Abstract
Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches.
Highlights
The recent SARS-CoV-2 pandemic has exerted an unprecedented pressure on the scientific community in the quest for novel antiviral approaches
The immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by extracellular matrix (ECM) remodeling in Ly6E∆hematopoietic stem cells (HSCs) mice
In this work we present a time-resolved study of the immune response of mice to a coronavirus, the murine hepatitis virus (MHV), in order to analyze the implications of gene Ly6E
Summary
The recent SARS-CoV-2 pandemic has exerted an unprecedented pressure on the scientific community in the quest for novel antiviral approaches. Given the similarities found amongst the members of the coronaviridae family [2,3], analyzing the global immune response to coronaviruses may shed some light on the natural control of viral infection, and inspire prospective treatments. This may well be achieved from the perspective of systems biology, in which the interactions between the biological entities involved in a certain process are represented. Genes 2020, 11, 831 by means of a mathematical system [4] Within this framework, gene networks (GN) have become an important tool in the modeling and analysis of biological processes from gene expression data [5]
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