New study shows that common genetic variation among people is responsible for mediating SARS-CoV-2 asymptomatic infection.
Have you ever wondered why some people never became sick from COVID-19? A study published recently in the journal Nature shows that common genetic variation among people is responsible for mediating SARS-CoV-2 asymptomatic infection. The results indicate that individuals having this variant never feel sick once infected. This exciting discovery was a result of a U.S.-Australia collaborative work led by Danillo Augusto, Ph.D., assistant professor at the University of North Carolina at Charlotte; Jill Hollenbach, Ph.D., professor at the University of California San Francisco; and Stephanie Gras, professor at La Trobe University in Australia.
The Role of Human Leukocyte Antigens (HLA)
The study focuses on a group of genes called human leukocyte antigens (HLA). These HLA genes code for proteins used by the immune system to identify your healthy cells and distinguish them from those infected by bacteria and viruses. The HLA system is critical for immune response and also highly variable among individuals. Because of the role of HLAs in fighting infection, the researchers wondered if there were specific variants that would make us more protected or susceptible to SARS-CoV-2 virus.
Danillo Augusto, assistant professor of Biological Sciences at UNC Charlotte. Credit: UNC Charlotte
Research Findings and Methodology
Hollenbach led the data collection, which started at the beginning of the pandemic. First, 29,947 unvaccinated individuals were screened using a mobile app designed specifically to track COVID-19 symptoms, and 1,428 reported a positive test for the virus. All individuals had their DNA previously sequenced to analyze their HLA genes. The researchers found that individuals having the genetic variant HLA-B*15:01 were much more likely to remain asymptomatic after infection. Impressively, this variant is present in about 10% of the population. In summary, individuals who had HLA-B*1501 in their genome could not dodge the infection, however, they escaped being sick.
Insights on Immune Response
"We hypothesized that their immune system could react so fast and powerfully that the virus was eliminated before causing any symptoms. It's like having an army that already knows what to look for and can tell by the uniform that these are the bad guys," according to Hollenbach.
HLA molecules display pieces of the virus to immune effector cells for inspection. The study used cells from individuals with HLA-B*15:01 who donated blood several years before the pandemic. The results showed that those individuals had memory T cells against a specific particle of SARS-CoV-2. Individuals who never had any contact with SARS-CoV-2 had already had some kind of previous exposure to other viruses and developed immunological memory against a particle from SARS-CoV-2.
Their immunological memory would elicit a much faster response and explain why those individuals remained asymptomatic. Still, it remained intriguing how they could develop immunological memory against SARS-CoV-2 without ever being exposed to this virus.
Cross-Reactive Immunological Responses
"It is widely known that other types of coronaviruses have caused seasonal colds for decades. We hypothesized that these individuals were exposed to seasonal coronaviruses in the past, and somehow, individuals specifically carrying HLA-B*15:01 could quickly kill cells infected by SARS-CoV-2 due to cross-reactive immunological responses. So, even if the bad guys changed the uniform, the army would still be able to identify them by their boots or maybe a tattoo on their arms. That is how our immunological memory works to keep us healthy," said Augusto.
After carefully analyzing the genomic sequences of all coronaviruses, the study showed that this SARS-CoV-2 particle recognized by HLA-B*15:01 in unexposed individuals is very similar to viral particles from other previous coronaviruses. The research demonstrated that T cells from pre-pandemic individuals could identify viral particles from past coronaviruses and SARS-CoV-2 with the same efficiency by showing crystal structures and affinity assays. It means those individuals created immunological memory for the previous coronaviruses, but because of the high similarity of this viral particle, their memory T cells can also recognize and kill SARS-CoV-2 very fast.
Implications and Future Research
The results show a mechanism for how individuals can avoid being sick from SARS-CoV-2 and the research group plans to continue learning about the response against this virus, which will result in better understanding of COVID-19 therapeutics and vaccines.
For more on this research, see Unmasking the Secret of COVID-19 "Super Dodgers."
Reference: "A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection" by Danillo G. Augusto, Lawton D. Murdolo, Demetra S. M. Chatzileontiadou, Joseph J. Sabatino Jr, Tasneem Yusufali, Noah D. Peyser, Xochitl Butcher, Kerry Kizer, Karoline Guthrie, Victoria W. Murray, Vivian Pae, Sannidhi Sarvadhavabhatla, Fiona Beltran, Gurjot S. Gill, Kara L. Lynch, Cassandra Yun, Colin T. Maguire, Michael J. Peluso, Rebecca Hoh, Timothy J. Henrich, Steven G. Deeks, Michelle Davidson, Scott Lu, Sarah A. Goldberg, J. Daniel Kelly, Jeffrey N. Martin, Cynthia A. Vierra-Green, Stephen R. Spellman, David J. Langton, Michael J. Dewar-Oldis, Corey Smith, Peter J. Barnard, Sulggi Lee, Gregory M. Marcus, Jeffrey E. Olgin, Mark J. Pletcher, Martin Maiers, Stephanie Gras and Jill A. Hollenbach, 19 July 2023, Nature.
