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

Journal Article · · Scientific Reports
;  [1];  [2];  [1];  [1];  [1];  [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)
+ Show Author Affiliations
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
Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1390617
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 7; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs journal May 2019
Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro journal September 2018
Design, Synthesis and Biological Evaluation of Pentacyclic Triterpene Derivatives: Optimization of Anti-ABL Kinase Activity journal September 2019
A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity journal January 2020
Use of ‘eradication’ in HIV cure-related research: a public health debate journal February 2018
Use of ‘eradication’ in HIV cure-related research: a public health debate text January 2018
Serial Femtosecond X-Ray Diffraction of HIV-1 Gag MA-IP6 Microcrystals at Ambient Temperature journal April 2019
Design, Synthesis, and Biological Evaluation of Novel 1,3,4-Thiadiazole Derivatives as Potential Antitumor Agents against Chronic Myelogenous Leukemia: Striking Effect of Nitrothiazole Moiety journal December 2017
Antileukemic Activity of Twig Components of Caucasian Beech in Turkey journal October 2019

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