SARS-CoV-2 Acts as Sponge to Delete Specific Host microRNAs, Making it More Dangerous than Other Coronaviruses

A team of researchers have proposed that the SARS-CoV-2 virus is more deadly than many other coronaviruses because the COVID-19 virus acts as a microRNA “sponge.” This action modulates host microRNA levels in ways that aid viral replication and stymies the host immune response.

Researchers from the University of Alabama at Birmingham (Birmingham, AL, USA) and Poland have proposed this testable hypothesis results based on their analysis of current literature and a bioinformatic study of the COVID-19 virus and six other coronaviruses.

Human microRNAs, or miRNAs, are short, non-coding RNAs with about 22 bases that act to regulate gene expression by their complementary pairing with specific messenger RNAs of the cell. That pairing silences the messenger RNA, preventing it from being translated into a protein. Thus, miRNAs are a fine-tuned controller of cell metabolism or the cell’s response to stress and adverse challenges, like infection by a virus. The miRNAs are only about 0.01% of total human cell and tissue RNA, while replicating viral RNA of a virus like the COVID-19 virus may reach 50% of the total cellular RNA. Hence, the UAB and Polish researchers believe that if the COVID-19 virus has binding sites for specific miRNAs - and these sites are different from the binding sites for miRNAs found on coronaviruses that cause colds - the more pathogenic COVID-19 virus may selectively sponge up certain miRNAs to dysregulate the cell in ways that make it a dangerous human coronavirus. The two human coronaviruses prior to the COVID-19 virus - the severe acute respiratory coronavirus, or SARS virus, and the Middle East respiratory syndrome coronavirus, or MERS virus, - were both dangerous, but did not have the high infectivity of the SARS-CoV-2 virus, which causes COVID-19.

For their study, the researchers used computer-aided bioinformatic analysis to find potential miRNA target sites for 896 mature human miRNA sequences on seven different coronavirus genomes. These genomes included the three pathogenic coronaviruses - the SARS, MERS and COVID-19 viruses - and four non-pathogenic coronaviruses. The researchers found that the number of target sites was elevated in the pathogenic viruses compared to the non-pathogenic strains. Furthermore, they found that pathogenic human coronaviruses attracted sets of miRNAs that differ from the non-pathogenic human coronaviruses. In particular, a set of 28 miRNAs were unique for the COVID-19 virus; the SARS and MERS viruses had their own unique sets of 21 and 24 miRNAs, respectively.

Focusing on the 28 unique miRNAs for the COVID-19 virus, the researchers found that the majority of these miRNAs are well expressed in bronchial epithelial cells, and their dysregulation has been reported in human lung pathologies that include lung cancers, chronic obstructive pulmonary disease, cystic fibrosis and tuberculosis. Furthermore, many of the miRNAs have been proposed to act as tumor suppressors that target the pathways for programmed cell death, or apoptosis, that are supposed to make a cell kill itself when infected, mutated or stressed in other ways. Reduction of those miRNAs has been associated with poor cancer prognosis.

“Hence, the COVID-19 virus - by its potential reduction of the host’s miRNA pool - may promote infected cell survival and thus continuity of its replication cycle,” the researchers said.

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University of Alabama at Birmingham