Article
Immunology
Rajesh T. Gandhi, Joshua C. Cyktor, Ronald J. Bosch, Hanna Mar, Gregory M. Laird, Albine Martin, Ann C. Collier, Sharon A. Riddler, Bernard J. Macatangay, Charles R. Rinaldo, Joseph J. Eron, Janet D. Siliciano, Deborah K. McMahon, John W. Mellors
Summary: Intact, replication-competent proviruses are selectively lost over time during suppressive ART, while defective provirus levels remain stable. The proportion of intact proviruses within the total HIV-1 DNA reservoir decreases over time on ART. Levels of intact proviruses on ART are correlated with total HIV-1 DNA and residual plasma viremia, but not with markers of inflammation or immune activation.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Virology
John M. Coffin, Stephen H. Hughes
Summary: HIV infection forms a latent reservoir during ART treatment, with most cells being large clones rather than the traditional resting cells. These expanding or destined-to-expand cells are primarily antigen-driven, with a majority carrying defective proviruses but some carrying intact infectious proviruses. While most proviruses remain transcriptionally silent, a small fraction can produce low levels of infectious virus.
Article
Biochemistry & Molecular Biology
Yingke Tang, Ryan T. Behrens, Corine St Gelais, Siqi Wu, Saravanan Vivekanandan, Ehud Razin, Pengfei Fang, Li Wu, Nathan Sherer, Karin Musier-Forsyth
Summary: Human lysyl-tRNA synthetase (LysRS) is re-localized from cytoplasm to nucleus in HIV-1 infected cells through phosphorylation. Phosphorylation promotes HIV-1 transcription, and nuclear pS207-LysRS generates Ap4A, which also activates HIV-1 transcription. Additionally, MSC-derived peptide stabilizes LysRS MSC binding and inhibits HIV-1 replication.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Infectious Diseases
Fengting Wu, Francesco R. Simonetti
Summary: The study of persistent viremia in HIV-1 reservoir during antiretroviral therapy has implications for clinical care and HIV-1 remission research, shedding light on virus-host interactions and challenges faced by individuals on ART.
CURRENT HIV/AIDS REPORTS
(2023)
Article
Microbiology
Jeffrey Kuniholm, Elise Armstrong, Brandy Bernabe, Carolyn Coote, Anna Berenson, Samantha D. Patalano, Alex Olson, Xianbao He, Nina H. Lin, Juan I. Fuxman Bass, Andrew J. Henderson
Summary: HIV-1 establishes a persistent proviral reservoir by integrating into the genome of host cells, with over 90% of integrated HIV genomes found to be defective. Resting CD4+ T cells and monocyte-derived macrophages (MDMs) were observed to bias towards generating defective HIV-1 proviruses. The study also identified aberrant transcripts lacking 5' untranslated regions, indicating a mechanistic insight into how defective HIV-1 proviruses are persistently expressed.
Article
Medicine, Research & Experimental
Gabriel Duette, Bonnie Hiener, Hannah Morgan, Fernando G. Mazur, Vennila Mathivanan, Bethany A. Horsburgh, Katie Fisher, Orion Tong, Eunok Lee, Haelee Ahn, Ansari Shaik, Remi Fromentin, Rebecca Hoh, Charline Bacchus-Souffan, Najla Nasr, Anthony L. Cunningham, Peter W. Hunt, Nicolas Chomont, Stuart G. Turville, Steven G. Deeks, Anthony D. Kelleher, Timothy E. Schlub, Sarah Palmer
Summary: Through studying CD4(+) T cells of HIV-1 patients, the importance of effector memory T cells in the persistence of HIV-1 has been identified, and Nef has been suggested as a potential therapeutic target.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Shelby Winans, Hyun Jae Yu, Kenia de los Santos, Gary Z. Wang, Vineet N. KewalRamani, Stephen P. Goff
Summary: HIV-1 integration sites are biased towards actively transcribed genes, but a mutation can redirect viral DNA integration to the centromeres of host chromosomes, potentially affecting HIV latency.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Nathan L. Board, Milica Moskovljevic, Fengting Wu, Robert F. Siliciano, Janet D. Siliciano
Summary: Current strategies for HIV-1 cure have not been successful in eliminating the latent reservoir, but engaging the immunology of dendritic cells and natural killer cells holds potential for achieving HIV-1 cure.
