Prediction of SARS-CoV Interaction with Host Proteins during Lung Aging Reveals a Potential Role for TRIB3 in COVID-19
Open Access
- 1 January 2021
- journal article
- research article
- Published by Aging and Disease in Aging and disease
- Vol. 12 (1), 42-49
- https://doi.org/10.14336/ad.2020.1112
Abstract
COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 (TRIB3) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found TRIB3 expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of TRIB3 in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease.Keywords
This publication has 46 references indexed in Scilit:
- jvenn: an interactive Venn diagram viewerBMC Bioinformatics, 2014
- Cellular senescence: from physiology to pathologyNature Reviews Molecular Cell Biology, 2014
- Morpheus: a user-friendly modeling environment for multiscale and multicellular systems biologyBioinformatics, 2014
- The Hallmarks of AgingCell, 2013
- The Genotype-Tissue Expression (GTEx) projectNature Genetics, 2013
- Time-Response Evaluation by Transcriptomics of Methylmercury Effects on Neural Differentiation of Murine Embryonic Stem CellsToxicological Sciences, 2011
- A scaling normalization method for differential expression analysis of RNA-seq dataGenome Biology, 2010
- Surfactant protein C-deficient mice are susceptible to respiratory syncytial virus infectionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Mitogenic signalling and the p16INK4a–Rb pathway cooperate to enforce irreversible cellular senescenceNature, 2006
- Ink4a/Arf expression is a biomarker of agingJCI Insight, 2004