By utilizing innovative cell culture systems, quantitative image analysis, and computer simulations, researchers form the Heidelberg University Hospital show that tissue structure forces the HIV virus to spread through direct cell-to-cell contact.
The German-led research team challenged the generally accepted assumptions because they didn’t just utilize a two-dimensional cell culture for study of how HIV spreads. The findings were published in The Journal of Nature Communications.
Many aspects of how HIV, the causative agent of the acquired immune deficiency syndrome (AIDS), spreads haven’t been understood. A significant question concerned the interactions between the virus with the environment in the human body. Scientists traditionally assumed that infected cells release viral particles, which then diffuse and ultimately infect different cells. However, there is another consideration scientists pondered: could viral particles transfer directly from one infected cell to the adjacent one via neighboring contact? Surprisingly, for many laypersons, this process was not well understood and, in fact, it was unknown what the dominant mode of transmission for HIV was.
The German researchers considered that the so-called CD4 T helper cells, the preferred cell type infected by HIV, are highly motile in their physiological environment. They began by designing a novel cell culture system leveraging a three-dimensional scaffold, which was generated with the help of collagen. This way, they could maintain the cells’ mobility while monitoring primary CD4 T cells infected with HIV-1 in a tissue-like environment over the course of several weeks, reported Heidelberg University Hospital via EurekAlert!
Once the team had implemented this innovative approach, they were able to measure a number of factors that characterize cell motility, virus replication, and the gradual loss of CD4 T helper cells.
Dr. Andrea Imle noted, “This yielded a very complex set of data that was impossible to interpret without the help from scientists of other disciplines.” The data analysis required professionals from a range of fields, including image processing, theoretical biophysics and mathematical modeling. As a collaborative, the team was able to characterize the complex behavior of cells and viruses and simulate I on the computer—making it possible to make important predictions on the key processes that determine how HIV-1 spread in these 3D cultures. The cross-functional team replicated the experiments to confirm the findings.
Professor Ulrich Schwarz of the Institute for Theoretical Physics at Heidelberg University noted, “Our interdisciplinary study is a good example of how iterative cycles of experimentation and simulation can help to quantitatively analyze a complex biological process.
- German Research Foundation
- The Center for Modeling and Simulation in Biosciences (BIOM) of Heidelberg University
Oliver T. Frackler, University Hospital Heidelberg