UNIVERSITY PARK, Pennsylvania – A common misconception is that viruses become milder over time as they become endemic within a population. However, new research, led by Penn State and the University of Sydney, reveals that a virus – called myxomatosis – that infects rabbits has become more deadly over time. The findings highlight the need for stringent surveillance of human viruses, including SARS-CoV-2, monkeypox and polio, to increase virulence.
“During the COVID-19 pandemic, a lot of people incorrectly assumed that with the outbreak of SARS-CoV-2, it would also become milder,” Reed said. “However, we do know that the delta variant was more contagious and caused more serious disease than the original strain of the virus, and omicron was more transmissible than delta. Our new research shows that the rabbit virus has evolved to be more lethal, and there is no reason why this could not happen with SARS- CoV-2 or other viruses that affect humans.”
According to Read, myxomatosis was introduced to Australia in the early 1950s to suppress out-of-control non-native rabbit populations. Known as ‘myxoplasmosis,’ is the disease it caused, resulting in swollen and fluid-filled skin lesions, swelling of the head and eyelids, drooping ears, and obstruction of the airways, among other symptoms. The virus was so lethal that it killed an estimated 99.8 percent of the rabbits it infected within two weeks.
However, over time, the virus became milder, killing only 60% of infected rabbits and taking longer to do so.
“Scientists at the time believed that this finding was inevitable,” Reed said. “What they called the ‘law of virulence reduction’ indicates that viruses naturally become milder over time to ensure that they do not kill their hosts before they have a chance to pass on to other individuals.”
However, when Reed and his team began studying rabbit myxoma virus in 2014, they found that the virus had regained the upper hand and was once again killing rabbits at a higher rate. In their latest study, published October 5 in the Journal of Virology, they examined several variants of myxomavirus collected between 2012-2015 in the laboratory to determine their virulence. The team determined that viruses fall into three strains: A, B, and C.
Interestingly, Reed said, the rabbits in their study showed different symptoms than those caused by viruses collected in the first decades after release.
“Instead of developing swollen, fluid-filled lesions, these rabbits developed flat lesions, indicating a lack of a reduced immune response,” Reed said. In addition, these rabbits had a higher number of bacteria distributed in multiple tissues, which is also consistent with immunosuppression. We interpreted this ‘amyxomatous’ phenotype as an adaptation by the virus to overcome the evolved resistance in the wild rabbit population. “
However, the c lineage produced a slightly different response in rabbits. C-infected rabbits had significantly greater swelling at the base of the ears and around the eyelids, where mosquitoes usually bite. These areas also contain very high amounts of viruses.
“Insect transmission depends on the presence of large amounts of virus in locations easily accessible to the vector,” Reed said. “We hypothesize that c-lineage viruses are capable of enhanced dissemination to sites around the head where mosquitoes are likely to feed and that they are able to suppress inflammatory responses at these sites, allowing sustained virus replication in large quantities.”
Reed said the team’s findings show that viruses do not always evolve to be milder.
“By definition, an evolutionary arms race occurs when organisms evolve adaptations and counter-adaptations against one another,” Reed said. “With myxomatosis, the virus has developed new tricks, resulting in increased rabbit mortality. However, over time rabbits are likely to develop resistance to these tricks. A similar arms race may occur with SARS-CoV-2 and other human viruses as it becomes Humans are more immune. That is why it is so important for vaccine manufacturers to keep abreast of the latest changes and for the public to stay up to date on their vaccines. Even better is to develop a universal vaccine that works against all variants and is effective for a longer period of time.”
The other authors of the paper are Peter Kerr, formerly of CSIRO Health and Biosecurity, who is now deceased. Isabella Catadori, Professor of Biology, Penn State; Derek Sim, Associate Research Professor of Biology, Penn State; John Liu, Postdoctoral Researcher, CSIRO Health and Biosecurity; and Edward Holmes, Professor of Medicine and Health, University of Sydney.
This research was supported by the National Institute of Allergy and Infectious Diseases, which was initially stimulated by an initial grant from the Huck Institutes of Life Sciences in Pennsylvania.
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