Epigenetics of Infectious Diseases Research Group

Epigenetics of Infectious Diseases Research Group

We are curious about how the virus-host interaction evolves. We attempt to answer this big question using high-throughput and quantitative approaches and bioinformatics to dissect the molecular basis involved in their relationships. In principle, our studies focus on understanding (1) the molecular basis that contributes to viral pathogenesis, (2) what genome information appears to be essential after viral infections, and (3) how their relationship dynamically changes as time goes by. We presently focus on human immunodeficiency virus type 1 (HIV-1) and SARS-CoV-2.


Image credit: Heng-Chang Chen

Heng-Chang Chen, Dr. rer. nat., principal investigator

I am a molecular virologist and data scientist with over eight years of experience. I obtained a Ph.D. degree in Microbiology from the Humboldt University of Berlin (Berlin, Germany). Afterward, I joined the laboratory of Dr. Filion at the Centre for Genomic Regulation (Barcelona, Spain) and the laboratory of Dr. Benkirane at the Institute of Human Genetics (Montpellier, France) for postdoc research. During this period, I commenced my studies in HIV. In November 2022, I was appointed as the Junior Research Group Leader to head the new virology laboratory in the Center for Population Diagnostics in the Łukasiewicz Research Network – PORT Polish Center for Technology Development (Wrocław, Poland).

Kamil Więcek. M.Sc. Process Engineer

Martyna Uiściła. M.Sc. Process Engineer

“We question what makes HIV-1 transcriptionally silent”

HIV-1 DNA integration that enables the provirus to persist in a human reservoir for a long time is one of the critical characteristics of its life cycle. This biological phenomenon also highlights the unavoidable interaction between a provirus and the host genome. It has been known for many years that HIV-1 integration is not random; however, the purpose and the consequence of this selection of HIV-1 integration are presently not fully clear. One of the questions addressed by our team is to understand the consequence of this selection on HIV-1 pathogenesis. Specifically, we associate individual HIV-1 integration sites with corresponding sense- and antisense RNA transcription and investigate the role of single provirus transcriptomics in the establishment of HIV-1 latency.

Another question addressed here is to comprehend the evolution of the configuration of HIV-1 reservoirs. We have shown that different and unique immunologic signatures can be enriched by intact proviruses-targeted genes retrieved from HIV-1-infected individuals alongside infections associated with ART, suggesting that most likely the configuration of a HIV-1 reservoir remains dynamic after HIV-1 infections. We thus hypothesize that HIV-1 integration frequency might be used as a surrogate for gene sets, which may define specific immune cell types and proinflammatory soluble factors during HIV-1 infection. To verify this hypothesis, we use the in vivo model system to track and visualize the alteration of the landscapes of proviruses in different reservoir cells over time and elucidate the mechanistic interplay between gene sets targeted by wild-type HIV-1 and the functional genome property.

Figure 1. Schematic representation of our tactical approaches to study the interaction between HIV-1 integration and the host genome. We investigate the role of insert-specific HIV-1 transcription coupled with the epigenomic features surrounding the site of HIV-1 integration, the 3D genome, and the functional property of the whole genome. Image credit: Heng-Chang Chen

“We question what makes zoonotic viruses infect humans”

Nearly two-thirds of emerging infectious diseases that affect humans have their origins in animal reservoirs. To date, although evolutionary constraints, rendering some zoonotic viruses adaptive to humans remain unclear, genetic mutations that result in new variants of the viruses provide a window of opportunity for viral host jumps. In this respect, knowing when and how such mutations occur becomes essential to understand how constraints determine the fate of the virus, especially over an evolutionary timescale. In practice, we implement a high-throughput evolutionary strategy to probe constraints crucial for cross-species transmission in SARS-CoV-2 (Figure 2).

Figure 2. Schematic representation of our conceptual thought in studying the functional consequence of variants of SARS-CoV-2. We probe the potential mutations required for SARS-CoV-2 cross-species transmission using a high-throughput in vitro system. Image credit: Heng-Chang Chen


  • Chen, H.-C.
    The dynamic Linkage between Provirus Integration Sites and the Host Functional Genome Property Alongside HIV-1 Infectious Associated with Antiretroviral Therapy.
    Vaccines., 2023, DOI: 10.3390/vaccines11020402


  • H.-C. Chen
    The dynamic linkage between intact provirus integration sites and the host functional genome property alongside HIV-1 infections associated with antiretroviral therapy.
    BioRxiv., 2022, DOI: 10.1101/2022.12.02.518849


  • Vansant*, G., H.-C. Chen*, E. Zorita, Trejbalová, K., Miklík, D., G. Filion, and Z. Debyser
    The chromatin landscape at the HIV-1 provirus integration site determines viral expression.
    Nucleic Acids Res., 2020, DOI: 10.1093/nar/gkaa536 (*Shared first authors)
  • Machida, S., D. Depierre, H.-C. Chen, S. Houssier, G. Petitjean, C. Doyen, M. Takaku, O. Cuvier and M. Benkirane
    Exploring histone loading on HIV DNA reveals a dynamic nucleosome positioning between unintegrated and integrated viral genome.
    PNAS, 2020, DOI: 10.1073/pnas.1913754117


  • Lucic, B.*, H.-C. Chen*, M. Kuzman*, E. Zorita*, J. Wegner, V. Minneker, W. Wang, R. Fronza, M. Schmidt, and R. Stadhouders, V. Roukos, K. Vlahovicek, G. Filion and M. Lusic
    Spatially clustered loci with multiple enhancers are frequent targets of HIV-1.
    Nat. Commun, 2020, DOI: 10.1038/s41467-019-12046-3 (*Shared first authors)


  • Abner, E., M. Stoszko, L. Zeng, H.-C. Chen, A. Izquierdo-Bouldstridge, T. Konuma, E. Zorita, E. Fanunza, Q. Zhang, T. Mahmoudi, M.-M. Zhou, G. Filion, and A. Jordan
    A new quinoline BRD4 inhibitor targets a distinct latent HIV-1 reservoir for re-activation from other ‘shock’ drugs.
    J Virol., 2018, DOI: 10.1128/JVI.02056-17
  • Chen, H.-C.*, E. Zorita, and G. Filion*
    Using Barcoded HIV Ensembles (B-HIVE) for single provirus transcriptomics.
    Curr Protoc Mol Biol., 2018, DOI: 10.1002/cpmb.56 (*Corresponding authorship)


  • Chen, H.-C., J.P. Martinez, E. Zorita, A. Meyerhans, and G. Filion
    Position effects influence HIV latency reversal.
    Nat Struct Mol Biol., 2017, DOI: 10.1038/nsmb.3328