Cargando…

Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro

Latency-reversing agents (LRAs) are considered a potential tool to cure human immunodeficiency virus type 1 (HIV-1) infection, but when they are taken alone, virus production by reactivated cells and subsequent infection will occur. Hence, it is crucial to simultaneously take appropriate measures to...

Descripción completa

Detalles Bibliográficos
Autores principales: Hattori, Shin-ichiro, Matsuda, Kouki, Tsuchiya, Kiyoto, Gatanaga, Hiroyuki, Oka, Shinichi, Yoshimura, Kazuhisa, Mitsuya, Hiroaki, Maeda, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156138/
https://www.ncbi.nlm.nih.gov/pubmed/30283406
http://dx.doi.org/10.3389/fmicb.2018.02022
_version_ 1783358041808175104
author Hattori, Shin-ichiro
Matsuda, Kouki
Tsuchiya, Kiyoto
Gatanaga, Hiroyuki
Oka, Shinichi
Yoshimura, Kazuhisa
Mitsuya, Hiroaki
Maeda, Kenji
author_facet Hattori, Shin-ichiro
Matsuda, Kouki
Tsuchiya, Kiyoto
Gatanaga, Hiroyuki
Oka, Shinichi
Yoshimura, Kazuhisa
Mitsuya, Hiroaki
Maeda, Kenji
author_sort Hattori, Shin-ichiro
collection PubMed
description Latency-reversing agents (LRAs) are considered a potential tool to cure human immunodeficiency virus type 1 (HIV-1) infection, but when they are taken alone, virus production by reactivated cells and subsequent infection will occur. Hence, it is crucial to simultaneously take appropriate measures to prevent such secondary HIV-1 infection. In this regard, a strategy to minimize the production of infectious viruses from LRA-reactivated cells is worth pursuing. Here, we focused on a second mitochondria-derived activator of caspases (Smac) mimetic, birinapant, to induce apoptosis in latent HIV-1-infected cells. When birinapant was administered alone, it only slightly increased the expression of caspase-3. However, in combination with an LRA (e.g., PEP005), it strongly induced the expression of caspase-3 followed by enhanced apoptosis. Importantly, the combination eliminated reactivated cells and drastically reduced HIV-1 production. Finally, we found that birinapant decreased the mRNA expression of HIV-1 that was induced by PEP005 in the primary CD4(+) T-cells from HIV-1-carrying patients as well. These results suggest that the combination of an LRA and an “apoptosis-inducing” agent, such as a Smac mimetic, is a possible treatment option to decrease HIV-1 reservoirs without the occurrence of HIV-1 production by reactivated cells.
format Online
Article
Text
id pubmed-6156138
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-61561382018-10-03 Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro Hattori, Shin-ichiro Matsuda, Kouki Tsuchiya, Kiyoto Gatanaga, Hiroyuki Oka, Shinichi Yoshimura, Kazuhisa Mitsuya, Hiroaki Maeda, Kenji Front Microbiol Microbiology Latency-reversing agents (LRAs) are considered a potential tool to cure human immunodeficiency virus type 1 (HIV-1) infection, but when they are taken alone, virus production by reactivated cells and subsequent infection will occur. Hence, it is crucial to simultaneously take appropriate measures to prevent such secondary HIV-1 infection. In this regard, a strategy to minimize the production of infectious viruses from LRA-reactivated cells is worth pursuing. Here, we focused on a second mitochondria-derived activator of caspases (Smac) mimetic, birinapant, to induce apoptosis in latent HIV-1-infected cells. When birinapant was administered alone, it only slightly increased the expression of caspase-3. However, in combination with an LRA (e.g., PEP005), it strongly induced the expression of caspase-3 followed by enhanced apoptosis. Importantly, the combination eliminated reactivated cells and drastically reduced HIV-1 production. Finally, we found that birinapant decreased the mRNA expression of HIV-1 that was induced by PEP005 in the primary CD4(+) T-cells from HIV-1-carrying patients as well. These results suggest that the combination of an LRA and an “apoptosis-inducing” agent, such as a Smac mimetic, is a possible treatment option to decrease HIV-1 reservoirs without the occurrence of HIV-1 production by reactivated cells. Frontiers Media S.A. 2018-09-19 /pmc/articles/PMC6156138/ /pubmed/30283406 http://dx.doi.org/10.3389/fmicb.2018.02022 Text en Copyright © 2018 Hattori, Matsuda, Tsuchiya, Gatanaga, Oka, Yoshimura, Mitsuya and Maeda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hattori, Shin-ichiro
Matsuda, Kouki
Tsuchiya, Kiyoto
Gatanaga, Hiroyuki
Oka, Shinichi
Yoshimura, Kazuhisa
Mitsuya, Hiroaki
Maeda, Kenji
Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title_full Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title_fullStr Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title_full_unstemmed Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title_short Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
title_sort combination of a latency-reversing agent with a smac mimetic minimizes secondary hiv-1 infection in vitro
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156138/
https://www.ncbi.nlm.nih.gov/pubmed/30283406
http://dx.doi.org/10.3389/fmicb.2018.02022
work_keys_str_mv AT hattorishinichiro combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT matsudakouki combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT tsuchiyakiyoto combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT gatanagahiroyuki combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT okashinichi combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT yoshimurakazuhisa combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT mitsuyahiroaki combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro
AT maedakenji combinationofalatencyreversingagentwithasmacmimeticminimizessecondaryhiv1infectioninvitro