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California researchers say the world may be on the verge of human-to-human transmission of the H5N1 avian influenza virus with just one step of genetic engineering. Some experts say this deadly mutation could open the door to widespread human infection and even a pandemic.
In a study published Thursday in the journal Science, biologists at the Scripps Research Institute found that a single mutation in the hemagglutinin protein (the “H” in H5N1) has so far been linked primarily to sickening and killing birds and cattle. It was concluded that there is a possibility that the virus that has been used to kill humans can be transformed into the following pathogens. Targets human cells.
The findings come amid a state-mandated recall of raw dairy products due to an increasing number of H5N1 infections among dairy cows in California. Since the virus began infecting dairy cows in the country in March, infectious disease experts have said that unprotected contact between dairy workers and infected cows could allow the virus to evolve in a way that threatens humans. I’ve warned you.
Now, Scripps researchers suggest the path to such genetic changes may be much shorter than state and national health officials expected.
“This really surprised us,” said study co-author James Paulson, a biochemist and molecular biologist. This one mutation “meets the requirements for transmission,” he said.
Richard Webby, director of the World Health Organization’s Collaborating Center for Research on Animal and Avian Influenza Ecology, said the study’s findings go against common beliefs about the virus, specifically that it poses a threat to people. stated that multiple mutations are required. human.
“This is probably going to cause some ripples,” said Webby, who is also a research fellow in the department of infectious diseases at St. Jude Children’s Research Hospital in Memphis, Tenn., but was not involved in the Scripps study.
“I think most of us thought we were probably going to need multiple changes,” Webby said.
Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and the University of Tokyo, called the Scripps research team’s discovery an “important discovery” and said, “If you take into account the mutation rate of the influenza virus, it’s one in 10,000 particles. Therefore, this is important.” It is possible that the bovine H5N1 virus carries this mutation. ”
This “means the emergence of an H5N1 virus that can recognize human receptors is closer than we think,” he said.
A few months ago, Paulson and co-author Ian Wilson, a structural biologist at Scripps, decided to study the current H5N1 strain to see what it would take for it to cause a pandemic in humans.
Paulson is an expert in studying where and how different influenza viruses bind to cells when they invade a host. Wilson studies the structure of influenza virus proteins.
Researchers began their study by accessing global influenza databases and determining the genetic sequence of A/Texas/37/2024, the H5N1 avian influenza strain found in dairy farm workers in Texas. .
Next, they looked at the hemagglutinin protein, or spike, on the outer surface of the virus. This allows the virus to attach to the host cell membrane. Animals such as birds and humans have a variety of docking stations known as sialic acid receptors on their cells. The influenza virus needs the right spike, or key, to open the door to the cell and begin replicating.
More than 50 people have been infected with the H5N1 virus, and many of these cases involve dairy workers, who were likely sprayed into their eyes or noses with milk from infected cows. The researchers speculate that repeated exposures of this type allowed the virus to enter the cells, making it more forceful than a lockpick.
Normally, human-to-human transmission of influenza viruses is “primarily airborne through droplets from sneezes and coughs, and there are very few viruses,” Paulson said. “In this context, the virus needs to be able to recognize human-type receptors that bind to cells in the human respiratory tract in sufficient quantities to cause infection.”
To figure out what it takes for a virus to acquire the right docking facilities to trigger a human pandemic, Paulson, Wilson, and their team explore the boundaries between birds and humans, including the 1918 influenza outbreak. We investigated past influenza outbreaks that have surpassed the previous year. , 1957, 1968, 2009 — and some earlier studies.
They “selected a number of positions” on the hemagglutinin protein to mutate “one at a time” amino acids known to be involved in previous pandemics.
They then tried to conjugate these altered “H” proteins with human and avian receptor analogs.
Surprisingly, when glutamine at position 226 was replaced with leucine, glutamine no longer bound to bird receptors, but only to human receptors.
Paulson said this mutation is particularly interesting because it has occurred before in early strains of H5N1, including in around 2010. But “at the time, that single mutation wasn’t enough to change the specificity of the receptor. So what we didn’t expect was that the virus changed and evolved in subtle ways.” So a single mutation changed the specificity of the receptor.”
Researchers have demonstrated that a single genetic change can make a virus a threat to humans, but that doesn’t mean nature will follow that particular path. Many factors can influence the evolution of living things, and they cannot be easily predicted. Some say this may be why the virus has not yet acquired the ability to widely infect humans.
“Despite more than 50 human infections with bovine H5N1, we have yet to find evidence that this virus has adapted to humans on a larger scale,” Kawaoka said. “This suggests that additional mutations are likely needed for the virus to become fully transmissible between humans.”
Paulson acknowledged that “the whole biological context is very important.”
He said the study focused on just “one property that is important for the virus to be successful in adapting to a new host,” but said there are other properties that may be important as well. Ta.
For example, H5N1 was known in the past to cause severe respiratory illness. However, these days it is mostly associated with conjunctivitis and only rarely with mild upper respiratory disease.
“Why? I don’t think anyone knows,” Paulson said.
What is known is that this virus is rapidly moving between different species around the world, giving it ample opportunity to mutate and adapt.
As of Thursday, the Centers for Disease Control and Prevention had confirmed 58 H5N1 infections. Of these, 35 people were infected from handling infected dairy cows, 21 were infected from poultry, and the source of infection was unknown in two cases.
Additionally, 707 dairy herds in 15 states were also infected. And in the past 30 days alone, 23 commercial poultry farms in California have been infected with the virus, affecting more than 5.6 million birds.
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