Evaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity Ex Vivo and In Vivo

Author:

Gramatica Andrea12,Schwarzer Roland12,Brantley William3,Varco-Merth Benjamin3,Sperber Hannah S.45,Hull Philip A.1,Montano Mauricio1,Migueles Stephen A.6,Rosenthal Danielle6,Hogan Louise E.2,Johnson Jeffrey R.17,Packard Thomas A.1,Grimmett Zachary W.1,Herzig Eytan12,Besnard Emilie1,Nekorchuk Michael3,Hsiao Feng18,Deeks Steven G.2,Snape Michael9,Kiernan Bernard9,Roan Nadia R.18,Lifson Jeffrey D.10,Estes Jacob D.3,Picker Louis J.3,Verdin Eric1211,Krogan Nevan J.17,Henrich Timothy J.2,Connors Mark6,Ott Melanie1211,Pillai Satish K.124,Okoye Afam A.3,Greene Warner C.1211ORCID

Affiliation:

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

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

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

4. Vitalant Research Institute, San Francisco, California, USA

5. Free University of Berlin, Institute of Biochemistry, Berlin, Germany

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

7. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, USA

8. Department of Urology, University of California, San Francisco, San Francisco, California, USA

9. AMO Pharma Ltd., London, United Kingdom

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

11. Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USA

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

Abstract

If combined with immune therapeutics, latency-reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8 + T and NK cell cytotoxic effector functions.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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