Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures
Imle A, Kumberger P, Schnellbaecher ND, Fehr J, Carrillo-Bustamante P, Ales J, Schmidt P, Ritter C, Godinez WJ, Mueller B, Rohr K, Hamprecht FA, Schwarz US, Graw F, Fackler OT (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 10
Article Number: 2144
Journal Issue: 1
DOI: 10.1038/s41467-019-09879-3
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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Germany (DE)How to cite
APA:
Imle, A., Kumberger, P., Schnellbaecher, N.D., Fehr, J., Carrillo-Bustamante, P., Ales, J.,... Fackler, O.T. (2019). Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09879-3
MLA:
Imle, Andrea, et al. "Experimental and computational analyses reveal that environmental restrictions shape HIV-1 spread in 3D cultures." Nature Communications 10.1 (2019).
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