Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity


Journal

Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724

Informations de publication

Date de publication:
25 03 2021
Historique:
entrez: 4 2 2021
pubmed: 5 2 2021
medline: 5 2 2021
Statut: ppublish

Résumé

An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested. These GSK-3i's reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy (ART) in the absence of T cell activation, release of inflammatory cytokines, cell toxicity, or impaired effector function of cytotoxic T lymphocytes or NK cells. However, when administered

Identifiants

pubmed: 33536176
pii: JVI.02393-20
doi: 10.1128/JVI.02393-20
pmc: PMC8103695
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH112457
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127219
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI147777
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131374
Pays : United States
Organisme : NIH HHS
ID : S10 OD025002
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117901
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI083139
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150449
Pays : United States

Informations de copyright

Copyright © 2021 American Society for Microbiology.

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Auteurs

Andrea Gramatica (A)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Roland Schwarzer (R)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

William Brantley (W)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Benjamin Varco-Merth (B)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Hannah S Sperber (HS)

Vitalant Research Institute, San Francisco, California, USA.
Free University of Berlin, Institute of Biochemistry, Berlin, Germany.

Philip A Hull (PA)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.

Mauricio Montano (M)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.

Stephen A Migueles (SA)

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Danielle Rosenthal (D)

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Louise E Hogan (LE)

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Jeffrey R Johnson (JR)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.

Thomas A Packard (TA)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.

Zachary W Grimmett (ZW)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.

Eytan Herzig (E)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Emilie Besnard (E)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.

Michael Nekorchuk (M)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Feng Hsiao (F)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Urology, University of California, San Francisco, San Francisco, California, USA.

Steven G Deeks (SG)

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Michael Snape (M)

AMO Pharma Ltd., London, United Kingdom.

Bernard Kiernan (B)

AMO Pharma Ltd., London, United Kingdom.

Nadia R Roan (NR)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Urology, University of California, San Francisco, San Francisco, California, USA.

Jeffrey D Lifson (JD)

AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

Jacob D Estes (JD)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Louis J Picker (LJ)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

Eric Verdin (E)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA.

Nevan J Krogan (NJ)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA.

Timothy J Henrich (TJ)

Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Mark Connors (M)

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Melanie Ott (M)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA.

Satish K Pillai (SK)

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
Vitalant Research Institute, San Francisco, California, USA.

Afam A Okoye (AA)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA warner.greene@gladstone.ucsf.edu okoyea@ohsu.edu.

Warner C Greene (WC)

Gladstone Institute of Virology, Gladstone Institutes, San Francisco, California, USA warner.greene@gladstone.ucsf.edu okoyea@ohsu.edu.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA.

Classifications MeSH