Do you think all viruses get milder with time?  This is not a killer bunny.

Do you think all viruses get milder with time? This is not a killer bunny.

As covid death modified The world has fallen to its lowest level since the pandemic’s early weeks in 2020, and it may be tempting to conclude that the coronavirus has become irreversibly milder. This idea fits with the common belief that all viruses start out badly and inevitably evolve to get nicer over time.

“There was a prevailing narrative that natural forces would solve this epidemic for us,” said Aris Katzurakis, an evolutionary biologist at the University of Oxford.

But there is no such natural law. The evolution of the virus often takes unexpected twists and turns. For many virologists, the best example of unpredictability is the pathogen that has ravaged rabbits in Australia for the past 72 years: the myxoma virus.

Myxoma has killed hundreds of millions of rabbits, said Andrew Reed, an evolutionary biologist at Penn State University, making it the deadliest vertebrate virus known to science. “It is certainly the greatest massacre of any vertebrate disease,” he said.

After its introduction in 1950, the myxoma virus became less lethal to rabbits, but Dr. Reed and colleagues discovered that it reversed course in the 1990s. And the last researchers studyreleased this month, found that the virus seemed to evolve to spread more quickly from rabbits to rabbits.

“There are still new tricks,” he said.

Scientists intentionally introduced the myxoma virus to Australia in hopes of eradicating the country’s invasive rabbit population. In 1859, a farmer named Thomas Austin imported twenty rabbits from England so he could hunt them on his farm in Victoria. Without natural predators or pathogens to stop them, they multiplied by the millions, eating enough plants to threaten local wildlife and sheep farms across the continent.

In the early twentieth century, researchers in Brazil presented a solution to Australia. They discovered myxoma virus in a type of cottontail rabbit native to South America. The virus, which is spread by mosquitoes and fleas, has caused little harm to animals. But when the scientists infected European rabbits in their lab, the myxoma virus was proven to be astonishingly lethal.

Rabbits developed skin nodules filled with viruses. The infection then spreads to other organs, usually killing the animals within days. This gruesome disease became known as myxomatosis.

Brazilian scientists have shipped samples of the myxoma virus to Australia, where scientists have spent years testing it in labs to make sure it only poses a threat to rabbits and not other species. A few scientists have injected myxoma viruses into themselves.

After the virus was proven safe, the researchers sprayed it into a few shellfish to see what would happen. The rabbits died quickly, but not before mosquitoes bit them and spread the virus to others. Soon, rabbits hundreds of miles away were also dying.

Soon after the myxoma was introduced, Australian virologist Dr. Frank Wiener began a careful and long-term study of her massacres. It was estimated that in the first six months alone, the virus killed 100 million rabbits. Dr. Viner determined in lab experiments that the myxoma virus killed 99.8 percent of the rabbits it infected, usually in less than two weeks.

However, myxoma virus has not eradicated Australian rabbits. During the 1950s, Dr. Wiener discovered why: the myxoma virus became less lethal. In his experiments, the most common strains of the virus killed at least 60 percent of rabbits. And rabbits killed by the strains took longer to succumb.

This development fits with the popular ideas of the time. Many biologists believe that viruses and other parasites inevitably evolve to be milder – and this is what happened a favour As the law of reduced virulence.

Zoologist Gordon Poole wrote in 1943: “Ancient parasites, by the process of evolution, have a much less detrimental effect on the host than recently acquired ones.”

According to the theory, the newly acquired parasites were deadly because they had not yet adapted to their hosts. The thinking went on keeping the host alive longer, and giving the parasites more time to reproduce and spread to new hosts.

The Virulence Reduction Act appears to explain why myxoma viruses have become less lethal in Australia – and why they are harmless in Brazil. Viruses have been evolving in South American cotton rabbits for much longer, to the point where they did not cause any disease at all.

But evolutionary biologists have begun to question the law’s logic in recent decades. Moderate growth may be the best strategy for some pathogens, but it is not the only one. “There are forces that can push the ferocity in the other direction,” said Dr. Katzurkis.

Dr. Reed decided to revisit the myxoma virus saga when he started his lab in Pennsylvania in 2008. “I knew it as a textbook case,” he said. “I started thinking, ‘Well, what’s going to happen next? “

No one has systematically studied myxoma virus after Dr. Wiener discontinued it in the 1960s. (He had good reason to abandon her, as he moved on to help eliminate smallpox.)

Dr. Reed arranged for Dr. Viner’s samples to be shipped to Pennsylvania, and he and his colleagues tracked more samples of fresh myxoma. The researchers sequenced the viruses’ DNA – something Dr. Viner couldn’t do – and conducted studies of infection in lab rabbits.

When they tested viral strains of the 1950s, they found they were less lethal than the initial virus, confirming Dr. Wiener’s findings. The mortality rate remained relatively low during the 1990s.

But then, things changed.

Newer viral strains killed more lab rabbits. And they often did it in a new way: by shutting down the animals’ immune systems. Rabbit gut bacteria, which are usually harmless, multiply and cause fatal infections.

“It was really scary when we first saw it,” Dr. Reed said.

Strangely enough, the wild rabbits of Australia did not suffer the horrific fate of Dr. Reed’s laboratory animals. He and his colleagues suspect that the new adaptation of viruses was a response to stronger defenses in rabbits. studies revealed that Australian rabbits have acquired new mutations in genes involved in the first line of defense against disease, known as innate immunity.

Because rabbits have developed stronger innate immunity, Dr. Reed and colleagues suspect that natural selection, in turn, favors viruses that can overcome this defense. This evolutionary arms race wiped out the advantage that hares had for a while. But these viruses have been shown to be worse against rabbits that have not developed this resistance, such as those in Dr. Reed’s lab.

The arms race is still unfolding. Nearly a decade ago, a new strain of myxoma virus appeared in southeastern Australia. This branch, nicknamed Lineage C, is developing much faster than other lineages.

Infection experiments indicate that the new mutations allow Lineage C to do a better job of transmitting from one host to another, according to the latest study by Dr. Reed and colleagues, which has not yet been published in a scientific journal. Many infected rabbits display a strange form of myxoma, which leads to massive swellings in their eyes and ears. It is precisely these places where mosquitoes like to drink blood – and where viruses have a better chance of reaching a new host.

Virologists see some important lessons that myxoma virus can provide as the world grapples with the Covid pandemic. Both diseases are affected not only by the genetic makeup of the virus, but by the defenses of its host.

As the pandemic continues its third year, people are more protected than ever thanks to immunity developed from vaccines and infections.

But the coronavirus, like myxomatosis, was not on an inevitable path to moderation.

The delta variant, which spiked in the US last fall, was more deadly than the original version of the virus. Delta was replaced by Omicron, causing less serious illness for the average person. But virologists at the University of Tokyo have done it experiments This suggests that the Omicron variant is evolving into more severe forms.

“We don’t know what the next step in evolution will be,” Dr. Katzorkis warned. “This chapter of the path of ferocity evolution has yet to be written.”

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