The SARS-CoV-2 Alpha (B.1.1.7) variant mutated to evade our ‘innate immune system’, helping establish it as the world’s first ‘Variant of Concern’, finds a new study led by researchers at UCL and the Quantitative Biosciences Institute, University of California San Francisco.
Published in the journal Nature, the study shows the Alpha variant, first identified in the UK, evolved to make more of its ‘antagonism proteins’ that nullify the body’s first line of defense, known as the ‘innate immune system’.
The Alpha variant was first detected in November 2020 from a sample taken in September in the United Kingdom and began to spread quickly by mid-December. It was discovered that the variant, also known as lineage B.1.1.7, had one or more mutations on its spike protein.
CTV News Canada notes that the Alpha variant has since its discovery, evolved to include subsequent variants, like Delta and Omicron. By studying Alpha’s structure and function, scientists can better understand how virus variants evolve.
Scientists discovered the Alpha variant upped the production of specific proteins called ‘antagonism proteins’ that could help it suppress how infected cells signaled the immune system.
The evolution of enhanced antagonism protein expression
Every cell in the nose, throat, and lungs (airways) has a network of sensors that detect incoming viruses. These cells produce the protein interferon, which acts like a “burglar alarm,” eliciting a blanket anti-viral response, across both non-immune and immune cells (T cells and antibodies) to avert infection.
But it is the antagonism proteins that can help the virus to evade these sensors. And this is what the researchers wanted to study. It led to the discovery that antagonism proteins can help the virus to evade these sensors.
In the laboratory, researchers looked at lab-grown cells infected by this variant to monitor protein levels and look deeper into how the variant worked. They then compared the data to how cells responded to infection with the original strain of COVID-19 from Wuhan, China.
The study was the first to identify the evolution of enhanced antagonism protein expression in any virus and the first to implicate mutations in SARS-CoV-2 that increase infectiousness but do not involve the ‘spike’ protein.
Co-first author Dr. Lucy Thorne (UCL Division of Infection & Immunity) said: “We wanted to know what made the SARS-CoV-2 Alpha variant special. We found that that the SARS-CoV-2 Alpha variant had adapted to avoid triggering our defensive frontline innate immune response much better than the first wave viruses.”
“We discovered it does this by making more of the virus proteins that can disable the innate immune system. These proteins are called N, Orf6, and Orf9b, and are known as innate immune antagonists.”
“By mutating to evade our innate immune system, the Alpha variant can replicate under the radar in the early stages of infection, which we think significantly increases its chances of infecting a person when it lands in their nose, throat, or lungs. For a virus this is a resounding success, enabling it to more efficiently spread from person to person.”
Commenting on the findings, co-senior author Professor Greg Towers (UCL Division of Infection & Immunity), said: “We have never seen anything like this before; we know viruses adapt and we expect to see the proteins adapting so they work better in humans. But Alpha is using its antagonism proteins, that help evade detection a little bit, and cranking up how much it makes. That is unique.”
The importance of this research
Co-first author Dr. Ann-Kathrin Reuschl (UCL Division of Infection & Immunity) added: “It will be fascinating to see how the other variants, such as Delta and Omicron, perform comparatively in our lung epithelial systems. Whether the viruses rely on similar approaches to innate antagonism or have evolved distinct strategies to evade the immune defenses, will teach us not only about the viruses themselves but also about human biology.”
“The virus will keep evolving and adapting to the host, and every time it will adapt better and better,” Lorena Zuliani-Alvarez, a co-author and senior scientist at the QBI, said in the release. “That’s why Omicron has 53 mutations.”
Primarily, the research shows that the spike protein isn’t the only factor researchers should be thinking about when designing treatments to help those infected with COVID-19.
