A virus affecting rabbits has become more deadly over time, according to new research.
The findings highlight the need for rigorous control of human viruses, including SARS-CoV-2, monkeypox, and polio, to increase virulence.
A common misconception is that viruses become milder over time as they become endemic within a population.
“During the COVID-19 pandemic, many people have incorrectly assumed that as the SARS-CoV-2 virus becomes endemic, it will also become milder,” says Andrew Read, director of the Huck Institutes for Life Sciences. at PennState.
“However, we know that the Delta variant was more contagious and caused more severe illness than the original strain of the virus, and Omicron is even more transmissible than Delta. Our new research shows that a rabbit virus has evolved to become more deadly, and there is no reason why this cannot happen with SARS-CoV-2 or other viruses that affect humans.”
The rabbit virus, called myxoma, was introduced to Australia in the early 1950s to quell an out-of-control non-native rabbit population. Known as “myxomitis,” the disease it caused caused swollen, fluid-filled skin lesions, swollen heads and eyelids, droopy ears, and blocked airways, among other symptoms. It was so deadly that it killed approximately 99.8% of the rabbits it infected within two weeks.
Over time, however, the virus became milder, killing only 60% of infected rabbits and taking longer to kill.
“Scientists at the time believed this outcome was inevitable,” says Read. “What they called the ‘law of declining virulence’ suggested that viruses naturally become milder over time to ensure they don’t kill their hosts before they’ve had a chance to spread to other people.”
However, when Read and her team began studying myxoma in rabbits in 2014, they found that it had regained the upper hand and was once again killing rabbits at a higher rate.
In the current study, published in the Journal of Virology, the researchers examined several variants of the myxoma virus collected between 2012 and 2015 in the laboratory to determine their virulence. The team determined that the viruses fell into three lineages: a, b, and c.
Interestingly, the rabbits in their study exhibited different symptoms than those induced by viruses collected in the first few decades after release, Read says.
“Instead of developing swollen, fluid-filled lesions, these rabbits developed flat lesions, suggesting a lack of reduced immune response. Furthermore, these rabbits had significantly more bacteria distributed in multiple tissues, which is also consistent with immunosuppression.
“We interpret this ‘amyxomatous’ phenotype as an adaptation of the virus to overcome evolving resistance in the wild rabbit population.”
However, lineage c produced a slightly different response in rabbits. Rabbits infected with lineage c had significantly more swelling at the base of the ears and around the eyelids, where mosquitoes often bite. These areas also contained extremely high amounts of virus.
“Insect transmissibility depends on the presence of large amounts of virus at sites accessible to the vector,” says Read. “We hypothesized that lineage c viruses are capable of further dissemination to sites around the head where mosquitoes are most likely to feed and that they can suppress inflammatory responses at these sites, allowing persistent virus replication in large quantities”.
The team’s findings show that viruses don’t always evolve to become milder, Read says.
“By definition, an evolutionary arms race occurs when organisms develop adaptations and counter-adaptations with each other,” says Read. “With myxoma, the virus has developed new tricks, which are resulting in higher rabbit mortality. However, over time, rabbits are likely to develop resistance to these tricks.
“An analogous arms race with SARS-CoV-2 and other human viruses may be occurring as humans become more immune. That’s why it’s so important for vaccine manufacturers to keep up with the latest variants and for the public to stay up to date on their vaccines. Better still would be to develop a universal vaccine that works against all variants and is effective for a longer period of time.”
Additional co-authors are from the University of Sydney and Penn State. The National Institute of Allergy and Infectious Diseases supported the work.