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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Hong, Choi, Myung-Soo, Inn, Kyung-Soo, Kim, Bum-Joon
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