New findings help explain how COVID-19 overpowers the immune system

Seeking to understand why COVID-19 is able to suppress the body's immune response, new research from the USC Leonard Davis School of Gerontology suggests that mitochondria are one of the first lines of defense against COVID-19 and identifies key differences in how SARS-CoV-2, the virus that causes COVID-19, interacts with mitochondrial genes when compared to other viruses.

These differences offer possible explanations as to why older adults and people with metabolic dysfunction have more severe responses to COVID-19 than other individuals, and they also provide a starting point for more targeted experiments that may help identify therapeutics, said senior author Pinchas Cohen, professor of gerontology, medicine and biological sciences and dean of the USC Leonard Davis School.

"If you already have mitochondrial and metabolic dysfunction, then you may, as a result, have a poor first line of defense against COVID-19. Future work should consider mitochondrial biology as a primary target for SARS-CoV-2 and other coronaviruses," he said.

The study, published January 8 in the Nature journal Scientific Reports, expands on recent findings that COVID-19 mutes the body's innate inflammatory response and reports that it seems to be doing so by telling mitochondrial genes what to do.

"We already knew that our immune response was not mounting a successful defense to COVID-19, but we didn't know why," said lead author Brendan Miller, a senior doctoral student in the Cohen Lab at the USC Leonard Davis School. "What we did differently was look at how the virus specifically targets mitochondria, a cellular organelle that is a crucial part of the body's innate immune system and energy production."

Making use of the vast amounts of public data being uploaded in the early days of the virus outbreak, the research team performed RNA sequencing analyses that compared mitochondrial-COVID interactions to those of other viruses: respiratory syncytial virus, seasonal influenza A virus, and human parainfluenza virus 3. These reanalyses identified three ways in which COVID-19, but not the other viruses, mutes the body's cellular protective response.

Chief among their findings is that SARS-CoV-2 uniquely reduces the levels of a group of mitochondrial proteins, known as Complex One, that are encoded by nuclear DNA. It is possible that this effect "quiets" the cell's metabolic output and reactive oxygen species generation, that when functioning correctly, produces an inflammatory response that can kill a virus, they say.

"COVID-19 is telling the cell not to make these Complex One-related proteins. That could be one way the virus continues to propagate," said Miller, who notes that this, along with the study's other observations, still needs to be validated in a targeted experiment.

The study also revealed that SARS-CoV-2 does not change the levels of the messenger protein, MAVS mRNA, that usually tells the cell an attack has happened. Normally, when this protein gets activated, it functions as an alarm system, warning the cell to self-destruct so that the virus cannot replicate, Miller said.

In addition, the researchers found that genes encoded by the mitochondria were not being turned on or off by SARS-CoV-2 - a process that is believed to produce energy that can help the cell evade a virus - at rates to be expected when confronted with a virus.

"This study adds to a growing body of research on mitochondrial-COVID interactions and presents tissue- and cell-specific effects that should be carefully considered in future experiments," said Cohen.

Brendan Miller, Ana Silverstein, Melanie Flores, Kevin Cao, Hiroshi Kumagai, Hemal H. Mehta, Kelvin Yen, Su- Jeong Kim, Pinchas Cohen.
Host mitochondrial transcriptome response to SARS-CoV-2 in multiple cell models and clinical samples.
Scientific Reports volume 11, 2021. doi: 10.1038/s41598-020-79552-z

Most Popular Now

Anticancer drug may improve outcome for severe COV…

Treating severe COVID-19 patients with the anticancer drug bevacizumab may reduce mortality and speed up recovery, according to a small clinical study in Italy and China ...

Pfizer and BioNTech commence global clinical trial…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced today that the first participants have been dosed in a global Phase 2/3 study to further evaluate the saf...

GSK and Vir Biotechnology expand coronavirus colla…

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) have signed a binding agreement to expand their existing collaboration to include the resear...

One dose of COVID-19 vaccine provokes strong immun…

Although clinical trial data are encouraging, real-world evidence with regard to the COVID-19 vaccine remains scarce. In particular, response to the vaccine among those p...

Johnson & Johnson announces submission of appl…

Johnson & Johnson (NYSE: JNJ) (the Company) announced that Janssen Biotech, Inc., has submitted an application to the U.S. Food and Drug Administration (FDA) requesting E...

Johnson & Johnson Announces Submission to Worl…

Johnson & Johnson (NYSE: JNJ) (the Company) announced that Janssen-Cilag International N.V. has submitted for Emergency Use Listing (EUL) to the World Health Organization...

Could a nasal spray prevent coronavirus transmissi…

A nasal antiviral created by researchers at Columbia University Vagelos College of Physicians and Surgeons blocked transmission of SARS-CoV-2 in ferrets, suggesting the n...

European Commission purchases additional 150 milli…

Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that the European Commission purchased an...

Neandertal gene variants both increase and decreas…

Last year, researchers at Karolinska Institutet in Sweden and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany showed that a major genetic risk ...

CureVac initiates rolling submission with European…

CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid (mRNA), today annou...

Pfizer and BioNTech publish data from in vitro stu…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced the publication in Nature Medicine of data from in vitro studies that demonstrate that sera from in...

Sanofi to provide manufacturing support to Johnson…

Sanofi has entered into an agreement with Janssen Pharmaceutical NV and Janssen Pharmaceuticals, Inc., two of the Janssen Pharmaceutical Companies of Johnson & Johnson, u...