Last Christmas, while the Omicron variant was bouncing across the United States, Mary Carrington inadvertently found herself at a superspreader event – an indoor party, packed with over 20 people, at least one of whom ended up transmitting the virus to most of the crowd. Guests.
After two years of avoiding coronavirus, Carrington felt sure her time had come: She was cuddling her niece, who tested positive shortly after, “and she was kissing me,” Carrington told me. But she didn’t catch the bug. And I just thought, Wow, I might be really resistant here.you weren’t thinking immunityAnd the I got thanks to multiple doses of the COVID vaccine. Instead, perhaps via some innate genetic quirk, their cells found a way to naturally fend off pathogen attacks instead.
Carrington, of all people, understood what that might mean. An expert in immunogenetics at the National Cancer Institute, she was one of the many scientists who helped discover A mutation that makes it impossible for most strains of HIV to enter human cells, making some people essentially immune to the effects of pathogens. Perhaps something similar could protect some rare individuals from SARS-CoV-2 as well.
The idea of resisting coronavirus is tricky enough that scientists around the world are doing it right now They scour people’s genomes for any hint of their existence. If that happens, they can use that knowledge to understand who the virus is most affected, or take advantage of it to develop better drugs to tame COVID. For individuals who have After to catch the infection–Rapidly declining population“Resistance is hanging down ‘like a superpower’ that people can’t help but think it should have,” says Paula Cannon, a geneticist and virologist at the University of Southern California.
As with any superpower, though, true resistance to SARS-CoV-2 infection is likely to be “very rare,” says Helen Su, an immunologist at the National Institutes of Allergy and Infectious Diseases. Carrington’s original intuition, for example, eventually proved wrong: She had recently returned from a trip to Switzerland and finally found herself entangled with the virus. Like most people who remained unharmed until recently, Carrington did so for two and a half years through a possible combination of vaccination, cautious behavior, social and economic privilege, and luck. It is entirely possible that resistance to the fungal coronavirus will not exist – or it may come with huge costs that are not worth the protection it offers in theory.
subordinate 1400 or so Viruses, bacteria, parasites, and fungi known to cause disease in humans, Jean-Laurent Casanova, a geneticist and immunologist at Rockefeller University, is sure of only three that can be eliminated by bodies with one-time genetic modifications: HIV, norovirus and the malaria parasite.
Perhaps the most well-known is the mutation that blocks HIV. About three decades ago, researchers, including Carrington, began looking for a small number of people who “we felt almost certain were exposed to the virus multiple times, almost certainly should have been infected,” yet that didn’t happen, she said. . I. Their superpower was simple: hmm Lacking functional copies of a gene called CCR5, which builds a cell surface protein that HIV needs in order to make its way to T cells, the virus’s preferred human prey. Just 1 percent of the population is of European descent Harboring this mutation, called CCR5-32, in duplicate; In other populations, the trait is still rare. However, researchers have taken advantage of his discovery to cook a file A powerful class of antiretroviral drugsVirus purification from two people with help Δ Bone marrow transplants 32The closest drug to developing a functional HIV treatment.
The stories are similar to those of these two other nurses. Genetic errors in the gene are called FUT2which sticks sugars to the outside of gut cells, can make people Norovirus resistance; A genome modification that erases a protein called DAVI from the walls of red blood cells, stood up Plasmodium vivaxAnd the One of several parasites that cause malaria, by making their way inside. Duffy mutation, affecting a gene called DARC / ACKR1he is very common in parts of Sub-Saharan Africa owned by those areas Paid rates From P. vivax The path of infection is down.
In recent years, with the advancement of genetic technologies, researchers have begun to investigate A handful of other infection resistance mutations Against other pathogens, among which Hepatitis B virus And the rota. But links are difficult to definitively identify, thanks to the number of people these types of studies have to enroll in, and also because infections are difficult to identify and detect. Absolutely; The case for SARS-CoV-2 is likely to be the same. For months, Casanova and a global team of collaborators have been in contact with thousands of people from around the world who believe they have the coronavirus in their genes. The best candidates were exposed to the virus — for example, by someone showing symptoms in their home — and continued to test negative for both the pathogen and its immune responses. But respiratory transmission is often disturbed by pure chance. The coronavirus can infiltrate people silently, and it doesn’t always leave antibodies behind. (The team will also test for less fluctuating T-cell responses.) People without obvious symptoms may not test at all, or may not test properly. The immune system alone can protect people from infection, especially in the short time after vaccination or illness. With HIV, a virus that causes chronic infections, lacks a vaccine, and spreads via obvious routes in focused social networks, “it was easier to identify those individuals” who had the virus visited but did not leave lasting roots within them, says Ravindra Gupta, a scientist Viruses at Cambridge University. SARS-CoV-2 will not provide science with the same ease of study.
