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Title: A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”

Abstract

Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A “kick and kill” strategy proposes “kick” of the latent HIV to an active HIV to eventually be “killed”. Latency-reverting agents that can perform the “kick” function are under development and have shown promise. Management of the infected cells not to produce virions after the “kick” step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55Gag and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus “locked-in” subsequently induces apoptosis of the host cells. This “lock-in and apoptosis” approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the “kick” and “kill” steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body

Authors:
; ORCiD logo [1];  [2];  [1];  [1];  [1]; ORCiD logo [3];  [1];  [1];  [1];  [1];  [1]
  1. Kumamoto Univ. (Japan)
  2. Kumamoto Health Science Univ. (Japan)
  3. SLAC National Accelerator Lab., Menlo Park, CA (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1390617
Grant/Contract Number:
AC02-76SF00515
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Tateishi, Hiroshi, Monde, Kazuaki, Anraku, Kensaku, Koga, Ryoko, Hayashi, Yuya, Ciftci, Halil Ibrahim, DeMirci, Hasan, Higashi, Taishi, Motoyama, Keiichi, Arima, Hidetoshi, Otsuka, Masami, and Fujita, Mikako. A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”. United States: N. p., 2017. Web. doi:10.1038/s41598-017-09129-w.
Tateishi, Hiroshi, Monde, Kazuaki, Anraku, Kensaku, Koga, Ryoko, Hayashi, Yuya, Ciftci, Halil Ibrahim, DeMirci, Hasan, Higashi, Taishi, Motoyama, Keiichi, Arima, Hidetoshi, Otsuka, Masami, & Fujita, Mikako. A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”. United States. doi:10.1038/s41598-017-09129-w.
Tateishi, Hiroshi, Monde, Kazuaki, Anraku, Kensaku, Koga, Ryoko, Hayashi, Yuya, Ciftci, Halil Ibrahim, DeMirci, Hasan, Higashi, Taishi, Motoyama, Keiichi, Arima, Hidetoshi, Otsuka, Masami, and Fujita, Mikako. Mon . "A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”". United States. doi:10.1038/s41598-017-09129-w. https://www.osti.gov/servlets/purl/1390617.
@article{osti_1390617,
title = {A clue to unprecedented strategy to HIV eradication: “Lock-in and apoptosis”},
author = {Tateishi, Hiroshi and Monde, Kazuaki and Anraku, Kensaku and Koga, Ryoko and Hayashi, Yuya and Ciftci, Halil Ibrahim and DeMirci, Hasan and Higashi, Taishi and Motoyama, Keiichi and Arima, Hidetoshi and Otsuka, Masami and Fujita, Mikako},
abstractNote = {Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A “kick and kill” strategy proposes “kick” of the latent HIV to an active HIV to eventually be “killed”. Latency-reverting agents that can perform the “kick” function are under development and have shown promise. Management of the infected cells not to produce virions after the “kick” step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55Gag and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding. The infecting virus thus “locked-in” subsequently induces apoptosis of the host cells. This “lock-in and apoptosis” approach performed by our novel compound in HIV-infected cells provides a means to bridge the gap between the “kick” and “kill” steps of this eradication strategy. By building upon previous progress in latency reverting agents, our compound appears to provide a promising step toward the goal of HIV eradication from the body},
doi = {10.1038/s41598-017-09129-w},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {Mon Aug 21 00:00:00 EDT 2017},
month = {Mon Aug 21 00:00:00 EDT 2017}
}

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