Uracil switch in SARS-CoV-2 genome alters innate immune responses

November 11, 2020

Tohoku University scientists have found that human editing enzymes are likely behind a type of mutation in the COVID-19 virus that stimulates the release of pro-inflammatory molecules called cytokines by immune cells in the body. The finding, published in the journal Scientific Reports, is important for understanding how the virus is evolving.

The genetic material of coronaviruses, including the SARS-CoV-2 virus that causes COVID-19 infection, is contained in a single strand of RNA. Coronaviruses have fewer genetic mutations compared to other RNA viruses because they have a kind of RNA-proofreading machinery that protects them. Nevertheless, they still do have some mutations, and scientists would like to understand how they come about and what their effects might be.

Tohoku University immunobiologist Emi Furusawa-Nishii and colleagues investigated the genome sequences of almost 8,000 SARS-CoV-2 viruses from an international database. They specifically looked for 'point mutations', in which a nucleotide base within the virus's RNA is switched to another base.

Their analyses found that virus strains that had evolved from the original one isolated in Wuhan, China had a disproportionate number of cytosine bases that were switched to uracil, in addition to a number of other nucleotide base switches. Further analyses of the nucleotide bases preceding and following these point mutations suggested they were caused by two types of human editing deaminase enzymes, called APOBECs and ADARs.

The scientists then wanted to study the effects of the mutations on macrophages: a type of white blood cell that forms part of the body's first line of defence, or its innate immunity. They tested the production of two pro-inflammatory cytokines, called tumour necrosis factor-alpha and interleukin-6, by human macrophage cell lines. The cells were stimulated with an RNA fragment from Wuhan-type or mutated-type SARS-CoV-2 viruses. Surprisingly, they found that the uracil-rich RNA fragment in the mutated-type SARS-CoV-2 viruses increased the production of the two cytokines.

"Our findings suggest that the point mutations we detected in SARS-CoV-2 viruses were caused by RNA editing as part of the human defence reaction against the infection," says Furusawa-Nishii. "They also show that the virus's evolution is increasing innate immune responses in the host."

The scientists say further studies are needed to determine whether this increased innate immune response helps efficient virus elimination or if it leads to an aggravation of symptoms.

Tohoku University

Related Immune Cells Articles from Brightsurf:

Gut immune cells may help send MS into remission
An international research team led by UCSF scientists has shown, for the first time, that gut immune cells travel to the brain during multiple sclerosis (MS) flare-ups in patients.

Immune cells sculpt circuits in the brain
Brain immune cells, called microglia, protect the brain from infection and inflammation.

How tumor cells evade the immune defense
Scientists are increasingly trying to use the body's own immune system to fight cancer.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Mapping immune cells in brain tumors
It is not always possible to completely remove malignant brain tumors by surgery so that further treatment is necessary.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Experience matters for immune cells
The discovery that immune T cells have a spectrum of responsiveness could shed light on how our immune system responds to infections and cancer, and what goes wrong in immune diseases.

Immune cells against Alzheimer's?
German researchers have developed a novel, experimental approach against Alzheimer's.

Read More: Immune Cells News and Immune Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.