If you’ve made it this far without getting covid, you may be thanking your genes.
A study published Wednesday in the journal Nature found that people who have a specific genetic variation of a protein in their body are more likely to never develop symptoms of covid, even if they are infected with the virus.
The protein in question is called human leukocyte antigen, or HLA. It is found on the surface of cells and helps alert the body’s immune system if something goes wrong, for example, your cell becomes infected with the coronavirus.
But the proteins are not identical to those of siblings, family members or friends, thanks to small differences at the genetic level that make each person’s HLA proteins unique.
“These are highly variable immune system molecules that sit on the surface of every cell in the body and are very different in each person,” said Jill Hollenbach, a professor of neurology at the University of California, San Francisco, who led the new investigation. .
In fact, HLAs are the most variable part of the human genome, which is by design.
“Genetic diversity is very important for the immune response,” said Neville Sanjana, an associate professor of biology at New York University and a faculty member at the New York Genome Center, who was not involved in the study. “When there are various pathogens that we are exposed to, not all people’s immune systems are going to respond to the pathogens in the same way.”
In the new study, Hollenbach and her team turned to a national database of bone marrow donors. People in the database had already had their HLA genetically sequenced. The researchers used this existing data to understand each person’s HLA proteins. Participants also reported if they had tested positive for covid from February 2020 to April 2021 and if they developed symptoms. All were unvaccinated.
The researchers noted that the study only included people who identify as white, because they did not have enough data on other races and ethnicities. However, they said the gene variant identified in the study appears to be associated with a lower chance of not developing symptoms in black people, although its effect is unclear in Asian, Hispanic, and American Indian/Alaska Native populations.
The study included nearly 1,500 people, all of whom were unvaccinated. Of these, 136 tested positive but never had symptoms, not even a bit of a runny nose or throat tickle.
The genetic code that tells cells how to build HLA proteins can have many small mutations that lead to different variants of the protein. Each person is born with two copies of the HLA gene, one from each parent.
The study found that 20% of people who never developed Covid symptoms had at least one copy of a variant called HLA-B*15:01, compared to just 9% of those with symptoms. People who carried two copies of this variant were more than eight times more likely than those who did not carry them to test positive for covid but remain asymptomatic.
But the HLA proteins are only one piece of the puzzle, the researchers found.
People with the HLA-B*15:01 variation also had T cells that could better detect the virus that causes covid, because they remembered previous coronavirus infections. (SARS-CoV-2, which causes covid, is not the only coronavirus that infects humans; several coronaviruses can cause common colds.) The viruses were similar enough to allow T cells to act quickly once SARS-CoV-2 infected the body.
In general, to clear viruses from a person’s cells, T cells work in conjunction with HLA proteins.
When a virus infects a cell, the HLA protein will take a piece of the virus and keep it on the cell’s surface. This acts as a kind of signal that signals the T cells that they can recognize the threat. When one that does appears, it attacks and kills the infected cell.
For people with the HLA-B*15:01 variant, this process seemed more effective than usual, allowing T cells to work more quickly to kill virus-infected cells before symptoms have time to develop. develop.
Hollenbach said the findings could help researchers develop better Covid drugs and vaccines.
Experts point out that the discovery is just one of many factors that determine whether a person will get sick from Covid.
“It’s a complex symptom at play here, it’s not the one, one-size-fits-all,” said Genevieve Wojcik, an assistant professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health who specializes in genetics. “Genetics is often only one part of the puzzle, and just one variant is an even smaller part of the puzzle.”
He noted that the study had limitations: Because the data was also collected only from white people, it leaves big gaps in our understanding of how genes play a role in communities of color that were hardest hit by Covid.
“HLA is one of the most diverse parts of the human genome,” Wojcik said. “We really need more diversity on a global scale if we want it to apply to all groups.”
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