Cell cell contact responsible for the spread of the HIV virus

Washington: Scientists have explored how HIV spreads in three-dimensional tissue-like environments. The spread of pathogens such as the Human Immunodeficiency Virus (HIV) is often studied in a test tube, which is found in two-dimensional cell cultures, although it hardly reflects the much more complex conditions of the human body. Use of innovative cell culture systems, quantitative image badysis and computer simulations. The results of the research show that the structure of the tissue forces the virus to spread through direct cell-to-cell contact.

After 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.

"Studies on laboratory replication of HIV are mainly conducted in simple cell culture experiments in plastic boxes that do not reflect complex architecture and tissue heterogeneity," says Professor Oliver Fackler, director of study at the University Hospital Heidelberg. The results are published by The Journal Nature Communications.

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," says Professor Ulrich Schwarz of the University of Heidelberg.

In their approach, the 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 set of data that was impossible to interpret without the help of scientists from other disciplines," says Dr. Andrea Imle, who worked on the project during his doctorate.

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 allowed us to integrate short films of single-cell microscopy with long-term measurements of the cell population and thus estimate the minimum time interval required for cell-to-cell contacts to transmit. the infection, "says Dr. Frederik Graw, of the University of Heidelberg. The researchers hope that these results will eventually lead to new therapeutic approaches in the treatment of HIV.

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