Quantitative Virology Research Group

Our research is bound to molecular barcodes, which are molecular tags, enabling the achievement of studies with resolution of single viruses. Together with in silico modeling and AI-based approaches, we investigate the mechanistic interplay between viruses, i.e. HIV-1 and SARS-CoV-2, and the host genome, with an emphasis on:

  • the investigation of latent HIV-1 reservoirs and stochastic HIV-1 transcription and
  • the identification of functional annotations of SARS-CoV-2 mutational signatures responsible for cross-species transmission.

Funders:

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).

Janusz Wiśniewski. Ph.D. Postdoc

I am a Bioinformatician with a biochemical past. I spent most of my career studying protein structure and interactions, both in academia and industry. My current research focuses on using language models with genomic and protein sequences of viruses, but my interests cover all applications of machine learning in life sciences.

Kamil Więcek. M.Sc. Process Engineer

I am a graduate of the University of Wrocław where I majored in medical biotechnology. Most of my scientific work so far has been focused on Immunology and inflammatory diseases. At present, I attempt to dissect the mechanistic interplay between the 3D genome organization and insert-specific HIV transcription.

Jędrzej Mazur, Intern, 03/2023-06/2023. Currently: Ph.D. student, Center for Structural Systems Biology, Liebniz Institute of Virology, Germany.

“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

2023

  • Thenin-Houssier, S., Machida, S., Jahan, C., Bonnet-Madin, J., Abbou, S., Chen, H.-C., Tesfaye, R., Cuvier, O., and Benkirane, M. 2023.
    POLE3 is a transcriptional repressor of unintegrated linear HIV-1 DNA required for efficient virus integration and escape from innate immune sensing.
    Sci. Adv. DOI:10.1126/sciadv.adh3642
  • Więcek, K., and Chen, H.-C. 2023.
    Understanding latent HIV-1 reservoirs through host genomics approaches.
    iScience DOI:10.1016/j.isci.2023.108342
  • Chen, H.-C. 2023.
    A systematic review of the barcoding strategy that contributes to COVID-19 diagnostics at a population level.
    Front. Mol. Biosci. DOI:10.3389/fmolb.2023.1141534
  • Chen, H.-C. 2023.
    The Dynamic Linkage between Provirus Integration Sites and the Host Functional Genome Property Alongside HIV-1 Infections Associated with Antiretroviral Therapy.
    Vaccines DOI:10.3390/vaccines11020402

2022

  • Chen, H.-C. 2022.
    Position matters – a discussion of HIV gene expression (中文主題名稱:原來擺對位置很重要 — 淺談人類免疫缺陷病毒的基因表現).
    Science Education Monthly (科學教育月刊) ISSN 1021-3708, 454, P25-32, DOI:10.6216/SEM

2021

  • 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. 2021.
    Author Correction: Spatially clustered loci with multiple enhancers are frequent targets of HIV-1.
    Nat. Commun. doi.org/10.1038/s41467-021-26471-w

2020

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

2019

  • 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. 2019.
    Spatially clustered loci with multiple enhancers are frequent targets of HIV-1.
    Nat. Commun. doi: 10.1038/s41467-019-12046-3

2018

  • 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. 2018.
    A new quinoline BRD4 inhibitor targets a distinct latent HIV-1 reservoir for re-activation from other ‘shock’ drugs.
    J Virol. doi: 10.1128/JVI.02056-17.
  • Chen, H.-C.*, E. Zorita, and G. Filion*. 2018.
    Using Barcoded HIV Ensembles (B-HIVE) for single provirus transcriptomics.
    Curr Protoc Mol Biol. doi: 10.1002/cpmb.56

2017

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

2015

  • Corrales, M., P. Cusco, D.R. Usmanova, H.-C. Chen, N.S. Bogatyreva, G.J. Filion, and D.N. Ivankov. 2015. Machine learning: how much does it tell about protein folding rates?
    PLoS One doi:10:e0143166.

2008

  • Chen, P.M., H.-C. Chen, C.T. Ho, C.J. Jung, H.T. Lien, J.Y. Chen, and J.S. Chia. 2008.
    The two-component system ScnRK of Streptococcus mutans affects hydrogen peroxide resistance and murine macrophage killing.
    Microbes and Infection doi:10:293-301.