 suggests its potential to suppress HIV-1 reactivation from latency. Indeed, PMA-mediated reactivation of HIV-1 from latent infected cells was suppressed by GV1001. The results suggest the potential therapeutic use of GV1001, a peptide proven to be safe for human use, as an anti-HIV-1 agent to suppress the reactivation from latently infected cells. |
format | Online Article Text |
id | pubmed-4929463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49294632016-07-06 Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner Kim, Hong Choi, Myung-Soo Inn, Kyung-Soo Kim, Bum-Joon Sci Rep Article A peptide vaccine designed to induce T-cell immunity to telomerase, GV1001, has been shown to modulate cellular signaling pathways and confer a direct anti-cancer effect through the interaction with heat shock protein (HSP) 90 and 70. Here, we have found that GV1001 can modulate transactivation protein-mediated human immunodeficiency virus (HIV)-1 transactivation in an HSP90-dependent manner. GV1001 treatment resulted in significant suppression of HIV-1 replication and rescue of infected cells from death by HIV-1. Transactivation of HIV-long terminal repeat (LTR) was inhibited by GV1001, indicating that GV1001 suppressed the transcription from proviral HIV DNA. The anti-HIV-1 activity of GV1001 was completely abrogated by an HSP90-neutralizing antibody, indicating that the antiviral activity depends on HSP90. Further mechanistic studies revealed that GV1001 suppresses basal NF-κB activation, which is required for HIV-1 LTR transactivation in an HSP90-dependent manner. Inhibition of LTR transactivation by GV1001 suggests its potential to suppress HIV-1 reactivation from latency. Indeed, PMA-mediated reactivation of HIV-1 from latent infected cells was suppressed by GV1001. The results suggest the potential therapeutic use of GV1001, a peptide proven to be safe for human use, as an anti-HIV-1 agent to suppress the reactivation from latently infected cells. Nature Publishing Group 2016-07-01 /pmc/articles/PMC4929463/ /pubmed/27363520 http://dx.doi.org/10.1038/srep28896 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Kim, Hong Choi, Myung-Soo Inn, Kyung-Soo Kim, Bum-Joon Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title | Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title_full | Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title_fullStr | Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title_full_unstemmed | Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title_short | Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner |
title_sort | inhibition of hiv-1 reactivation by a telomerase-derived peptide in a hsp90-dependent manner |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929463/ https://www.ncbi.nlm.nih.gov/pubmed/27363520 http://dx.doi.org/10.1038/srep28896 |
work_keys_str_mv | AT kimhong inhibitionofhiv1reactivationbyatelomerasederivedpeptideinahsp90dependentmanner AT choimyungsoo inhibitionofhiv1reactivationbyatelomerasederivedpeptideinahsp90dependentmanner AT innkyungsoo inhibitionofhiv1reactivationbyatelomerasederivedpeptideinahsp90dependentmanner AT kimbumjoon inhibitionofhiv1reactivationbyatelomerasederivedpeptideinahsp90dependentmanner |