With the Covid death rate falling to its lowest level in the world since the early weeks of the pandemic in 2020, it may be tempting to conclude that the irreversible coronary virus is milder. This notion coincides with the widespread belief that all viruses start to get worse over time, inevitably becoming softer.
“This has been the main story of how natural forces will solve this pandemic,” said Aris Katzourakis, an evolutionary biologist at Oxford University.
But there is no such thing as a natural law. The evolution of a virus often takes unexpected turns. For many virologists, the best example of this surprise is a pathogen that has been ravaging Australian rabbits for 72 years: the 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. “It’s absolutely the biggest massacre of vertebrate diseases,” he said.
Since its introduction in the 1950s, the myxoma virus has not been so deadly to rabbits, but Dr. Read and his colleagues found that it turned the tide in the 1990s. And the latest research from researchers, published this month, found that the virus was evolving to spread from rabbit to rabbit even faster.
“He’s still picking up new tricks,” he said.
Scientists deliberately introduced the myxoma virus into Australia with the aim of eradicating invasive rabbit populations from the country. In 1859, a farmer named Thomas Austin imported two dozen rabbits from England to hunt on his Victorian farm. Without natural prey or pathogens to sustain them, they multiplied by millions, eating enough vegetation to threaten the local fauna and sheep herds across the continent.
In the early 1900s, Brazilian researchers offered a solution to Australia. Mixoma virus was found in a species of rabbit with a native tail in South America. The virus spread by mosquitoes and fleas did little harm to the animals. But when scientists infected European rabbits in their laboratory, the myxoma virus was deadly.
Rabbits developed virus-infected skin nodules. The infection then spread to other organs, usually killing the animal within a few days. This terrible disease was known as myxomatosis.
Brazilian scientists sent samples of the myxoma virus to Australia, and scientists spent years testing it in laboratories to ensure that it was only a threat to rabbits and not other species. Some scientists also injected myxoma virus into them.
After proving the virus was safe, researchers rarely threw a warren at it to see what would happen. The rabbits died quickly, but not before the mosquitoes bit and spread the virus to others. Shortly afterwards, rabbits hundreds of miles away were also being killed.
Shortly after the introduction of myxoma, Australian virologist Dr. Frank Fenner began a rigorous and lengthy examination of his massacre. In the first six months alone, the virus was estimated to have killed 100 million rabbits. Dr. Fenner determined in laboratory experiments that 99.8 percent of rabbits were infected with myxoma virus, typically within two weeks.
However, the myxoma virus did not wipe out Australian rabbits. During the 1950s, Dr. Why Fenner found it: Myxoma virus was less deadly. In his experiments, the most common strains of the virus killed as many as 60 percent of rabbits. And the rabbits killed by the strains took longer to kill.
This evolution coincided with the popular ideas of the time. Many biologists believed that viruses and other parasites eventually evolved to become lighter – known as the law of declining virulence.
“Old parasites, according to the evolutionary process, have a much less harmful effect on the host than recently acquired ones,” wrote zoologist Gordon Ball in 1943.
According to the theory, the newly taken parasites were deadly because they had not yet adapted to their hosts. Keeping a host alive longer gave the parasites more time to reproduce and spread to new hosts.
The law of declining virulence explained why myxoma viruses became less deadly in Australia, and why they were harmless in Brazil. Many of the viruses were evolving in South American cotton-tailed rabbits, and did not cause disease.
But evolutionary biologists have come to question the logic of the law in recent decades. Slower growth may be the best strategy for some pathogens, but it is not the only one. “There are forces that can push virulence in another direction,” Drs. said Katzourakis.
Dr. Read decided to review the myxoma virus saga when it began its laboratory in Penn State in 2008. “I knew it as a case of textbooks,” he said. “I started thinking, ‘Well, what happens next?'”
No one was diagnosed with the myxoma virus after Dr. Fenner stopped in the 1960s. (He had good reason to cancel it because it helped eradicate the smallpox.)
Dr. Read Dr. To send samples of Fenner to Pennsylvania, and he and his colleagues also followed newer samples of myxoma. Researchers sequenced virus DNA – Dr. Fenner was unable to do so and performed infection tests on laboratory rabbits.
When they tested the prevalent viral lineages in the 1950s, they found that they were less lethal than the initial virus, Dr. Fenner’s findings. And the death rate was relatively low in the 1990s.
But then things changed.
New viral lineages killed more laboratory rabbits. And they often did it in a new way: by shutting down the animal’s immune system. Bacterial intestines in rabbits, usually harmless, multiplied and caused deadly infections.
“It was really scary when we saw that,” Dr. Read on
Oddly enough, wild rabbits in Australia don’t have Dr. Read the animals in the lab. He and his colleagues suspect that the new virus adaptation was a response to stronger rabbit defenses. Research has shown that Australian rabbits have acquired new mutations in the genes involved in the first line of disease defense, known as their own immunity.
As rabbits develop stronger inherent immunity, Dr. Read and his colleagues suspect that natural selection, in turn, favored viruses that could overcome this defense. This evolutionary arms race eliminated the advantage that wild rabbits briefly enjoyed. But these viruses were even worse against rabbits that did not develop this resistance, such as Dr. Read the lab.
And the arms race is still going strong. About a decade ago, a new lineage of myxoma virus emerged in South East Australia. This branch of lineage C is evolving much faster than other lineages.
Infection experiments suggest that with new mutations, Lineage C is doing a better job of getting from host to host, Dr. Read and his colleagues, which has not yet been published in a scientific journal. Many infected rabbits show a strange form of myxomatosis, and develop severe inflammation in the eyes and ears. In fact, mosquitoes like to drink blood in those places, and the virus may be more likely to reach a new host.
Virologists see some important lessons that myxoma virus can provide as the world struggles with the Covid pandemic. Both diseases affect not only the genetic composition of the virus, but also the host’s defenses.
As the pandemic continues for the third year in a row, people are more protected than ever from the immunity created by vaccines and infections.
But coronavirus, like myxoma, has not gone the inevitable way to warmth.
The Delta variant, which originated in the United States last fall, was more lethal than the original version of the virus. It was replaced by Delta Omicron, which caused less serious illness to the average person. But virologists at the University of Tokyo have conducted experiments that suggest that the Omicron variant is evolving into more dangerous forms.
“We don’t know what the next step in evolution will be,” Dr. Katzourakis warned. “This chapter on the evolutionary path of mischief is yet to be written.”