Is the COVID-19 Virus Pathogenic Because It Depletes Specific Host MicroRNAs?

Why is the COVID-19 virus deadly, while many other coronaviruses are fairly innocuous and just cause colds? A team of University of Alabama at Birmingham (UAB) and Polish researchers propose an answer--the COVID-19 virus acts as a microRNA "sponge." This action modulates host microRNA levels in ways that aid viral replication and stymy the host immune response. This testable hypothesis results from analysis of current literature and a bioinformatic study of the COVID-19 virus and six other coronaviruses. The hypothesis was published online on August 5, 2020, as a perspective in the American Journal of Physiology-Lung Cellular and Molecular Physiology. Human microRNAs (miRNAs) are short, non-coding RNAs made up of about 22 bases. They 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, such as infection by a virus. The miRNAs are only about 0.01 percent of total human cell and tissue RNA, while replicating viral RNA of a virus like the COVID-19 virus may reach 50 percent of the total cellular RNA. So, the UAB and Polish researchers say, 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 sponge idea is not novel.