HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing-Reference-Cited by-同舟云学术

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

Published:2023-10-28 Issue:11 Volume:15 Page:2171
ISSN:1999-4915
Container-title:Viruses
language:en
Short-container-title:Viruses

Author:

Lyons Danielle E.¹,Kumar Priti²,Roan Nadia R.¹³^ORCID,Defechereux Patricia A.⁴,Feschotte Cedric⁵,Lange Ulrike C.⁶,Murthy Niren⁷⁸,Sameshima Pauline⁹^ORCID,Verdin Eric⁴¹⁰,Ake Julie A.¹¹,Parsons Matthew S.¹¹¹²¹³,Nath Avindra¹⁴,Gianella Sara¹⁵,Smith Davey M.¹⁵^ORCID,Kallas Esper G.¹⁶,Villa Thomas J.¹⁷¹⁸^ORCID,Strange Richard¹⁷,Mwesigwa Betty¹⁹^ORCID,Furler O’Brien Robert L.²⁰^ORCID,Nixon Douglas F.²⁰^ORCID,Ndhlovu Lishomwa C.²⁰^ORCID,Valente Susana T.²¹,Ott Melanie¹⁴

Affiliation:

1. Gladstone Institute of Virology, Gladstone Institutes, San Francisco, CA 94158, USA

2. Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA

3. Department of Urology, University of California San Francisco, San Francisco, CA 94158, USA

4. Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA

5. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA

6. Leibniz Institute of Virology, 20251 Hamburg, Germany

7. Department of Bioengineering, University of California, Berkeley, CA 94720, USA

8. Innovative Genomics Institute, Berkeley, CA 94720, USA

9. Faculty of Education, Lakehead University, Thunder Bay, ON P7B 5E1, Canada

10. Buck Institute for Research on Aging, Novato, CA 94945, USA

11. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

12. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA

13. Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand

14. Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20824, USA

15. Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA

16. Department of Infectious and Parasitic Diseases, University of Sao Paulo, São Paulo 04023-900, Brazil

17. HOPE Martin Delaney Collaboratory for HIV Cure Research Community Engagement Ambassador, Washinton, DC 20004, USA

18. National HIV & Aging Advocacy Network, Washington, DC 20004, USA

19. Research Department, Makerere University Walter Reed Project, Kampala P.O Box 7062, Uganda

20. Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA

21. Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA

Abstract

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

Funder

NIH

National Institutes of Health’s Office of the Director

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

Link

https://www.mdpi.com/1999-4915/15/11/2171/pdf

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