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:
-
[1];
[3];
- Kumamoto Univ. (Japan)
- Kumamoto Health Science Univ. (Japan)
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1390617
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- 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. https://doi.org/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. https://doi.org/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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Works referenced in this record:
Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers
journal, September 2000
- Ozaki, S.; DeWald, D. B.; Shope, J. C.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 21
In Vitro and In Vivo Gene Transfer by an Optimized α-Cyclodextrin Conjugate with Polyamidoamine Dendrimer
journal, March 2003
- Kihara, Fumihiro; Arima, Hidetoshi; Tsutsumi, Toshihito
- Bioconjugate Chemistry, Vol. 14, Issue 2
HIV/AIDS eradication
journal, July 2013
- Marsden, Matthew D.; Zack, Jerome A.
- Bioorganic & Medicinal Chemistry Letters, Vol. 23, Issue 14
Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane
journal, October 2004
- Ono, A.; Ablan, S. D.; Lockett, S. J.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 41
Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors
journal, August 2013
- Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi
- Advanced Drug Delivery Reviews, Vol. 65, Issue 9
Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers
journal, September 2000
- Ozaki, S.; DeWald, D. B.; Shope, J. C.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 21
Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents
journal, October 2015
- Karabacak, Muhammed; Altıntop, Mehlika; İbrahim Çiftçi, Halil
- Molecules, Vol. 20, Issue 10
Design and synthesis of biotinylated inositol phosphates relevant to the biotin–avidin techniques
journal, January 2008
- Anraku, Kensaku; Inoue, Teruhiko; Sugimoto, Kenji
- Organic & Biomolecular Chemistry, Vol. 6, Issue 10
Structural and Molecular Determinants of Membrane Binding by the HIV-1 Matrix Protein
journal, April 2016
- Mercredi, Peter Y.; Bucca, Nadine; Loeliger, Burk
- Journal of Molecular Biology, Vol. 428, Issue 8
Plasma membrane rafts play a critical role in HIV-1 assembly and release
journal, November 2001
- Ono, A.; Freed, E. O.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 24
Inhibitory effect of siRNA complexes with polyamidoamine dendrimer/α-cyclodextrin conjugate (generation 3, G3) on endogenous gene expression
journal, October 2011
- Arima, Hidetoshi; Tsutsumi, Toshihito; Yoshimatsu, Ayumi
- European Journal of Pharmaceutical Sciences, Vol. 44, Issue 3
Enhancement of Gene Expression by Polyamidoamine Dendrimer Conjugates with α-, β-, and γ-Cyclodextrins
journal, July 2001
- Arima, Hidetoshi; Kihara, Fumihiro; Hirayama, Fumitoshi
- Bioconjugate Chemistry, Vol. 12, Issue 4
HIV-1 infection of non-dividing cells: evidence that the amino-terminal basic region of the viral matrix protein is important for Gag processing but not for post-entry nuclear import
journal, August 1997
- Fouchier, R. A. M.
- The EMBO Journal, Vol. 16, Issue 15
Plasma membrane rafts play a critical role in HIV-1 assembly and release
journal, November 2001
- Ono, A.; Freed, E. O.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 24
HIV reservoirs: what, where and how to target them
journal, November 2015
- Churchill, Melissa J.; Deeks, Steven G.; Margolis, David M.
- Nature Reviews Microbiology, Vol. 14, Issue 1
Coarse-Grained Simulations of the HIV-1 Matrix Protein Anchoring: Revisiting Its Assembly on Membrane Domains
journal, February 2014
- Charlier, Landry; Louet, Maxime; Chaloin, Laurent
- Biophysical Journal, Vol. 106, Issue 3
Design and synthesis of biotinylated inositol phosphates relevant to the biotin–avidin techniques
journal, January 2008
- Anraku, Kensaku; Inoue, Teruhiko; Sugimoto, Kenji
- Organic & Biomolecular Chemistry, Vol. 6, Issue 10
Recent advances in cyclodextrin delivery techniques
journal, June 2015
- Arima, Hidetoshi; Hayashi, Yuya; Higashi, Taishi
- Expert Opinion on Drug Delivery, Vol. 12, Issue 9
Expression of HIV-1 accessory protein Vif is controlled uniquely to be low and optimal by proteasome degradation
journal, July 2004
- Fujita, M.; Akari, H.; Sakurai, A.
