Article
Microbiology
Julie Janssens, Flore De Wit, Nagma Parveen, Zeger Debyser
Summary: Current antiretroviral treatment is unable to cure HIV-1 infection, as the virus can hide in cellular reservoirs and rebound after therapy is discontinued. This study investigates the impact of LEDGINs on the location, transcription, and reactivation of HIV-1. The results suggest that LEDGIN-mediated retargeting can hinder viral transcription and lead to an enrichment of provirus in deep latency. These findings have implications for the development of functional cure strategies for HIV-1.
Article
Biochemistry & Molecular Biology
Gregory J. Bedwell, Alan N. Engelman
Summary: Integration of retroviral reverse transcripts into the chromatin of host cells is crucial for virus replication, with HIV-1 efficiently infecting interphase cells and targeting specific chromosomal sites for integration. The interactions between viral and host factors, as well as the nuclear landscape, play key roles in facilitating HIV-1 integration and influencing the establishment of active versus latent virus infection.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Microbiology
Julie Janssens, Anne Bruggemans, Frauke Christ, Zeger Debyser
Summary: This review discusses strategies for HIV-1 remission or a functional cure, emphasizing the importance of silencing the virus rather than eradicating it. It explores key factors controlling HIV-1 expression and silencing mechanisms, including the impact of integration site selection and the role of LEDGF/p75.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Virology
Fang Lu, Urvi Zankharia, Olga Vladimirova, Yanjie Yi, Ronald G. Collman, Paul M. Lieberman
Summary: HIV-infected macrophages have a unique epigenetic control pattern, with viral genomes maintained in a noncanonical bivalent state. These findings may contribute to the discovery of new mechanisms for controlling chronic HIV expression in infected macrophages.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Hannah O. Ajoge, Tyler M. Renner, Kasandra Belanger, Matthew Greig, Samar Dankar, Hinissan P. Kohio, Macon D. Coleman, Emmanuel Ndashimye, Eric J. Arts, Marc-Andre Langlois, Stephen D. Barr
Summary: APOBEC3 (A3) proteins, a type of host-encoded deoxycytidine deaminase, play a crucial role in providing innate immune defense against retroviral infections such as HIV-1. This study reveals that A3 proteins impact the integration site selection of HIV-1 proviral DNA, leading to integration into transcriptionally inactive regions of the genome. This finding provides valuable insights into the evolution and infection mechanisms of HIV-1.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Ryan Yucha, Morgan L. Litchford, Carolyn S. Fish, Zak A. Yaffe, Barbra A. Richardson, Elizabeth Maleche-Obimbo, Grace John-Stewart, Dalton Wamalwa, Julie Overbaugh, Dara A. Lehman
Summary: This study investigated the levels of HIV provirus in a cohort of Kenyan children and found that specific immune factors prior to ART initiation were related to the levels of HIV proviruses. These findings are important for understanding the formation of the HIV reservoir and developing cure strategies.
Article
Cell Biology
Guoxin Liang, Yang He, Li Zhao, Jiayue Ouyang, Wenqing Geng, Xiaowei Zhang, Xiaoxu Han, Yongjun Jiang, Haibo Ding, Ying Xiong, Jinxiu Dong, Mei Liu, Hong Shang
Summary: This study identifies CTNNBL1 protein as a potent inhibitor of HIV-1 integration by associating with viral-encoded integrase (IN) and its cofactor. CTNNBL1 overexpression blocks HIV-1 integration and inhibits viral replication, while its depletion upregulates HIV-1 integration into target cells. CTNNBL1 expression is downregulated in activated CD4(+) T cells, and its depletion facilitates HIV-1 integration in resting CD4(+) T cells.
Article
Biology
Yuheng Huang, Harsh Shukla, Yuh Chwen G. Lee
Summary: Transposable elements (TEs) are selfish genetic parasites that increase their copy number at the expense of host fitness. The abundance of TEs differs greatly between species, and this study explores the role of TE-mediated local enrichment of repressive marks in determining genomic TE abundance. The results show that the TE-mediated effect varies across and even within species, and the transcription of neighboring genes can impact this spreading. This multi-species analysis highlights the importance of host chromatin landscapes in shaping genome evolution through the epigenetic effects of TEs.
Article
Cell Biology
Hong-Tao Li, H. Josh Jang, Krizia Rohena-Rivera, Minmin Liu, Hemant Gujar, Justin Kulchycki, Shuqing Zhao, Sandrin Billet, Xinyi Zhou, Daniel J. Weisenberger, Inderbir Gill, Peter A. Jones, Neil A. Bhowmick, Gangning Liang
Summary: Tumors with mutations in chromatin regulators, such as SETD2, are sensitive to DNA hypomethylating agent DAC therapy, which activates viral mimicry responses through mis-splicing events. Comprehensive epigenomic analysis reveals that H3K9me3 deposition across intronic TEs contributes to increased mis-splicing rates. SETD2-deficient kidney cancers are prone to mis-splicing, and DAC treatment can exacerbate this effect to enhance viral mimicry activation and synergize with immuno-therapy approaches.
