HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy
Jenna B. Honeycutt,William O. Thayer,Caroline E. Baker,Ruy M. Ribeiro,Steven M. Lada,Youfang Cao,Rachel A. Cleary,Michael G. Hudgens,Douglas D. Richman,Douglas D. Richman,J. Victor Garcia +10 more
TLDR
Using humanized myeloid-only mice, it is demonstrated that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA.Abstract:
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA. No viral rebound was observed in the plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and no replication-competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (∼33%), a delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.read more
Citations
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Targeting the Latent Reservoir for HIV-1
TL;DR: Historical and recent paradigms in the HIV‐1 persistence field are discussed as well as novel immunologic and pharmacologic strategies for eliminating this reservoir, which is now the focus of an intense international research effort.
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Microglial Cells: The Main HIV-1 Reservoir in the Brain
Clémentine Wallet,Marco De Rovere,Jeanne Van Assche,Fadoua Daouad,Stéphane De Wit,Virginie Gautier,Patrick W. G. Mallon,Alessandro Marcello,Carine Van Lint,Olivier Rohr,Christian Schwartz +10 more
TL;DR: Better understandings of the specific molecular mechanisms of HIV-1 latency in microglial cells should help to design new molecules and new strategies preventing HAND and achieving HIV cure.
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Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Prasanta K. Dash,Rafal Kaminski,Ramona Bella,Hang Su,Saumi Mathews,Taha Mohseni Ahooyi,Chen Chen,Pietro Mancuso,Rahsan Sariyer,Pasquale Ferrante,Martina Donadoni,Jake A. Robinson,Brady Sillman,Zhiyi Lin,James R. Hilaire,Mary G. Banoub,Monalisha Elango,Nagsen Gautam,R. Lee Mosley,Larisa Y. Poluektova,JoEllyn M McMillan,Aditya N. Bade,Santhi Gorantla,Ilker Kudret Sariyer,Tricia H. Burdo,Won Bin Young,Shohreh Amini,Jennifer Gordon,Jeffrey M. Jacobson,Benson J Edagwa,Kamel Khalili,Howard E. Gendelman +31 more
TL;DR: This proof-of-concept study suggests that HIV-1 elimination is possible, and shows that sequential treatment with long-acting slow-effective release antiviral therapy and AAV9- based delivery of CRISPR-Cas9 results in undetectable levels of virus and integrated DNA in a subset of humanized HIV- 1 infected mice.
Journal ArticleDOI
HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy.
Yonatan Ganor,Fernando Real,Fernando Real,Fernando Real,Alexis Sennepin,Alexis Sennepin,Alexis Sennepin,Charles-Antoine Dutertre,Lisa Prevedel,Lin Xu,Lin Xu,Lin Xu,Daniela Tudor,Daniela Tudor,Daniela Tudor,Bénédicte Charmeteau,Bénédicte Charmeteau,Bénédicte Charmeteau,Anne Couëdel-Courteille,Anne Couëdel-Courteille,Anne Couëdel-Courteille,Sabrina Marion,Sabrina Marion,Sabrina Marion,Ali Redha Zenak,Ali Redha Zenak,Ali Redha Zenak,Jean Pierre Jourdain,Jean Pierre Jourdain,Jean Pierre Jourdain,Z Zhou,Z Zhou,Z Zhou,Alain Schmitt,Alain Schmitt,Alain Schmitt,Claude Capron,Eliseo A. Eugenin,Rémi Cheynier,Rémi Cheynier,Rémi Cheynier,Marc Revol,S. Cristofari,Anne Hosmalin,Anne Hosmalin,Anne Hosmalin,Morgane Bomsel,Morgane Bomsel,Morgane Bomsel +48 more
TL;DR: It is shown, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV- 1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethrals T cells.
Journal ArticleDOI
Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection
Lucy C K Bell,Mahdad Noursadeghi +1 more
TL;DR: The epidemiological associations between the two pathogens, selected interactions of each pathogen with the host and the current understanding of how they affect the pathogenesis of TB and HIV-1/AIDS in individuals with co-infections are described.
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