- Microbes and Infection, Vol. 6, Issue 9
Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate derivatives exhibiting high-affinity binding for the HIV-1 MA domain
journal, January 2014
- Tateishi, Hiroshi; Anraku, Kensaku; Koga, Ryoko
- Org. Biomol. Chem., Vol. 12, Issue 27
Interaction between the Human Immunodeficiency Virus Type 1 Gag Matrix Domain and Phosphatidylinositol-(4,5)-Bisphosphate Is Essential for Efficient Gag Membrane Binding
journal, December 2007
- Chukkapalli, V.; Hogue, I. B.; Boyko, V.
- Journal of Virology, Vol. 82, Issue 5
Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
journal, January 1986
- Adachi, A.; Gendelman, H. E.; Koenig, S.
- Journal of Virology, Vol. 59, Issue 2
Recent advances in cyclodextrin delivery techniques
journal, June 2015
- Arima, Hidetoshi; Hayashi, Yuya; Higashi, Taishi
- Expert Opinion on Drug Delivery, Vol. 12, Issue 9
Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly
journal, July 2006
- Saad, J. S.; Miller, J.; Tai, J.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 30
Enhancement of gene transfer activity mediated by mannosylated dendrimer/α-cyclodextrin conjugate (generation 3, G3)
journal, November 2006
- Arima, Hidetoshi; Chihara, Yuko; Arizono, Masayo
- Journal of Controlled Release, Vol. 116, Issue 1
Challenges and strategies for the eradication of the HIV reservoir
journal, October 2016
- Kimata, Jason T.; Rice, Andrew P.; Wang, Jin
- Current Opinion in Immunology, Vol. 42
Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly
journal, July 2006
- Saad, J. S.; Miller, J.; Tai, J.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 30
Which therapeutic strategy will achieve a cure for HIV-1?
journal, June 2016
- Cillo, Anthony R.; Mellors, John W.
- Current Opinion in Virology, Vol. 18
Human Endogenous Retrovirus K Gag Coassembles with HIV-1 Gag and Reduces the Release Efficiency and Infectivity of HIV-1
journal, August 2012
- Monde, K.; Contreras-Galindo, R.; Kaplan, M. H.
- Journal of Virology, Vol. 86, Issue 20
Enhancement of gene transfer activity mediated by mannosylated dendrimer/α-cyclodextrin conjugate (generation 3, G3)
journal, November 2006
- Arima, Hidetoshi; Chihara, Yuko; Arizono, Masayo
- Journal of Controlled Release, Vol. 116, Issue 1
Inhibitory effect of siRNA complexes with polyamidoamine dendrimer/α-cyclodextrin conjugate (generation 3, G3) on endogenous gene expression
journal, October 2011
- Arima, Hidetoshi; Tsutsumi, Toshihito; Yoshimatsu, Ayumi
- European Journal of Pharmaceutical Sciences, Vol. 44, Issue 3
Apoptotic cell clearance: basic biology and therapeutic potential
journal, January 2014
- Poon, Ivan K. H.; Lucas, Christopher D.; Rossi, Adriano G.
- Nature Reviews Immunology, Vol. 14, Issue 3
Apoptotic cell clearance: basic biology and therapeutic potential
journal, January 2014
- Poon, Ivan K. H.; Lucas, Christopher D.; Rossi, Adriano G.
- Nature Reviews Immunology, Vol. 14, Issue 3
Suicide gene therapy in cancer: Where do we stand now?
journal, November 2012
- Duarte, Sónia; Carle, Georges; Faneca, Henrique
- Cancer Letters, Vol. 324, Issue 2
Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors
journal, August 2013
- Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi
- Advanced Drug Delivery Reviews, Vol. 65, Issue 9
Enhancement of Gene Expression by Polyamidoamine Dendrimer Conjugates with α-, β-, and γ-Cyclodextrins
journal, July 2001
- Arima, Hidetoshi; Kihara, Fumihiro; Hirayama, Fumitoshi
- Bioconjugate Chemistry, Vol. 12, Issue 4
HIV-1 infection of non-dividing cells: evidence that the amino-terminal basic region of the viral matrix protein is important for Gag processing but not for post-entry nuclear import
journal, August 1997
- Fouchier, R. A. M.