Article
Biochemistry & Molecular Biology
Jack A. Collora, Ya-Chi Ho
Summary: HIV-1 integration introduces ectopic transcription factor binding sites into host chromatin, serving as an ectopic enhancer that recruits transcription factors, increases chromatin accessibility, changes 3D chromatin interactions, and enhances gene expression.
Article
Virology
Nicklas Sapp, Nathaniel Burge, Khan Cox, Prem Prakash, Muthukumar Balasubramaniam, Santosh Thapa, Devin Christensen, Min Li, Jared Linderberger, Mamuka Kvaratskhelia, Jui Pandhare, Robert Craigie, Michael G. Poirier, Chandravanu Dash
Summary: HIV-1 infection depends on the integration of viral DNA into host chromosomes. This study reveals the preference for HIV-1 integration into open chromatin and the role of H3K36me3 histone modification in integration. The findings also highlight distinct mechanisms used by the preintegration complex (PIC) and intasomes for integration.
JOURNAL OF VIROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jote T. Bulcha, Yi Wang, Hong Ma, Phillip W. L. Tai, Guangping Gao
Summary: The field of gene therapy has made significant progress in combating human diseases and providing hope to patients and families with limited treatment options, but it has also faced setbacks. Viral-based vectors have played a crucial role in developing powerful drug platforms, but challenges still limit their full potential.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Virology
Lele Zhao, Chris Wymant, Francois Blanquart, Tanya Golubchik, Astrid Gall, Margreet Bakker, Daniela Bezemer, Matthew Hall, Swee Hoe Ong, Jan Albert, Norbert Bannert, Jacques Fellay, M. Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F. Gunthard, Pia Kivela, Roger D. Kouyos, Oliver Laeyendecker, Laurence Meyer, Kholoud Porter, Ard van Sighem, Marc van der Valk, Ben Berkhout, Paul Kellam, Marion Cornelissen, Peter Reiss, Christophe Fraser, Luca Ferretti
Summary: This study investigates the relationship between viral load and transmission fitness in HIV-1. The results suggest that higher set-point viral load is associated with increased infectiousness and transmission fitness. This finding has implications for understanding the evolution and spread of HIV-1.
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
Cell Biology
Mona Rheinberger, Ana Luisa Costa, Martin Kampmann, Dunja Glavas, Iart Luca Shytaj, Sheetal Sreeram, Carlotta Penzo, Nadine Tibroni, Yoelvis Garcia-Mesa, Konstantin Leskov, Oliver T. Fackler, Kristian Vlahovicek, Jonathan Karn, Bojana Lucic, Carl Herrmann, Marina Lusic
Summary: HIV-1 integrates into the host chromatin in a hierarchically organized manner and persists in latent reservoirs. This study examines the integration sites of HIV-1 in a microglia cell model and their association with chromatin and gene expression signatures. It also highlights the importance of host genome organization, specifically the presence of CTCF and topologically associated domain boundaries, in HIV-1 infection.
Article
Biotechnology & Applied Microbiology
Alessandro Canella, Siska Van Belle, Tine Brouns, Giovanni Nigita, Marianne S. Carlon, Frauke Christ, Zeger Debyser
Summary: LEDGF/p75 plays a crucial role in leukemogenesis in MLL, as well as in cancer survival, stem cell renewal, and activation of nuclear super enhancers.
CANCER GENE THERAPY
(2022)
Article
Multidisciplinary Sciences
Moritz Bauer, Enrique Vidal, Eduard Zorita, Nil Uresin, Stefan F. Pinter, Guillaume J. Filion, Bernhard Payer
Summary: The study reveals the presence of A/B-like compartments on the inactive X chromosome, guiding TAD formation independently of transcription during X-reactivation. The formation of TADs and transcriptional reactivation are shown to be causally independent during X-reactivation, with Xist identified as a common factor.
NATURE COMMUNICATIONS
(2021)
Correction
Multidisciplinary Sciences
Bojana Lucic, Heng-Chang Chen, Maja Kuzman, Eduard Zorita, Julia Wegner, Vera Minneker, Wei Wang, Raffaele Fronza, Stefanie Laufs, Manfred Schmidt, Ralph Stadhouders, Vassilis Roukos, Kristian Vlahovicek, Guillaume J. Filion, Marina Lusic
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Manisha Kabi, Guillaume J. Filion
Summary: Some viruses hide in their host's genome by integrating as a provirus. This study reviews the mechanisms by which chromatin silences integrated viruses and proposes that DNA repair may play a role in flagging these viruses as "non-self" shortly after integration.
