As the spread of pathogens like the human immunodeficiency virus; is studying in a test tube, i.e. in two-dimensional cell cultures; even though it hardly reflects the much more complex conditions in the human body. Using innovative cell culture systems, quantitative image analysis, and computer simulations, an interdisciplinary team of scientists exploring HIV spreads in three-dimensional tissue-like environments.
Pathogens face varying microenvironments in vivo, but suitable experimental systems and analysis tools to dissect how three-dimensional tissue environments impact pathogens spread are lacking. The researchers’ results show that the tissue structure forces the virus to spread through direct cell-to-cell contact. Despite over 30 years of research, many key aspects of how HIV, the causative agent of the acquired immune deficiency syndrome (AIDS) spreads are still not understanding.
Exploring HIV spreads
Traditionally it has been assumed that infected cells release viral particles which then diffuse and eventually infect other cells. In addition, gravity rapidly converts standard suspension cultures of CD4 T cells into monolayers with dense cell packing. Within the concept of cell-associated HIV-1 transmission, culturing cells in such high density likely overrides the requirement for motility of donor and target cells to form cell–cell contacts for virus transmission.
One of these unresolved questions concerns the interactions between the virus with the environment in the human body. HIV replication in the lab are mostly conducting in simple cell culture experiments in plastic dishes; that do not reflect the complex architecture and heterogeneity of tissue. This allowed for maintaining the cells’ mobility and monitoring primary CD4 T cells infected with HIV-1 in a tissue-like environment over the course of several weeks.
Behaviour of cells and viruses
Together they were able to characterise the complex behaviour of cells and viruses and simulate it on the computer. This made it possible to make important predictions on the key processes that determine HIV-1 spread in these 3-D cultures; which were confirming by subsequent experimentation. Establish 3D collagen matrices as a synthetic; and tunable experimental system for analyzing HIV-1 spread; ex vivo in primary human CD4 T lymphocytes within a defined 3D environment.
However, the data analysis revealed that the 3-D environment of the cell culture system suppresses infection; with a cell-free virus while simultaneously promoting direct virus transmission from cell to cell; models allowing us to integrate short single-cell microscopy films; with long-term cell population measurements and thereby to estimate the minimal time span required for cell-to-cell contacts to transmit infection.