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Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures

Author

Listed:
  • Andrea Imle

    (University Hospital Heidelberg
    European Molecular Biology Laboratory)

  • Peter Kumberger

    (Heidelberg University)

  • Nikolas D. Schnellbächer

    (Heidelberg University)

  • Jana Fehr

    (Heidelberg University
    Hasso-Plattner Institute)

  • Paola Carrillo-Bustamante

    (Heidelberg University
    Max-Planck Institute for Infection Biology)

  • Janez Ales

    (Heidelberg University)

  • Philip Schmidt

    (Heidelberg University)

  • Christian Ritter

    (Heidelberg University)

  • William J. Godinez

    (Heidelberg University)

  • Barbara Müller

    (University Hospital Heidelberg)

  • Karl Rohr

    (Heidelberg University)

  • Fred A. Hamprecht

    (Heidelberg University)

  • Ulrich S. Schwarz

    (Heidelberg University)

  • Frederik Graw

    (Heidelberg University)

  • Oliver T. Fackler

    (University Hospital Heidelberg
    Partner Site Heidelberg)

Abstract

Pathogens face varying microenvironments in vivo, but suitable experimental systems and analysis tools to dissect how three-dimensional (3D) tissue environments impact pathogen spread are lacking. Here we develop an Integrative method to Study Pathogen spread by Experiment and Computation within Tissue-like 3D cultures (INSPECT-3D), combining quantification of pathogen replication with imaging to study single-cell and cell population dynamics. We apply INSPECT-3D to analyze HIV-1 spread between primary human CD4 T-lymphocytes using collagen as tissue-like 3D-scaffold. Measurements of virus replication, infectivity, diffusion, cellular motility and interactions are combined by mathematical analyses into an integrated spatial infection model to estimate parameters governing HIV-1 spread. This reveals that environmental restrictions limit infection by cell-free virions but promote cell-associated HIV-1 transmission. Experimental validation identifies cell motility and density as essential determinants of efficacy and mode of HIV-1 spread in 3D. INSPECT-3D represents an adaptable method for quantitative time-resolved analyses of 3D pathogen spread.

Suggested Citation

  • Andrea Imle & Peter Kumberger & Nikolas D. Schnellbächer & Jana Fehr & Paola Carrillo-Bustamante & Janez Ales & Philip Schmidt & Christian Ritter & William J. Godinez & Barbara Müller & Karl Rohr & Fr, 2019. "Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09879-3
    DOI: 10.1038/s41467-019-09879-3
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    Cited by:

    1. Michael Gabel & Tobias Hohl & Andrea Imle & Oliver T Fackler & Frederik Graw, 2019. "FAMoS: A Flexible and dynamic Algorithm for Model Selection to analyse complex systems dynamics," PLOS Computational Biology, Public Library of Science, vol. 15(8), pages 1-23, August.
    2. Gustave Ronteix & Shreyansh Jain & Christelle Angely & Marine Cazaux & Roxana Khazen & Philippe Bousso & Charles N. Baroud, 2022. "High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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