Abstract
Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial–mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data (“nodes”) connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.
Highlights
In 1985, Helen Blau endowed the term “cellular plasticity” with its current meaning, that is, the ability of specific cells, under certain conditions, to turn into other cell lineages
What follows is a discussion on the different mechanisms of virus-induced plasticity, their meaning in the context of the propagation of the infectious program, and how Boolean networks can unravel the intrinsic complexity generated by the intersection of apparently different cellular programs
Whereas the potential of systems biology in general, and Boolean networks (BN) in particular, to unravel the complexity of virus-induced plasticity events is clear, the studies and data discussed here have illustrated some of the limitations of these approaches, which may underlie the fact that the field is still underdeveloped
Summary
In 1985, Helen Blau endowed the term “cellular plasticity” with its current meaning, that is, the ability of specific cells, under certain conditions, to turn into other cell lineages. Using cell fusion-based methods, she established the relationship between genotype and phenotype during cellular regeneration and tissue homeostasis [1] The gist of her paradigm-shifting discovery was that the differentiated state of a cell is subject to continuous regulation and revision, determining the identity of the cell within its surrounding tissue [2]. A classic categorization of plasticity includes three major forms: (1) Dedifferentiation, in which a differentiated cell reverts to a SC of the same lineage; (2) Trans-differentiation, in which a differentiated cell is converted into another lineage without passing through a pluripotent cell state; (3) Trans-determination, in which a cell changes its lineage from a SC or progenitor cell to a closely related cell type [12] Their numbers are low, SCs do exist in healthy adult tissues, indicating that they play physiological roles in homeostasis [13,14]. What follows is a discussion on the different mechanisms of virus-induced plasticity, their meaning in the context of the propagation of the infectious program, and how Boolean networks (a form of systems biology analysis) can unravel the intrinsic complexity generated by the intersection of apparently different cellular programs
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