- The EMBO Journal, Vol. 16, Issue 15
Which therapeutic strategy will achieve a cure for HIV-1?
journal, June 2016
- Cillo, Anthony R.; Mellors, John W.
- Current Opinion in Virology, Vol. 18
Highly Sensitive Analysis of the Interaction between HIV-1 Gag and Phosphoinositide Derivatives Based on Surface Plasmon Resonance
journal, June 2010
- Anraku, Kensaku; Fukuda, Ryota; Takamune, Nobutoki
- Biochemistry, Vol. 49, Issue 25
In Vitro and In Vivo Gene Transfer by an Optimized α-Cyclodextrin Conjugate with Polyamidoamine Dendrimer
journal, March 2003
- Kihara, Fumihiro; Arima, Hidetoshi; Tsutsumi, Toshihito
- Bioconjugate Chemistry, Vol. 14, Issue 2
The Vif and Gag proteins of human immunodeficiency virus type 1 colocalize in infected human T cells.
journal, January 1997
- Simon, J. H.; Fouchier, R. A.; Southerling, T. E.
- Journal of virology, Vol. 71, Issue 7
Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
journal, January 1986
- Adachi, A.; Gendelman, H. E.; Koenig, S.
- Journal of Virology, Vol. 59, Issue 2
The Vif and Gag proteins of human immunodeficiency virus type 1 colocalize in infected human T cells.
journal, January 1997
- Simon, J. H.; Fouchier, R. A.; Southerling, T. E.
- Journal of virology, Vol. 71, Issue 7
Works referencing / citing this record:
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journal, September 2018
- Hattori, Shin-ichiro; Matsuda, Kouki; Tsuchiya, Kiyoto
- Frontiers in Microbiology, Vol. 9
Antileukemic Activity of Twig Components of Caucasian Beech in Turkey
journal, October 2019
- Shida, Wataru; Tateishi, Hiroshi; Tahara, Yurika
- Molecules, Vol. 24, Issue 21
Use of ‘eradication’ in HIV cure-related research: a public health debate
text, January 2018
- Stuart, Luter,; Jerome, Galea,; Sara, Gianella,
- BioMed Central
Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs
journal, May 2019
- Sadowski, Ivan; Hashemi, Farhad B.
- Cellular and Molecular Life Sciences, Vol. 76, Issue 18
Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro
journal, September 2018
- Hattori, Shin-ichiro; Matsuda, Kouki; Tsuchiya, Kiyoto
- Frontiers in Microbiology, Vol. 9
Design, Synthesis and Biological Evaluation of Pentacyclic Triterpene Derivatives: Optimization of Anti-ABL Kinase Activity
journal, September 2019
- I. Ciftci, Halil; O. Radwan, Mohamed; E. Ozturk, Safiye
- Molecules, Vol. 24, Issue 19
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
- Altıntop, Mehlika; Ciftci, Halil; Radwan, Mohamed
- Molecules, Vol. 23, Issue 1
Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs
journal, May 2019
- Sadowski, Ivan; Hashemi, Farhad B.
- Cellular and Molecular Life Sciences, Vol. 76, Issue 18
Use of ‘eradication’ in HIV cure-related research: a public health debate
journal, February 2018
- Dubé, Karine; Luter, Stuart; Lesnar, Breanne
- BMC Public Health, Vol. 18, Issue 1
Serial Femtosecond X-Ray Diffraction of HIV-1 Gag MA-IP6 Microcrystals at Ambient Temperature
journal, April 2019
- I. Ciftci, Halil; G. Sierra, Raymond; Yoon, Chun
- International Journal of Molecular Sciences, Vol. 20, Issue 7
Design, Synthesis and Biological Evaluation of Pentacyclic Triterpene Derivatives: Optimization of Anti-ABL Kinase Activity
journal, September 2019
- I. Ciftci, Halil; O. Radwan, Mohamed; E. Ozturk, Safiye
- Molecules, Vol. 24, Issue 19
A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity
journal, January 2020
- Bayrak, Nilüfer; Yıldırım, Hatice; Yıldız, Mahmut
- Chemical Biology & Drug Design, Vol. 95, Issue 3