Silence
is a Behaviour
Quantitative Virology Research Group
RESEARCH PROJECTS
2023-2027: Role of HIV antisense transcripts in the establishment of latency: genome-wide map antisense RNAs to understand how they regulate HIV transcription
(Principal Investigator: H.C. Chen, Łukasiewicz Research Network - PORT, Wrocław, Poland)
This project is funded by National Science Centre Poland (NCN) SONATA BIS 12 (ID: 563746; Reg. No: DEC-2022/46/E/NZ6/00022; 3,724,878 PLN).
Publications from this project:
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Więcek, K., and Chen, H.-C. iScience 2023 DOI:10.1016/j.isci.2023.108342
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Wiśniewski, et al. iScience 2024 DOI:10.1016/j.isci.2024.111222
2019-2022: Characterization of the role of unintegrated HIV DNA
(Supervisor: M. Benkirane, Institut de Génétique Humaine, Montpellier, France)
We investigated the role of linear unintegrated HIV DNA, which establishes a repressive chromatin structure to impose transcriptional silencing. We observed a nucleosome covering the DNA hypersensitive site, NucDHS, which is found within unintegrated viral DNA. The presence of NucDHS within the promoter-proximal region at the HIV 5’ long terminal repeat interferes with RNAPII recruitment. Furthermore, using the proteomics of isolated chromatin segments method, we identified the host factor POLE3 that functions by maintaining the viral genome in a chromatin-repressive state as a transcriptional repressor of linear unintegrated HIV DNA.
Publications from this project:
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Machida, S., et al. PNAS 2020 DOI:10.1073/pnas.1913754117
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Thenin-Houssier, S. et al. Sci. Adv. DOI:10.1126/sciadv.adh3642
2017-2020: The chromatin landscape at the HIV-1 provirus integration site determines viral expression
(Collaboration with the lab of Z. Debyser, KU Leuven, Leuven, Flanders, Belgium)
We prove that LEDGINs, which are small molecule inhibitors of HIV integrase-LEDGF/p75 interaction enable to retarget HIV out of gene-dense and actively transcribed regions and consequently reduce viral RNA expression and increase the proportion of silent provirus.
Publications from this project:
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Vansant, G., H.-C. Chen, et al. Nucleic Acids Res 2020 DOI:10.1093/nar/gkaa536
2015-2018: The selection of HIV integration sites in the 3D genome
(Supervisor: G. Filion, Centre de Regulació Genòmica, Barcelona, Spain)
We show the bias of HIV integration in the 3D genomic architecture: viruses tend to integrate in spatial proximity of super-enhancers in primary CD4+ T cells and in T cell cultures in vitro.
Publications from this project:
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Lucic, B., and Chen, H.-C. Nat Commun 2021 DOI:10.1038/s41467-021-26471-w
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Lucic, B., and Chen, H.-C. Nat Commun 2019 DOI:10.1038/s41467-019-12046-3
2013-2016: Position effects influence HIV latency reversal
(Supervisor: G. Filion, Centre de Regulació Genòmica, Barcelona, Spain)
We successfully proved that HIV transcription is influenced by the local genomic context: viruses that integrate close to endogenous enhancers display a higher transcriptional level than those integrating far from enhancers.
Publications from this project:
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Chen, H.-C. et al. Curr Protoc Mol Biol. 2018 DOI:10.1002/cpmb.56
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Chen, H.-C. et al. Nat Struct Mol Biol. 2017 DOI:10.1038/nsmb.3328
2008-2011: Identification and characterization of a novel Salmonella gene product STM0029
(Supervisor: L.H. Wieler & K. Tedin, Humboldt-Universität zu Berlin, Berlin, Germany)
We reveal the importance of a novel Salmonella gene product STM0029 which contributes to the resistance to host antimicrobial peptide killing (DOI: 10.18452/16658).
2004-2006: Characterization of a putative function of the two-component system ScnRK in Streptococcus mutans
(Supervisor: J.S. Chia, National Taiwan University, Taipei, Taiwan)
We identify the function of S. mutans two-component system ScnRK involved in the resistance of hydrogen peroxide and murine macrophage killing.
Publications from this project:
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Chen, P.M., and Chen, H.-C. et al. Microbes and Infection 2008 DOI:10.1016/j.micinf.2007.12.006