Overcoming Barriers: How Rabbit Myxoma Virus Leaps into New Species

Viruses are among the most kaleidoscopic entities in nature, constantly mutating and acquiring new properties

In a new study published in the journal mBio, Masmudur Rahman and his Arizona State University colleagues joined an international team of researchers to investigate one such spillover event, myxoma virus (MYXV) from Europe Rabbit crosses to the species of the Iberian hare

The study describes M159, a viral protein known as a "host range factor," a gene recently discovered by chance in myxoma viruses

The researchers hope to better understand these genomic shifts, as spillover events have profound implications for both human and animal health

Understanding the subtle changes that enable viruses to make species jumps may help better prepare for outbreaks of new diseases, limit their spread, and may allow researchers to overcome the viral mechanisms that set the stage for spillover events

In addition to its importance in the study of host-pathogen co-evolution, myxoma viruses have also been studied for their remarkable ability to target and kill human cancer cells without harming normal healthy cells

The new study shows that the M159 protein not only enables MYXV-tol to cross the species barrier and infect hares, but it also appears to help the strain replicate better in human cancer cells, potentially improving the role of MYXV as an anticancer agent

The M159 protein is a member of the poxvirus c7-like host range factor

Rahman is a researcher at Arizona State University's Center for Biological Design of Immunotherapy, Vaccines and Viral Therapeutics

professional killer

When studying the mechanisms of virus cross-species barrier capabilities, researchers rely on model organisms

MYXV belongs to the poxvirus family, a very large group of double-stranded DNA viruses that includes many benign members, as well as the virus that once caused the notorious deadly disease smallpox

Many kinds of viruses have the potential to spill over

Although the natural host of the MYXV virus is the Sylvia Rabbit (known in the Americas as cottontail rabbits), it has been shown that the European rabbit population exposed to the virus has a 99% mortality rate, and that the virus affects European rabbits The host did not have any further adaptations

In the long term, strategies to control rabbits with MYXV have failed because evolutionary selection pressures acting on both the virus and the host have resulted in resistance to MYXV and attenuated viral mutation in rabbits

"Every time a virus jumps from one host to another, we gain a new understanding of nature," McFadden said

New viruses are being blocked

Evidence suggests that chronic exposure of Iberian hares to MYXV or similar viruses has not resulted in outbreaks of myxomatosis since at least the 1990s

Among the genes found in the MYXV-Tol variant is one that encodes a protein called M159
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The new study explores how this single protein might be responsible for MYXV-Tol's species-hopping ability
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The researchers examined laboratory cell lines in rabbits, rabbits and humans exposed to MYXV variants with and without the M159 protein, respectively
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The strain containing the new protein was not very infective to European rabbit cells, while the strain containing M159 was very infective to European rabbit cells, while the strain without the protein was not very infective to European rabbit cells , suggesting that M159 is a key component of MYXV cross-species
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The study also tested two human cancer cell lines that are normally resistant to MYXV, exposing them to an enhanced version of m159
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The results were dramatic
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Human pancreatic cancer and melanoma cells are often semipermissive or nonpermissive to MYXV, which means that the virus typically replicates poorly in these cell types
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However, when the M159 protein was inserted into the MYXV-lau strain, viral replication was significantly enhanced in both cancer cells, suggesting that the protein could be used to improve MYXV as an anticancer drug against certain human tumors
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Further studies are expected to reveal highly pathogenic MYXV-Tol variants and elucidate the mechanisms by which other poxviruses spread to new animal species, including humans
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