The very first new variant of Sars-CoV-2, B.1.1.7 or then called Alpha, spread more effectively because it escaped the human immune system. However, unlike later Immunescape variants, mutations in the spike protein were not responsible for this, reports a team led by Lucy G. Thorne from University College London. Because the decisive changes are not directed against the antibodies, but against another component of the body’s defenses. As the working group now writes in “Nature”, the decisive changes concerned three genes that dampen the main alarm signals of the innate immune response.
The working group investigated which RNA and proteins are produced in cells of the respiratory tract when they are infected with alpha and the original version of the virus. She found that Alpha reads the three genes N, Orf9b and Orf6 much more strongly and produces more of the corresponding RNA and proteins. The resulting proteins disrupt several signaling pathways that an infected cell uses to detect the virus and alert the innate immune system. “This is how Alpha can multiply unnoticed in the early stages of the infection. We believe this will significantly improve his chances if it lands in someone else’s nose or lungs, ”Thorne said, according to a press release.
The protein encoded by Orf9b disrupts the transmission of signals from a receptor that registers the virus RNA that has penetrated, while the N protein and the product formed by Orf6 disrupt signaling pathways through which the alarm substance interferon is formed. Interferon, in turn, puts cells of the innate immune response and other body cells on alert, making it difficult for viruses to multiply. The study by Thorne’s team showed that the interferon concentrations measured in the cell culture were far lower than in all previous versions of the virus. The team suspects that the virus will multiply faster if there is a real infection.