It may not be possible to make a complete analogue of the HIV, malaria, and norovirus stories. True resistance can emerge in only a number of ways, and it tends to be born from mutations that prevent the pathogen’s ability to make its way into the cell, or the Xerox itself once it is inside. CCR5, Duffy, and FUT2-dropped polysaccharides, for example, serve as microbial landing platforms; Mutations steal insects from those roosts. In the event of an equivalent mutation to counter SARS-CoV-2, It may be found logically In, for example, ACE2, the receptor the coronavirus needs to break into cells, or TMPRSS2, a scissors-like protein that, for at least some variants, speeds up the invasive process. Already, researchers have found that some genetic variations can do just that Constantly require the presence of ACE2 on the cellsor Inject unwanted versions of TMPRSS2– Hints that there could be modifications that increase the abstraction of particles. But “the ACE2 enzyme is very important” for regulating blood pressure and keeping lung tissue healthy, said Su, of NIAID, who is one of several scientists collaborating with Casanova to find SARS-CoV-2 resistance genes. The mutation that keeps the coronavirus at bay may “fade out along with other aspects of a person’s physiology.” That gene modification can make it completely rare, debilitating, or even, as Gupta said, “incompatible with life.” speople with CCR5–Cannon told me that the Δ32 mutation, which stops HIV, is “essentially completely normal,” which means that HIV has somewhat messed up “choice for CCR5.” By contrast, the coronavirus has discovered how to exploit something vital to its host. An ingenious gas move.
The superpowers of genetic resistance can have other forms of kryptonite. A few strains of HIV have discovered a way to get around CCR5, and glomerulus to another molecule called CXCR4; Against this version of the virus, even people with the Δ32 mutation are not safe. A similar situation arose with Plasmodium vivax, which “we see in some Duffy-negative individuals,” suggesting that the parasite found a back door, says Diane Wirth, a malaria researcher at the Harvard School of Public Health. Evolution is a powerful strategy—and with SARS-CoV-2 bringing out variants at such a sharp clip, “I wouldn’t necessarily expect resistance to be a checkmate movement,” Cannon told me. BA.1, for example, evoke the mutations that made him less dependent on me Tempres 2 from delta.
However, protection doesn’t have to be all or nothing to be an advantage. partial Genetic resistance, too, can reshape a person’s disease course. With HIV, researchers have identified changes in groups of so-called HLA genes that, through their effect on killer-like T cells, It can reduce the risk of people progressing to AIDS. And a whole host of mutations that affect red blood cell function The parasites that cause malaria can often be kept at bay — although many of these changes come with a “huge human cost,” Wirth tells me, burdening people with serious clotting disorders that can sometimes become fatal.
With COVID-19, too, researchers are beginning to recognize some trends. Casanova, in the Rockefeller, is one of the many scholars who led efforts Unveiling The Importance looks like an alarm impervious compound Call Antivirus in early control from infection. People who inject clumps of protein rapidly in the hours following infection often do well against the virus. But those whose responses to interferon are weak or slow are more likely to develop serious illness; The same is true for people whose bodies make maladaptive antibodies that attack interferon as it passes messages between cells. There are other factors that can increase or decrease the risk of acute illness as well: the ability of cells to sense the virus early on; the amount of coordination between the different branches of defense; The brakes the immune system puts on itself, so it doesn’t jeopardize host tissues. Casanova and colleagues are also looking for mutations that might alter people’s risk of catching long-term COVID-19 and other consequences of the coronavirus. None of these searches will be easy. They should be at least simpler than those for infection resistance, Casanova told me, because the results they measure—the serious and chronic forms of the disease—are more straightforward to detect.
If resistance does not work, it should not be a disappointment. People do not need a complete siege to triumph over microbes – just a good enough defense. And the protection we were born with isn’t all the leverage we’ve got. Unlike genes, immunity can be easily built, modified and strengthened over time, especially with the help of vaccines. She told me it was likely these DIY defenses that kept Carrington’s case of COVID to a “moderate course.” Immunological protection is also a much more foolproof bet than a bet on what we may or may not inherit at birth. It’s better to rely on our protection I know We can cook ourselves, now that the coronavirus is with us forever.