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

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Imle, Andrea, Kumberger, Peter, Schnellbächer, Nikolas D., Fehr, Jana, Carrillo-Bustamante, Paola, Ales, Janez, Schmidt, Philip, Ritter, Christian +7 more·2019·Nature Communications
DOI 10.1038/s41467-019-09879-3PMC PMC6514199
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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.

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  • A 3D environment limits infection by cell-free virions but promotes cell-associated HIV-1 transmission between T lymphocytes.

    “The tissue-like 3D culture systems greatly complement studies in vivo, and demonstrate that a 3D environment limits infection by cell-free virions, but promotes cell-associated HIV-1 transmission between T lymphocytes [132].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [132]

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Authors
Imle, A., Kumberger, P., Schnellbächer, N. D., Fehr, J., Carrillo-Bustamante, P., Ales, J., Schmidt, P., Ritter, C., Godinez, W. J., Müller, B., Rohr, K., Hamprecht, F. A., Schwarz, U. S., Graw, F., & Fackler, O. T.
Affiliations
  • University Hospital Heidelberg (DE)
  • Heidelberg University (DE)
  • Hasso Plattner Institute (DE)
  • German Cancer Research Center (DE)
Corresponding author
Fackler, Oliver T.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-05-13
Volume
10
Issue
1
Pages
2144-2144
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-09879-3
PMC
PMC6514199
OpenAlex
W2945993058
Cited by
76
References
3
Citations by year
2026: 3 · 2025: 5 · 2024: 11 · 2023: 7 · 2022: 23 · 2021: 12 · 2020: 12 · 2019: 3
FWCI
7.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • Deutsche Forschungsgemeinschaft (240245660, project 4, SFB1129, Project 6, Project 8)
  • Chica and Heinz Schaller Foundation
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mathematical and Theoretical Epidemiology and Ecology Models
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Keywords
3D cell culture, collagen scaffolds, CD4+ T cells, cell motility, cell density, virus diffusion, viral replication, infection dynamics
MeSH terms
Cell Movement, Cells, Cultured, Computer Simulation, Humans, Models, Biological, CD4-Positive T-Lymphocytes, HIV-1, Virus Physiological Phenomena, HEK293 Cells, Primary Cell Culture, Healthy Volunteers

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