The peptide NQK-Q8 (light color), part of the SARS-CoV-2 spike protein that the virus uses to enter cells, bound to the groove of HLA-B*15:01 (orange color). This figure shows the crystal structure of HLA-B*15:01 in complex with the spike-derived peptide NQKLIANQF from the SARS-CoV-2 virus, published by Augusto et al., 2023 (Nature) (PDB Entry – 8ELH) It is based on.Credit: Andre Luis Lourenço
New study shows common genetic variations among people are involved in mediating SARS-CoV-2 Asymptomatic infection.
Have you ever wondered why some people don’t get sick? COVID-19 (new coronavirus infection)? Research recently published in journals Nature We show that common genetic variations among people are responsible for vectoring asymptomatic transmission of SARS-CoV-2. The results show that people with this mutation do not feel sick once infected. This exciting discovery was the result of a joint U.S.-Australian study led by Dr. Danilo Augusto, an assistant professor at the University of North Carolina at Charlotte. Dr. Jill Hollenbach, Professor, University of California, San Francisco. Stephanie Gras, a professor at La Trobe University in Australia.
The role of human leukocyte antigens (HLA)
The research focuses on a group of genes called human leukocyte antigens (HLAs). These HLA genes code for proteins that the immune system uses to identify healthy cells and distinguish them from cells infected with bacteria or viruses. The HLA system is important for the immune response, but varies widely between individuals. Because of the role of HLA in fighting infections, researchers are wondering whether there may be certain variants that make us more protected against or more susceptible to SARS-CoV-2. I thought about it. virus.
Danilo Augusto, assistant professor of biological sciences at UNC Charlotte;
Research results and methodology
Hollenback led the data collection that began early in the pandemic. First, 29,947 unvaccinated people were screened using a mobile app specifically designed to track COVID-19 symptoms, and 1,428 people tested positive for the virus. reported.everyone has their own DNA It has been pre-sequenced for HLA gene analysis. Researchers found that people with the gene mutation HLA-B*15:01 were much more likely to remain asymptomatic after infection. Remarkably, this variant is present in approximately 10% of the population. In summary, those who had HLA-B*1501 in their genome could not avoid infection, but they were spared from getting sick.
Insights into the immune response
“We hypothesized that their immune systems would respond so quickly and strongly that the virus would be cleared before they could cause symptoms. It would be because they already know what to look for. It’s like having an army where you can tell by their uniforms that they’re bad guys,” Hollenback said.
HLA molecules present parts of the virus to immune effector cells for testing. The study used cells from individuals with HLA-B*15:01 who donated blood several years before the pandemic. The results showed that these people had memory T cells against specific particles of SARS-CoV-2. People who had never had any contact with SARS-CoV-2 had already been exposed to other viruses in some way and had developed an immune memory against particles from SARS-CoV-2.
Their immunological memory would elicit a much faster response and explain why those people remain asymptomatic. Still, it remained intriguing how they were able to develop immune memory against SARS-CoV-2 without ever being exposed to this virus.
cross-reactive immune response
“It is widely known that other types of coronaviruses have been causing seasonal colds for decades. We know that these people have been exposed to seasonal coronaviruses in the past and that somehow Alternatively, we hypothesized that people specifically carrying HLA-B*15:01 could rapidly kill cells infected with SARS-CoV-2 through a cross-reactive immune response. So even if the bad guys changed their uniforms, the military would be able to identify them by a tattoo on their boots or maybe an arm. That’s how our immunological memory works to keep us healthy. ” Augusto said.
After careful analysis of the genome sequences of all coronaviruses, this study found that this SARS-CoV-2 particle, recognized by HLA-B*15:01 in unexposed individuals, was It was shown to be very similar to particles. By presenting crystal structures and affinity assays, this study demonstrated that T cells from pre-pandemic individuals can discriminate between past coronaviruses and SARS-CoV-2 virus particles with equal efficiency. This means that these individuals have created immunological memory against previous coronaviruses, but because of the high similarity of this viral particle, memory T cells also recognize SARS-CoV-2 very quickly. can be killed.
Implications and future research
The results point to a mechanism for how individuals avoid illness caused by SARS-CoV-2, and the research group plans to continue learning about responses to the virus, which could lead to treatments for COVID-19. Your understanding of the law and vaccines will deepen.
For more information about this study, see “Uncovering the secrets of the COVID-19 ‘Super Dodgers’.” Reference: “Common alleles of” HLA Asymptomatic SARS-CoV-2 Infection is Associated with .
Danilo G. Augusto, Lawton D. Murdlo, Demetra SM Chatzileontiadu, Joseph J. Sabatino Jr., and Tasneem Yousufari , Noah D. Peiser, Xochitl Butcher, Kelly Kaiser, Caroline Guthrie, Victoria by W. Murray, Vivian Pe, Sannidhi Sarvadavabatla, Fiona Beltran, Gurjot S. Gill, Carla L. Lynch, Cassandra Yun, Colin T. Maguire, Michael J. Peluso, Rebecca Ho, Timothy J. Henrik, Stephen G. Deeks, Michelle Davidson, Scott Lu, Sarah A. Goldberg, J. Daniel Kelly, Jeffrey N. Martin, Cynthia A. Vieira-Green, Stephen R. Spellman, David J. Langton, Michael J. Dewar-Aldiss, Corey Smith, Peter J. Bernard, Seulgi Lee, Gregory M. Marcus, Jeffrey M. E. Holguin, Mark J. Pletcher, Martin Myers, Stephanie Gras, Jill A. Hollenback, July 19, 2023, Nature.
Source: scitechdaily.com
