Latest COVID-19 News: University Of Alabama And Polish Researchers Say SARS COV-2 Could Be Depleting Human Host Micro RNAs

Latest COVID-19 News: A team researchers from the University of Alabama at Birmingham-U.S., Jagiellonian University Medical College-Poland and  Nencki Institute of Experimental Biology-Poland postulate that one of the reasons of the anomalous traits of the SARS-CoV-2 versus existing human coronaviruses in terms of the severity of the disease it causes and also the long term health complications it causes in recovered COVID-19 patients could be due to the fact that the SARS-CoV-2 coronavirus acts as a microRNA "sponge." This action modulates host microRNA levels in ways that aid viral replication and stymies the host immune response and also causes a range of problems for the human host.
 
This new testable hypothesis results from analysis of current literature and a bioinformatic study of the SARS-CoV-2 coronavirus and six other coronaviruses.
 
The research findings are published in the American Journal of Physiology-Lung Cellular and Molecular Physiology. https://journals.physiology.org/doi/abs/10.1152/ajplung.00252.2020
 
Basically, human microRNAs, or miRNAs, are short, non-coding RNAs with 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, like infection by a virus.
 
These microRNAs or 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.
 
Hence the study team says 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.
 
This hypothesis is not new. Viral RNA sponges have been shown capable of removing host miRNA by the Epstein-Barr virus, and sponge activity has also been shown for the herpes and hepatitis C viruses.
 
Prior to the COVID-19 virus, there were two other coronaviruses that foreshadowed the devastating consequences of the COVID-19 virus. The first was the severe acute respiratory coronavirus, or SARS virus, in 2002; the second was the Middle East respiratory syndrome coronavirus, or MERS virus, in 2012. Neither had the high infectivity of the COVID-19 virus; but both were dangerous, causing 774 and 866 deaths, respectively, according to the National Institutes of Health.
 
The study team 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 ie the SARS, MERS and COVID-19 viruses and four non-pathogenic coronaviruses.
 
The team discovered that the number of target sites was elevated in the pathogenic viruses compared to the non-pathogenic strains.
 
In addition, 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.
 
By simply focusing on the 28 unique miRNAs for the COVID-19 virus, the study team 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.
 
Signiciantly, 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.
 
This also raises the question as to whether SARS-CoV-2 infections can subsequently give rise to cancer. https://www.thailandmedical.news/news/must-read-covid-19-questions-can-the-sars-cov-2-coronavirus-ultimately-also-cause-cancer
 
Corresponding author, Professor Dr James F. Collawn from the department of Cell Developmental Studies, University of Alabama at Birmingham told Thailand Medical New, "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 gave a detailed explanation of how the virus replicates inside an infected cell, including how the cell assists protein folding and how the virus begins assembly in the cell's endoplasmic reticulum and Golgi system. They also described many of the cellular proteins involved in these steps. This viral replication is known to produce stress and can provoke an unfolded protein response that causes a cell to undergo programmed death.
 
Dr Collawn further added, "Taken together, the viral strategies to increase the endoplasmic reticulum membranes and endoplasmic reticulum folding capacity and block unfolded protein response-associated translational attenuation, inflammatory responses and apoptosis are critical components for virus production."
 
The study team then showed, by citing literature, that nine of the specific cellular miRNAs that potentially are sponged by the COVID-19 virus could help achieve those viral needs.
 
Dr Collawn said, "The host miRNAs potentially controlled by the pathogenic human coronaviruses may be the key to gaining control over a very limited and specific set of miRNAs targets.”
 
The study team used computer-assisted gene ontology programs to find the genes and cellular pathways affected by the pathogenic human coronaviruses, and by the COVID-19 virus in particular.
 
Interestingly, the pathways the study team found "further supports the hypothesis that pathogenic human coronaviruses including the COVID-19 virus utilize the host miRNAs to adjust cellular processes in order to facilitate their viral protein production."
 
Dr Collawn added,Our hypothesis will require validations, starting with the assessment of these miRNA levels in infected tissues and ending with restoring the host miRNA balance with miRNA analogs. Furthermore, completely understanding how viruses take advantage of the endoplasmic reticulum and unfolded protein response pathway may also lead to the novel therapeutic strategies."
 
These new research findings may explain some other biological oddities of the COVID-19 virus.
 
Example of one such oddity is the varying susceptibilities to infection seen among patients, including a more severe morbidity and mortality for older patients. There may be individual differences among patient miRNA profiles, they said, and one "recent study has suggested that COVID-19 virulence in aged patients may be due to a lower abundance of miRNAs, and this may be a contributing factor in disease severity."
 
Yet another biological oddity that could be addressed by this new finding is the biological question as to how the virus co-exists in its normal animal source ie bats. The researchers said, "a recent study proposed that bats, considered as host of origin for the COVID-19 virus, have tolerance to potentially deadly viruses because of specific miRNAs."
 
A key concern however remains is that as these miRNAs depletion is also concerned with cancer development and progression; attention should also be focused and studied on this area as well.
 
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