Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane

Proceedings of the National Academy of Sciences of the United States of America
Zheng WangRobert F Siliciano

Abstract

The latent reservoir for HIV-1 in resting CD4+ T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses. Additional complications are that stimuli that drive T cell proliferation can also induce virus production from latently infected cells and productively infected cells have a short in vivo half-life. In this ex vivo study, we show that latently infected cells containing replication-competent HIV-1 can proliferate in response to T cell receptor agonists or cytokines that are known to induce homeostatic proliferation and that this can occur without virus production. Some cells that have proliferated in response to these stimuli can survive for 7 d while retaining the ability to produce virus. This finding supports the hypothesis that both antigen-driven and cytokine-induced proliferation may contribute to the stability of the latent reservoir. Sequencing of replication-competent proviruses isolated from patients at different time points confirmed the presence of expanded clones and demonstrated that while some clones harboring ...Continue Reading

References

Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·T W ChunA S Fauci
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T W ChunA S Fauci
Nov 30, 1999·JAMA : the Journal of the American Medical Association·G DornadulaR J Pomerantz
Jul 13, 2001·JAMA : the Journal of the American Medical Association·M HermankovaD Persaud
Jan 15, 2003·Journal of Virology·Deborah PersaudRobert F Siliciano
Apr 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·M C StrainJ K Wong
Apr 15, 2003·Journal of Virology·David C NickleJames I Mullins
Jun 17, 2003·Nature Immunology·Benedict SeddonRose Zamoyska
Jul 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Koichiro TamuraSudhir Kumar
Feb 17, 2005·JAMA : the Journal of the American Medical Association·Richard E NettlesRobert F Siliciano
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·J B DinosoF Maldarelli
Jun 23, 2009·Nature Medicine·Nicolas ChomontRafick-Pierre Sékaly
Jul 9, 2011·Nature Immunology·Jonathan Sprent, Charles D Surh
Oct 22, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Guillaume J BessonJohn W Mellors
Jul 28, 2012·Nature·Steven G Deeks
Jun 6, 2013·PLoS Pathogens·Gregory M LairdRobert F Siliciano
Jan 31, 2015·Cell·Lillian B CohnMichel C Nussenzweig
Apr 17, 2015·The Journal of Infectious Diseases·Amanda M CrooksNancie M Archin
Feb 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Francesco R SimonettiFrank Maldarelli
Mar 24, 2016·Molecular Biology and Evolution·Sudhir KumarKoichiro Tamura
Aug 9, 2016·Nature Medicine·Katherine M BrunerRobert F Siliciano
Nov 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Julio C C LorenziMichel C Nussenzweig

❮ Previous
Next ❯

Citations

May 31, 2018·Current Opinion in HIV and AIDS·Timothée Bruel, Olivier Schwartz
Aug 4, 2018·The Journal of Experimental Medicine·Yehuda Z CohenMichel C Nussenzweig
Sep 11, 2018·Cell Cycle·Dorota Piekna-Przybylska, Sanjay B Maggirwar
Dec 12, 2018·Current Opinion in HIV and AIDS·Katherine M Bruner, Lillian B Cohn
Jan 5, 2019·Current Opinion in HIV and AIDS·Chantelle L Ahlenstiel, Stuart G Turville
Feb 9, 2019·Journal of the International AIDS Society·R Brad Jones
Mar 19, 2019·Current Opinion in HIV and AIDS·Michael J Bale, Mary F Kearney
Jun 14, 2019·Journal of Virology·Rachel L MillerUNKNOWN ORCHID Study Group
Oct 11, 2019·Science Translational Medicine·Melissa-Rose AbrahamsRonald Swanstrom
Oct 4, 2019·Journal of Virology·Deanna A KulpaRafick-Pierre Sékaly
Feb 14, 2020·Journal of Virology·Germán G GornalusseFlorian Hladik
Aug 15, 2018·Antimicrobial Agents and Chemotherapy·Adam M SpivakVicente Planelles
Jan 9, 2020·Virology Journal·Runxia LiuYa-Chi Ho
Jun 4, 2020·PLoS Pathogens·Kelsie BrooksEric Hunter
Sep 12, 2019·Current HIV/AIDS Reports·Sara Rodríguez-MoraMayte Coiras
Apr 21, 2020·The Journal of Experimental Medicine·Pilar MendozaLillian B Cohn
Oct 5, 2018·JCI Insight·Amanda B MacedoAlberto Bosque
Nov 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ching-Lan LuMila Jankovic
Oct 17, 2019·Frontiers in Immunology·Talia M Mota, R Brad Jones
Aug 31, 2019·The Journal of Biological Chemistry·Alan N Engelman
Dec 20, 2019·Nature·Thumbi Ndung'uSteven G Deeks
Apr 23, 2020·Frontiers in Cellular and Infection Microbiology·Jordan ThomasGeorgios Pollakis
Jul 2, 2020·The Journal of Clinical Investigation·Caroline DufourNicolas Chomont
Apr 3, 2019·Nature Medicine·Marina CaskeyMichel C Nussenzweig
Feb 7, 2020·The Journal of Clinical Investigation·Yanqin RenR Brad Jones
Mar 7, 2020·Science Translational Medicine·Louise LeyreUNKNOWN RV254/SEARCH010, RV304/SEARCH013, SEARCH011 study groups
Jan 11, 2020·Frontiers in Microbiology·Shane D FalcinelliNancie M Archin
May 24, 2020·Viruses·Ashutosh ShuklaIván D'Orso
Sep 30, 2020·Current Pathobiology Reports·Adrianne L JennerMorgan Craig
Sep 28, 2018·Nature·Pilar MendozaMichel C Nussenzweig

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Francesco R SimonettiFrank Maldarelli
The Journal of Immunology : Official Journal of the American Association of Immunologists
Alexandra J MurrayRobert F Siliciano
Current Opinion in HIV and AIDS
Janet D Siliciano, Robert F Siliciano
© 2022 Meta ULC. All rights reserved