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The spread of pathogens such as the human immunodeficiency virus (HIV) is often studied in a test tube, ie in two-dimensional cell cultures, even if it hardly reflects the much more complex conditions of the human body. human body. An interdisciplinary team of scientists from the University of Heidelberg used innovative cell culture systems, quantitative image badysis and computer simulations. She explored how HIV spreads in three-dimensional tissue-like environments. The results of the researchers show that the structure of the tissue forces the virus to spread through direct cell-to-cell contact.
Despite more than 30 years of research, many key aspects of the spread of HIV, the agent responsible for acquired immune deficiency syndrome (AIDS), have yet to be understood. One of those unresolved issues concerns the interactions between the virus and the environment in the human body. Traditionally, it has been badumed that infected cells release viral particles that diffuse and possibly infect other cells. But it is also possible that viral particles are directly transferred from one infected cell to the next by close contact. Until now, it was not known which of these modes of transmission prevailed in the tissues. "Studies on HIV replication in the lab are mostly conducted in simple cell culture experiments in plastic boxes that do not reflect complex architecture and tissue heterogeneity," says Dr. Oliver Fackler, Director of the Study, Center for Research on Integrative Infectious Diseases (ICID). ) at Heidelberg University Hospital.
In their approach, the Heidelberg researchers took into account that CD4-like T cells, the preferred cell type infected with HIV, are highly mobile in their physiological environment. They used a new cell culture system in which a three-dimensional scaffold was generated using collagen. This made it possible to maintain cell mobility and to monitor HIV-1 infected primary CD4 T cells in a tissue-like environment for several weeks. Using this innovative approach, researchers measured several factors that characterize cell motility, virus replication, and progressive loss of CD4 T cells. "This gave a very complex data set that was impossible to interpret without the help of scientists from other disciplines," says Dr. Andrea Imle, who worked on the project during his Ph.D. at ICID.
In the data badysis, the scientists who conducted the experiments collaborated with colleagues in the fields of image processing, theoretical biophysics and mathematical modeling. Together, they were able to characterize the complex behavior of cells and viruses and simulate it on a computer. This has made important predictions about the key processes that determine the spread of HIV-1 in these 3D cultures, confirmed by subsequent experiments.
Our interdisciplinary study is a good example of how iterative cycles of experimentation and simulation can help quantitatively badyze a complex biological process. "
Dr. Ulrich Schwarz, Institute of Theoretical Physics, University of Heidelberg
The data badysis revealed that the 3D environment of the cell culture system removes cell-free virus infection, while promoting the direct transmission of virus from one cell to the other. 39; another. "Our models have allowed us to integrate short films of single-cell microscopy with long-term measurements of the cell population and thus estimate the minimum time required for cell-to-cell contacts to transmit the infection." "says Dr. Frederik Graw of the BioQuant Center at Heidelberg University. The researchers hope that these results will eventually lead to new therapeutic approaches in the treatment of HIV.
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