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As covid death ratio With it falling to its lowest level worldwide since the first weeks of the pandemic in 2020, it may be tempting to conclude that the coronavirus has become irreversibly milder. This idea fits with the widespread belief that all viruses start badly and inevitably evolve to become milder over time.
“There is a dominant narrative that natural forces are going to unravel this epidemic for us,” said evolutionary biologist Aris Katzourakis of the University of Oxford.
But there is no such law of nature. The evolution of a virus often takes unexpected turns and turns. A prime example of this unpredictability for many virologists is a pathogen that has devastated rabbits in Australia for the past 72 years: myxoma virus.
Myxoma has killed hundreds of millions of rabbits, making it the deadliest vertebrate virus known to science, said Andrew Read, an evolutionary biologist at Pennsylvania State University. “Absolutely the greatest slaughter of any vertebrate disease,” he said.
After its introduction in 1950, myxoma virus became less virulent to rabbits, but Dr. Read and colleagues discovered that it had reversed course in the 1990s. And the researchers studyPublished this month, he found that the virus has evolved to spread even faster from rabbit to rabbit.
“It’s still getting new numbers,” he said.
Scientists deliberately introduced the myxoma virus to Australia in hopes of eradicating the invasive rabbit population in the country. In 1859, a farmer named Thomas Austin imported two dozen rabbits from England to hunt them on his farm in Victoria. Without natural predators or pathogens to stop them, they multiplied in the millions, eating enough vegetation to threaten native wildlife and sheep farms across the continent.
In the early 1900s, researchers in Brazil offered a solution to Australia. They discovered myxoma virus in a species of cottontail rabbit native to South America. Spread by mosquitoes and fleas, the virus did little harm to the animals. But when scientists infected European rabbits in their lab, the myxoma virus proved surprisingly lethal.
Rabbits developed skin nodules filled with viruses. Then the infection spread to other organs and usually killed the animals within a few days. This terrible disease has come to be known as myxomatosis.
Brazilian scientists sent samples of the myxoma virus to Australia; here scientists have tested for years in laboratories to make sure the virus only poses a threat to rabbits and not other species. A few scientists have even injected themselves with myxoma viruses.
After the virus was proven safe, the researchers sprayed the virus on several warrens to see what would happen. The rabbits died quickly, but not before the mosquitoes bit them and spread the virus to others. Soon, rabbits hundreds of kilometers away were dying, too.
Shortly after the introduction of myxoma, Australian virologist Dr. Frank Fenner embarked on a careful, long-term study of the massacre. He estimated that the virus killed 100 million rabbits in the first six months alone. Dr. In laboratory experiments, Fenner determined that myxoma virus killed 99.8 percent of infected rabbits, typically in less than two weeks.
Still, the myxoma virus did not wipe out the Australian rabbits. During the 1950s, Dr. Fenner discovered why: The myxoma virus has become less deadly. In their experiments, the most common strains of the virus killed up to 60 percent of the rabbits. And rabbits killed by the strains took longer to succumb.
This evolution fits with the popular ideas of the time. Many biologists believed that viruses and other parasites inevitably evolved to become softer – so what? known as the law of decreasing virulence.
The zoologist Gordon Ball wrote in 1943: “Parasites that have persisted through the course of evolution have far less detrimental effects on the host than those that have been acquired recently.”
The theory was that newly acquired parasites were deadly because they had not yet adapted to their host. Keeping a host alive longer gave the parasite more time to multiply and spread to new hosts.
The law of diminished virulence seemed to explain why myxoma viruses are becoming less deadly in Australia and harmless in Brazil. Viruses had been evolving in South American cottontail rabbits for much longer so that they did not cause any disease.
But evolutionary biologists have begun to question the logic of the law in recent years. Milder growth may be the best strategy for some pathogens, but it is not the only strategy. Dr. “There are forces that can push virulence in the other direction,” Katzourakis said.
Dr. When Read started his lab at Penn State in 2008, he decided to revisit the myxoma virus saga. “I knew this as a textbook case,” he said. “‘Well, what next?’ I’m starting to think.”
Dr. No one had systematically studied the myxoma virus after Fenner stopped in the 1960s. (She had good reason to dump him, as he continued to help. root out Smallpox.)
Dr. Read, Dr. He arranged for Fenner’s samples to be sent to Pennsylvania, and he and his colleagues also tracked down more recent samples of myxoma. The researchers sequenced the viruses’ DNA (something Dr. Fenner couldn’t) and conducted infection studies on laboratory rabbits.
When they tested the viral strains that were dominant in the 1950s, they discovered they were less virulent than the first virus, and Dr. They confirmed Fenner’s findings. And the death rate remained relatively low throughout the 1990s.
But then things changed.
Newer viral strains have killed most of the lab rabbits. And they often did it in a new way: by shutting down the animals’ immune systems. The gut bacteria of the normally harmless rabbits multiplied, causing deadly infections.
Dr. “When we first saw it, it was really scary,” Read said.
Strangely enough, wild rabbits in Australia, Dr. It did not suffer the gruesome fate of Read’s laboratory animals. He and colleagues suspect that the new adaptation in viruses is a response to stronger defenses in rabbits. Studies It revealed that Australian rabbits acquire new mutations in genes involved in the first line of disease defense, known as innate immunity.
As rabbits develop stronger innate immunity, Dr. Read and colleagues suspect that natural selection also favors viruses that can overcome this defense. This evolutionary arms race wiped out the short-lived advantage of wild rabbits. But these viruses, Dr. Like those in Read’s lab, it proved even worse against rabbits that had not developed this resistance.
And the arms race still continues. About a decade ago, a new strain of myxoma virus emerged in southeast Australia. This branch, called Lineage C, is growing much faster than other lineages.
Infection experiments, Dr. The new mutations allow Lineage C to do a better job of passing from host to host, according to Read and colleagues’ latest study, yet to be published in a scientific journal. Many infected rabbits exhibit a strange form of myxomatosis, which develops large bumps around their eyes and ears. It is precisely in these places that mosquitoes like to drink blood and viruses may have a better chance of reaching a new host.
Virologists see some important lessons the myxoma virus can offer as the world grapples with the Covid pandemic. Both diseases are affected not only by the genetic makeup of the virus, but also by the host’s defenses.
As the pandemic enters its third year, people are more protected than ever thanks to vaccines and immunity from infections.
But the coronavirus, like myxoma, is not on an inevitable path to moderation.
The Delta variant, which rose in the United States last fall, was more deadly than the original version of the virus. Delta has been replaced with Omicron, which causes less serious illness for the average person. But virologists at the University of Tokyo, experiments He suggests that the Omicron variant has evolved into more dangerous forms.
Dr. “We don’t know what the next step in evolution will be,” Katzourakis warned. “This chapter on the orbit of virulence evolution has yet to be written.”
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