Why is COVID-19 fatal when many other coronaviruses are innocent enough and cause colds?
A from the University of Alabama at Birmingham and Polish researchers propose an answer: the COVID-19 virus acts as a microARN “sponge”. This action modulates the host’s microARN grades to facilitate viral replication and counteract the host’s immune response.
This verifiable speculation is the result of research into existing literature and a bioinformatics examination of the COVID-19 virus and six other coronaviruses and is published in the American Journal of Physiology-Lung Cellular and Molecular Physiology.
Human microRNANs, or miRNANs, are short, non-coding RNA with about 22 bases that act on gene expression through their complementary pairing with mobile-specific messenger RNA, which silences messenger RNA, preventing it from translating into proteins. are a subtle controller of mobile metabolism or the mobile reaction to tension and unwanted challenges, such as infection with a virus.
MiRNAs account for only about 0. 01% of total RNA in mobiles and human tissues, while replication of viral RNA from a virus such as COVID-19 can succeed in 50% of overall mobile RNA. the COVID-19 virus has binding sites for express miARNs, and those sites are other link sites for miARNs discovered in the coronaviruses that cause the cold; the more pathogenic COVID-19 virus can selectively erase some miARNs to uncontroll the mobile and turn it into a harmful human coronavirus.
The sponge concept is not new. Viral RNA sponges have been shown to harbor miRNA with Epstein-Barr virus, and sponge activity has also been shown for herpes and hepatitis C viruses.
There were two human coronaviruses before the COVID-19 virus, officially called SARS-CoV-2, which foreshadowed the devastating consequences of the COVID-19 virus: the first severe acute respiratory coronavirus, or SARS virus, in 2002; the time of Middle East Respiratory Syndrome coronavirus, or MERS virus, in 2012. Nor did it have the greatest infectiousness of the COVID-19 virus; however, both were dangerous, causing 774 and 866 deaths respectively, according to the National Institutes of Health.
In this study, researchers used computer-aided bioinformatics research to search for target miARN sites for 896 mature human miARN sequences in seven other coronavirus genomes. These genomes included the 3 pathogenic coronaviruses (SARS, MERS and COVID-19) and 4 non-pathogenic coronaviruses. .
Researchers found that the number of target sites is higher in pathogenic viruses compared to non-pathogenic strains, and found that pathogeny human coronaviruses attracted sets of miARNs that differed from non-pathogenic human coronaviruses, in particular a set of 28 miARNs unique to the COVID-19 virus; SarS and MERS viruses had their own exclusive sets of 21 and 24 miARNs, respectively.
Focusing on the 28 miARNs unique to the COVID-19 virus, the researchers found that most of these miARNs are well expressed in bronchial epithelial mobiles and that their deregulation has been reported in human lung diseases that accompany lung cancer, chronic obstructive pulmonary disease. , cystic fibrosis and tuberculosis. In addition, it has been proposed that many miARNs act as tumor suppressants that target scheduled mobile death pathways, or apoptosis, which are intended to cause a mobile to kill itself when infected, mutated or by other means. The reduction of these miARNs has been linked to a poor diagnosis of cancer.
“Therefore, the COVID-19 virus, through its relief from the host miARN set, can announce the survival of the inflamed cells and, therefore, the continuation of their replication cycle,” the researchers said.
The authors gave a detailed explanation of how the virus replicates inside an inflamed cell phone, adding how the cell phone is helping with protein folding and how the virus begins to gather in the cell’s endoplasmic reticulum and Golgi system. . They also described many affected mobile proteins. This viral replication is known to produce stress and can cause a disseminated protein reaction that causes the programmed death of a mobile.
“Taken together,” the researchers said, “viral methods for building endoplastic reticle membranes and the ability to bend the endoplastic reticle and block translational attenuation, inflammatory reactions, and apoptosis related to the reaction of the disseminated protein are elements for virus production. “
The authors then showed, bringing the literature, that nine of the express cell miRNA potentially sponged through the COVID-19 virus can simply meet those viral needs.
Researchers used computer-aided genetic ontology systems to locate genes and cell paths affected by pathogenic human coronaviruses. COVID-19 virus in particular.
The pathways they discovered “encourage speculation that pathogenic human coronaviruses, adding the COVID-19 virus, use host miARN to fine-tune cellular processes to facilitate the production of viral proteins. “
“Our speculation will require validation,” they said, “starting with evaluating those degrees of miARN in inflamed tissues and ending with the recovery of the guest’s miARN balance with miARN analogues. In addition, completely how viruses take credit for the endoplastic reticle and spread. proteins. The reaction pathway can also lead to new healing strategies. “
This speculation through UAB researchers and Poles, all of whom contributed similarly to the article, would possibly cause other biological peculiarities of the COVID-19 virus.
One is the variable susceptibility to the infection observed in patients, adding more severe morbidity and mortality in older patients. There may be individual differences between miRN profiles of patients, they said, and a “recent study warned that COVID-19 virulence in elderly patients is possibly caused by a decrease in the abundance of miRN, possibly contributing to the severity of the disease. “
Another biological question is how the virus coexists in its general animal source: bats. “Normally,” the researchers said, “a recent examination proposed that bats, the host of the COVID-19 virus, have tolerance to potentially fatal viruses due to expressing miARN. “
University of Alabama at Birmingham
Bartoszewski, R. et coll. (2020) SARS-CoV-2 can generate cellular responses through host-specific miARN depletion. American Journal of Physiology – Cell and Molecular Lung Physiology. doi. org/10. 1152/ajplung. 00252. 2020.
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