NATURE REVIEWS IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Natalie N. Kinloch, Yanqin Ren, Winiffer D. Conce Alberto, Winnie Dong, Pragya Khadka, Szu Han Huang, Talia M. Mota, Andrew Wilson, Aniqa Shahid, Don Kirkby, Marianne Harris, Colin Kovacs, Erika Benko, Mario A. Ostrowski, Perla M. Del Rio Estrada, Avery Wimpelberg, Christopher Cannon, W. David Hardy, Lynsay MacLaren, Harris Goldstein, Chanson J. Brumme, Guinevere Q. Lee, Rebecca M. Lynch, Zabrina L. Brumme, R. Brad Jones
Summary: The Intact Proviral DNA Assay quantifies intact HIV reservoirs but faces a 28% failure rate due to HIV-1 polymorphism. Within-host HIV-1 diversity poses a challenge to the accuracy of IPDA measurements.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Jeffrey C. Umotoy, Steven W. de Taeye
Summary: Despite the improvements in life expectancy for people living with HIV-1 through antiretroviral therapy, a cure for HIV/AIDS remains elusive. The emergence of drug resistance has led to increased treatment failures, highlighting the need for novel strategies for HIV-1 cure. Antibody conjugates (ACs) show promise in addressing limitations of current ART, reducing off-target effects, toxicity, and production costs, and are being explored for their potential in HIV-1 cure.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Infectious Diseases
Marc Wirden, Romain Palich, Basma Abdi, Marc Antoine Valantin, Roland Tubiana, Luminita Schneider, Sophie Seang, Antoine Faycal, Baptiste Sellem, Christine Katlama, Vincent Calvez, Anne-Genevieve Marcelin
Summary: This study describes the impact of switching from COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) to the Cobas 6800 system (C6800) on HIV-1 RNA quantification. The results show that C6800 can detect low-level viraemia that was not detected by CAP/CTM, resulting in more patients being found to have higher viral loads.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Immunology
Fernanda A. Ferreira, Qianjing He, Stephanie Banning, Olivia Roberts-Sano, Olivia Wilkins, Daniel R. Kuritzkes, Athe Tsibris
Summary: This study investigated the effects of different analysis pipelines on the characterization of HIV-1 proviral sequences, finding that the choice of pipeline can bias the classification of defective sequences. It was observed that specific pipelines may lead to an overestimation of intact proviral sequences, highlighting the importance of developing a consensus elimination pipeline for improved cross-research group comparisons.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2021)
Article
Virology
Maria Abad-Fernandez, Francisco J. Hernandez-Walias, Maria J. Ruiz de Leon, Maria J. Vivancos, Maria J. Perez-Elias, Ana Moreno, Jose L. Casado, Carmen Quereda, Fernando Dronda, Santiago Moreno, Alejandro Vallejo
Summary: Individuals coinfected with HIV-1 and HTLV-2 exhibit slower CD4(+) T cell depletion, natural control of HIV-1, and lower mortality rates. The infection may benefit by increasing CD8(+) T cell-mediated HIV-1 inhibition and cytolytic factors, leading to lower HIV-1 viral load.
Article
Biochemical Research Methods
Willem van Snippenberg, David Gleerup, Sofie Rutsaert, Linos Vandekerckhove, Ward De Spiegelaere, Wim Trypsteen
Summary: The development of an HIV-1 cure is hindered by the presence of a persistent reservoir of intact proviruses. It is crucial to accurately evaluate and quantify these proviruses to determine the efficacy of HIV-1 cure strategies. This study presents two triplex digital PCR assays and validates their performance in detecting HIV-1 reservoirs.
Article
Virology
Valerie F. Boltz, Cristina Ceriani, Jason W. Rausch, Wei Shao, Michael J. Bale, Brandon F. Keele, Rebecca Hoh, Jeffrey M. Milush, Steve G. Deeks, Frank Maldarelli, Mary F. Kearney, John M. Coffin
Summary: Researchers investigated the relationship between latent HIV-1 infection and genome methylation, finding no support for the proposition that latent HIV infection is associated with methylation of the HIV 5' LTR promoter.