What is it about?
Virus genomes have codon usage bias, which can be constrained by the host translational machinery. The effects of codon composition of a given mRNA on its own translation have been extensively reported in literature and is considered an important determinant of gene expression. However, how the codon usage of a viral genome affects the translation of host genes has been less explored. In fact, the virus replication requires a lot tRNA resource for the most demanded codons. Thus, the consumption of specific tRNAs for the virus replication could be an alternative manner, to control host protein synthesis and also to generate deleterious collateral effects. By integrating genomic, transcriptomic and proteomic data, we address whether the SARS-CoV-2 infection downregulates the most expressed genes in the host cell. Our analysis confirms this hypothesis. Extending this result to lung tissue we extract a list of 27 genes that could be affected by this mechanism of epistasis. We believe that our original hypothesis and analysis could be helpful for the challenging task of understanding the collateral effects of the COVID19.
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Why is it important?
Our finding provides a theoretical framework to understand the origin of some pathologies associated with COVID-19. It can be the starting point for new therapies. It also provides a new point of view in the virus-host interaction.
Perspectives
Our analysis shows a translation decrease in A2M, a plasmatic protein highly expressed in lung and artery that inhibits a broad spectrum of proteases, including trypsin, thrombin, and collagenase. Furthermore, A2M has a key role in regulating inflammatory processes because is able to bind to proinflammatory ligands. This is particularly relevant in the context of the COVID-19-derived cytokine storm. This finding indicates that the use of blood plasma from sans people, where this molecule is present, can help in the treatment of hyperinflammation and coagulopathies associated with COVID-19. As virus regulates the translation of the host by its codon usage, the biotechnological manipulation of the frequency of codons could be used to design attenuated viruses. We believe that our results shed light on how codon use could affect virus attenuation and would help decrease the damaging side effect, providing an exciting opportunity for live-attenuated vaccine development.
Luis Diambra
Centro Regional de Estudios Genomicos
Read the Original
This page is a summary of: SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage, Frontiers in Cell and Developmental Biology, August 2020, Frontiers,
DOI: 10.3389/fcell.2020.00831.
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