TRENDS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aline Acke, Siska Van Belle, Boris Louis, Raffaele Vitale, Susana Rocha, Thierry Voet, Zeger Debyser, Johan Hofkens
Summary: Interactions between epigenetic readers and histone modifications are crucial in gene expression regulation. We have developed a method called Expansion Microscopy for Epigenetics (ExEpi) that preserves spatial information and improves resolution, allowing the study of epigenetic interactions and drug discovery.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Julie Janssens, Flore De Wit, Nagma Parveen, Zeger Debyser
Summary: Current antiretroviral treatment is unable to cure HIV-1 infection, as the virus can hide in cellular reservoirs and rebound after therapy is discontinued. This study investigates the impact of LEDGINs on the location, transcription, and reactivation of HIV-1. The results suggest that LEDGIN-mediated retargeting can hinder viral transcription and lead to an enrichment of provirus in deep latency. These findings have implications for the development of functional cure strategies for HIV-1.
Correction
Computer Science, Artificial Intelligence
Guillaume J. Filion
Article
Biochemistry & Molecular Biology
Moritz Bauer, Bernhard Payer, Guillaume J. Filion
Summary: The spatial organization of genomes is closely related to transcription, and understanding whether gene activity is a cause or consequence of genome folding is an important research objective. Recent studies on the structural changes associated with X-chromosome inactivation and reactivation shed light on this cause-consequence relationship between genome conformation and transcription.
Review
Virology
Eline Pellaers, Anayat Bhat, Frauke Christ, Zeger Debyser
Summary: To complete replication, retroviruses integrate their RNA genome into a host chromosome by selecting specific integration sites. These integration sites play important roles in retroviral replication, oncogenesis, and latency. This review summarizes the mechanisms underlying integration site selection in gammaretrovirus MLV and lentivirus HIV-1 and discusses how understanding these mechanisms can contribute to the development of safer viral vectors for gene therapy and potentially lead to a cure for HIV-1 infection.
Article
Immunology
Heng-Chang Chen
Summary: The study investigates the functional interaction between HIV-1 integration and the activation of host biological pathways. The results indicate that specific immune cells and proinflammatory soluble factors are associated with HIV-1 infections during antiretroviral therapy. Additionally, enriched KEGG pathways are related to cancer, immune system, infectious disease viral, and signal transduction.
Article
Biochemistry & Molecular Biology
Dalibor Miklik, Jiri Grim, Daniel Elleder, Jiri Hejnar
Summary: This study presents a novel statistical approach using multicomponent mixture models to investigate retroviral integration site sequences. It reveals the existence of both palindromic and nonpalindromic submotifs in these sequences. The weak palindromic motifs are formed by site-specific submotifs restricted to a few positions proximal to the site of integration. Furthermore, HIV-1-favored palindromic sequences are identified in Alu repeats.
Review
Biochemistry & Molecular Biology
Heng-Chang Chen
Summary: The outbreak of SARS-CoV-2 has highlighted the importance of population-level viral diagnostics to control the spread of the disease. Barcoding technology, which allows for high-throughput testing of multiple samples simultaneously, has been used for molecular diagnostics for SARS-CoV-2 infections. This technology can also be combined with other biotechnologies to study the virus at a single molecule level.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Kamil Wiecek, Heng-Chang Chen
Summary: The genetic integrity of HIV-1 proviruses is crucial for curing infection, but intact proviruses are not common in HIV-1 reservoirs. A recent concept of a revised HIV-1 deeply latent reservoir suggests that the establishment of HIV-1 reservoirs is influenced by immune-mediated selection, resulting in genetically intact proviruses that are best suited to evade clearance.
Correction
Public, Environmental & Occupational Health
Patrice Cani, Peter Clarys, Antoine Clinquart, Stefaan De Henauw, Nathalie Delzenne, Peter Deriemaeker, Caroline Douny, Isabelle Guelinckx, Inge Huybrechts, Lieven Huybregts, Patrick Kolsteren, Carl Lachat, Isabelle Laquiere, Yvan Larondelle, Jef Leroy, Guy Manghuin-Rogister, Christophe Matthys, Patrick Mullie, Jean Neve, Marie-Louise Scippo, Isabelle Sioen, Anne-Marie Remaut, John Van Camp, Stefanie Vandevijvere, Margareta Vansant
ARCHIVES OF PUBLIC HEALTH
(2023)
Article
Biotechnology & Applied Microbiology
Victoria O. Pokusaeva, Aranzazu Rosado Diez, Lorena Espinar, Albert Torello Perez, Guillaume J. Filion
Summary: The processing of double-strand breaks has a major influence on the repair of mismatches during single-strand annealing, with a bias in favor of the strand with the longest 3' flap.