COVID-19 Breakthrough: Scientists Discover How the SARS-CoV-2 Virus Evades Our Immune System

Suppression of NLRC5 in SARS-CoV-2-Infected Cells

The expression of the immune response gene ??NLRC5 (red purple) is suppressed in SARS-CoV-2 (green) infected cells. Credit: Koichi Kobayashi

A discovery by researchers at the Texas A&M College of Medicine could lead to new therapies to prevent the virus from proliferating in the human body.

The immune system is a complex network of cells and proteins that is designed to fight off infection and disease, especially those like the coronavirus, or SARS-CoV-2, that can cause numerous issues in the human body. But many individuals are still at risk of being infected with the coronavirus, letting it replicate in the body and further transmitting to other individuals.

The underlying mechanism of how SARS-CoV-2 escapes from the immune system has been poorly understood. However, researchers from the Texas A&M University College of Medicine and Hokkaido University have recently discovered a major mechanism that explains how SARS-CoV-2 can escape from the immune system and replicate in the human body. Their findings were recently published in the journal Nature Communications.

Novel Mechanism of SARS-CoV-2 Immune Escape

SARS-CoV-2 escapes from immune responses by cytotoxic T cells via impaired MHC-I expression which is caused by reducing both the amount and function of NLRC5. Credit: Koichi Kobayashi

“We found that the SARS-CoV-2 virus carries a suppressive gene that acts to inhibit a human gene in the immune system that is essential for destroying infected cells,” said Dr. Koichi Kobayashi, adjunct professor at the College of Medicine and lead author of the paper.

Naturally, the cells in a human’s immune system are able to control virus infection by destroying infected cells so that the virus cannot be replicated. The gene that is essential in executing this process, called NLRC5, regulates major histocompatibility complex (MHC) class I genes, which are genes that create a pathway that is vital in providing antiviral immunity. Kobayashi and his colleagues discovered this in 2012.

“During infection, the amount and activity of NLRC5 gene become augmented in order to boost our ability of eradication of viruses,” Kobayashi said. “We discovered that the reason why SARS-CoV-2 can replicate so easily is because the virus carries a suppressive gene, called ORF6, that acts to inhibit the function of NLRC5, thus inhibiting the MHC class I pathway as well.”

Koichi Kobayashi

Dr. Koichi Kobayashi, adjunct professor at the College of Medicine and lead author of the paper. Credit: Texas A&M College of Medicine

Kobayashi, who holds a joint appointment as a professor at Hokkaido University in Japan, collaborated with Paul de Figueiredo, associate professor in the Department of Microbial Pathogenesis and Immunology at the College of Medicine, on this paper.

Kobayashi and his team’s discovery shed light on the mechanism to how SARS-CoV-2 can replicate in the human body and can potentially lead to the development of new therapeutics to prevent the coronavirus from escaping the immune system and replicating in the body.

Although the introduction of COVID-19 vaccines, such as the Pfizer and Moderna vaccines, can lower an individual’s chance of contracting the virus, there is currently no permanent therapy that can entirely prevent a human from contracting SARS-CoV-2.

“We hope that this new discovery will allow us to develop a new drug that can block this gene so our immune system will be able to fight off the coronavirus for good,” de Figueiredo said.

Reference: “SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis” by Ji-Seung Yoo, Michihito Sasaki, Steven X. Cho, Yusuke Kasuga, Baohui Zhu, Ryota Ouda, Yasuko Orba, Paul de Figueiredo, Hirofumi Sawa and Koichi S. Kobayashi, 15 November 2021, Nature Communications.
DOI: 10.1038/s41467-021-26910-8

6 Comments on "COVID-19 Breakthrough: Scientists Discover How the SARS-CoV-2 Virus Evades Our Immune System"

  1. Howard Jeffrey Bender, Ph.D. | December 8, 2021 at 6:11 am | Reply

    All the coronaviruses and all their variants have different protein spikes, with Delta having one that’s more efficient at getting around the vaccines. Perhaps Omicron will, too. But the real problem is in the virus itself, not its protein shell, and why the most dangerous (MERS, SARS, and Covid-19) are so infectious. My independent research has found multiple one-in-a-million nucleotide sequence matches between all the coronaviruses and the human genome. Those sequences are the same as some of the loops of human tRNA. Using those loops and their amino acid code matches, viruses may be able to fool the nucleus membrane in cells to allow the virus to enter and associate with the human DNA, creating more opportunities for further infection. As this article says, Covid-19 has a suppressive gene that blocks our immune system, compromising it to no longer be able to stop the virus and other diseases from attacking organs throughout the body. Vaccines that attack the virus protein shells while ignoring their contents are doomed to failure from the Darwin effect, but recognizing these loops suggests a possible approach to successful coronavirus vaccines. Only the infection process is considered in my work, not the innate virulence of the virus. For more info, check out this YouTube, Coronavirus – Using Your DNA Against You.

  2. Thats because it has been engineered to do so. And then when it accidentally(?) escaped the lab, its caused all the problems it has. Thats what you do with gain of function research. You basically make a bioweapon thats hard to contain.

    • @Jason, love your post! It’s quite funny. You have a bright future ahead of you in comedy writing! Keep up the good work!

    • Would be interested to understand the probability of a “wild” virus incorporating ORF6 in a functional manner.

      Where else does ORF6 exist? is it somewhat rare? common?

      Its premature to jump to a conclusion it was engineered. But its perfectly reasonable for people to ask pertinent questions that could lead to that conclusion…

      Anyone mocking free inquiry has drunk the SJW kool aid and has no place in science

  3. Someone who lived a long time | December 8, 2021 at 2:39 pm | Reply

    Here is a simpler way to fight covid-19 then finding some hard to find horse medicine. Just walk into a drug store in America and say “Give me a shot of that Covid-19 Vaccine” Rinse and repeat three times and your done.

  4. So a week ago 2 Pfizer shots gave 87% protection. Now its’ 33%. WTF?

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