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Sci Rep. 2016 Jul 1;6:28896. doi: 10.1038/srep28896.

Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner.

Author information

1
Department of Microbiology and Immunology, Liver Research Institute, Biomedical Sciences and SNUMRC, College of Medicine, Seoul National University, Seoul, Korea.
2
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.

Abstract

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.

PMID:
27363520
PMCID:
PMC4929463
DOI:
10.1038/srep28896
[Indexed for MEDLINE]
Free PMC Article

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