2023-08-10 10:28:39
Updated Thursday, August 10, 2023 – 10:28
Causes alterations in cellular mitochondria that are maintained beyond infection
A health worker carries out analysis of Covid samples. JAVIER BARBANCHO
Since almost the beginning of the covid-19 pandemic caused by the SARS-CoV-2 virus, the scientific community has tried to determine why this virus causes such negative long-term effects compared to those created by most other coronaviruses.
The investigation begins to give some answers. Among them, the one that appears published in Science Translational Medicine and what does it suggest new approaches to treat covid-19, according to the research team made up of a multi-center consortium led from the Children’s Hospital of Philadelphia, United States (CHOP) and the Covid-19 International Research Team (COV-IRT).
This scientific platform has discovered that mitochondria genesthe energy producers of our cells, can be negatively affected by the virus, leading to a dysfunction in multiple organs beyond the lungs.
Mitochondria are found in every cell in our body. The genes responsible for generating mitochondria are scattered both in the ADN nuclear located in the nucleus of our cells as in the mitochondrial DNA (mtDNA) located within each mitochondria.
Previous studies have shown that the SARS-CoV-2 proteins they can bind to mitochondrial proteins in host cells, potentially leading to mitochondrial dysfunction.
To understand how SARS-CoV-2 affects mitochondria, researchers from CHOP’s Center for Mitochondrial and Epigenomic Medicine (CMEM), together with their colleagues at COV-IRT, analyzed the mitochondrial gene expression to detect differences caused by the virus. To do this, they analyzed a combination of nasopharyngeal and autopsy tissues from affected patients and animal models.
Recovered in the lungs, not in other organs
Joseph Guarnieria CMEM postdoctoral researcher at CHOP, points out that samples of patient tissue allowed us to observe how mitochondrial gene expression was affected “by beginning and end of disease progressionwhereas animal models allowed us to fill in the blanks and observe the progression of differences in gene expression over time.”
The study found that, in autopsy tissue, the expression of the mitochondrial gene had recovered in the lungsbut mitochondrial function remained suppressed in the heart, as well as in the kidneys and liver.
By studying animal models and measuring the moment when the viral load peaked in the lungs, the mitochondrial gene expression in the cerebellum, although SARS-CoV-2 was not observed in the brain. Additional animal models revealed that during the middle phase of SARS-CoV-2 infection, mitochondrial function in the lungs began to recover.
Taken together, these results reveal that host cells respond to initial infection in a way that involves the lungs, but over time, mitochondrial function in the lungs is restoredwhile, in other organs, particularly the heart, mitochondrial function remains impaired.
For Douglas C. Wallacedirector of CMEM at CHOP, this study provides strong evidence that stop watching covid-19 like an erespiratory tract disease strictly superiors and begin to see him as a systemic disorder that affects multiple organs”.
Potential therapeutic target
“The ongoing dysfunction that we see in organs other than the lungs suggests that mitochondrial dysfunction could be causing long-term damage to internal organs of these patients”.
Although future studies using these data will explore how systemic immune and inflammatory responses may be responsible for more severe disease in some patients, the research team found a Potential therapeutic target in microRNA 2392 (miR-2392)which was shown to regulate mitochondrial function in the human tissue samples used in this study.
“This microRNA was upregulated in the blood of patients infected with SARS-CoV-2, which is not something we would normally expect to see,” says co-senior author Afshin Beheshtibiostatistician and visiting researcher in The Broad Institute, en Cambridgeand founder and president of COV-IRT.
In his opinion, “neutralizing this microRNA could prevent the replication of the virus, providing an additional therapeutic option for patients who run the risk of more serious complications disease-related.”
Earlier this year, the Fundacin Gates provided funding to Douglas C. Wallace and MEMC to investigate how mtDNA variation among global populations might affect mitochondrial function and thus the individual susceptibility to SARS-CoV-2.
According to Wallace, the demonstration that SARS-CoV-2 markedly affects the mitochondrial function “supports the hypothesis that individual differences in mitochondrial function might be a factor in the single gravity of covid-19″.
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