title: Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner.
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.
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Biomedical Sciences and SNUMRC, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Myung-Soo
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.affiliation: Department of Microbiology and Immunology, Liver Research Institute, Biomedical Sciences and SNUMRC, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009369:Neoplasms / Q000473:pathology / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D019098:Telomerase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D022223:Vaccines, Subunit / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects* / Q000235:genetics; D017735:Virus Latency / Q000187:drug effects / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D018841:HSP90 Heat-Shock Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; C514987:GV1001 peptide; D019098:Telomerase