DOI: 10.1038/s41586-023-06331-x
News
Injectable nanodevices could provide effective treatment for drug-resistant glioblastoma
The brain cancer glioblastoma is one of the most aggressive and treatment-resistant cancers known to medicine, carrying a median survival of just 12-15 months, even with the best available care. Now, researchers at the [...]
New Treatment Cuts “Bad” Cholesterol in Half for a Full Year
A single infusion of an experimental CRISPR-Cas9 therapy was reported to safely lower LDL cholesterol by 52.5% and triglycerides by 47.8%, as measured 12 months after treatment. What if one infusion could keep cholesterol [...]
Too Much RNA Can Drain a Cell’s Energy, Scientists Discover
A virus may cripple a cell’s power supply simply by producing too much of a molecule the cell needs to survive. New research from the Texas A&M College of Veterinary Medicine and Biomedical Sciences [...]
West African scientists warn of weakening health systems and urge stronger outbreak detection
LOME, Togo (AP) — West African laboratory scientists called on governments Friday to strengthen capacity to detect disease outbreaks to avoid another major outbreak, saying health systems across the region are becoming weaker. Participants [...]
A Little-Known Protein Could Point to a New Way To Treat Alzheimer’s
A study suggests that increasing SORLA protein levels could help treat Alzheimer’s disease and other disorders involving tau protein. Increasing SORLA, a protein with a protective role in the brain, helped mice withstand damage [...]
Cancer’s Hidden Antioxidant Shield Helps It Escape the Immune System
Blocking an antioxidant protein that tumors use to suppress immune attacks improved cancer immunotherapy responses in mice. Cancer cells can release antioxidants that interfere with the immune cells trying to kill them. Researchers have [...]
Scientists Find a Berry Compound That Helps Muscle Cells Burn Fat
Pterostilbene, a compound found naturally in some foods, affects how skeletal muscles process fats by stabilizing a protein called PPARδ and increasing its signaling activity. Pterostilbene, a natural compound found in blueberries, grapes, and [...]
Two Hidden Forces Help Build the Human Brain Before Birth
Scientists have uncovered two surprising forces that help guide how the human brain forms before birth. Before birth, the human brain is shaped in large part by an unusual class of stem cells known [...]
Researchers Uncover a Hidden Trigger Behind Chronic Inflammation
The findings offer new insights that could help guide the development of future therapies. A protein called human resistin may help flip on one of the immune system’s most powerful inflammatory switches. Researchers at [...]
Scientists Have Uncovered Previously Hidden Microbial Activity on Human Skin
The most abundant microbes on your skin may not be the ones doing most of the work. Human skin supports vast communities of bacteria, fungi, and viruses that can influence its protective barrier, immune [...]
Brazilian Tree Compounds Fight COVID-19 on Multiple Fronts
Scientists found compounds in a Brazilian tree that hit SARS-CoV-2 on multiple fronts, revealing a promising new lead in the search for COVID-19 treatments. Researchers have found that galloylquinic acids extracted from the leaves [...]
Cutting Two Amino Acids Slowed Prostate Cancer in Mice
A newly identified link between amino acid metabolism and cholesterol production may help prostate tumors adapt to hormone therapy. Prostate cancer can find ways around treatments designed to deprive tumors of the hormones they [...]
Largest-Ever Physics Survey Raises New Doubts About Our Model of the Universe
Physicists around the world remain deeply divided on key mysteries of the universe, from dark matter to quantum gravity. The standard cosmological model failed to gain majority support, and no leading theory dominated the [...]
Scientists Just Overturned a 100-Year-Old Belief About Bacteria in the Lungs
New findings raise questions about the role of microbes living in the lungs. More than 35 trillion bacteria live throughout the human body, forming microbiomes in the gut, mouth, lungs, skin, and urogenital tract. [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Novartis, Ionis drug failure spurs questions
Pelacarsen didn’t protect heart health despite lowering levels of a protein particle, “Lp(a),” in a large clinical trial — a result with important implications for cardiovascular drug research. Dive Brief: An RNA drug from [...]
