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    Home > Biochemistry News > Biotechnology News > Overcoming Barriers: How Rabbit Myxoma Virus Leaps into New Species

    Overcoming Barriers: How Rabbit Myxoma Virus Leaps into New Species

    • Last Update: 2022-05-13
    • Source: Internet
    • Author: User
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    Viruses are among the most kaleidoscopic entities in nature, constantly mutating and acquiring new properties
    .
    These tiny entities follow a simple and relentless command: to infect as many host organisms as possible

    .
    Occasionally, a virus' genome changes to allow it to jump from one species to another, a process known as spillover

    .

    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 resulting hybrid strain, dubbed MYXV-Tol, enables the virus to expand its existing host range, cross species barriers, and cause deadly disease in Iberian hares

    .

    The researchers hope to better understand these genomic shifts, as spillover events have profound implications for both human and animal health
    .
    One such recent event, caused by mutations in a novel SARS-like virus of unknown origin, is responsible for the global COVID-19 pandemic, which has killed more than 5 million people worldwide

    .

    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
    .
    Human-engineered therapeutics against pathogens, including viruses, are part of a never-ending arms race between the source of infection and its host organism

    .

    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
    .
    It is one of the most promising viruses in the new field of viral therapy, which uses anticancer or oncolytic viruses, including myxoma viruses

    .

    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
    .
    In the future, identifying proteins that interact with M159 in rabbit and human cancer cells will allow us to understand whether M159 targets similar or different signaling pathways

    .
    ' Rahman said

    .

    Rahman is a researcher at Arizona State University's Center for Biological Design of Immunotherapy, Vaccines and Viral Therapeutics
    .
    He was joined by Grant McFadden, director of the center, and Arvind Varsani, a researcher at the Center for Basic and Applied Microbiology Biodesign

    .
    McFadden, Varsani and Rahman are also researchers in Arizona State University's School of Life Sciences

    .

    professional killer

    When studying the mechanisms of virus cross-species barrier capabilities, researchers rely on model organisms
    .
    Myxoma virus is a particularly attractive candidate for this type of research and is the most widely studied field model for this type of research

    .
    This fact is due to historical events that began in 1950 with MYXV in Europe and Australia to control European rabbit populations

    .

    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
    .
    For example, annual outbreaks of influenza are the result of spillover events that occur when migratory birds act as virus reservoirs to spread the disease to other species, including ducks, chickens, pigs, and humans

    .
    As viruses spread from one species to another, mutated strains acquire new abilities to help them spread and the ability to evade the host's immune defenses

    .

    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
    .
    The highly contagious virus, which spreads in rabbit populations by fleas or mosquitoes, produces a deadly rabbit disease called myxomatosis

    .
    MYXV-Tol was found to cause a very similar fatal disease in wild rabbits

    .

    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
    .
    However, MYXV provides a valuable laboratory tool for studying the little-known dances between infectious pathogens and the molecular transformations that species use to prevent them

    .

    "Every time a virus jumps from one host to another, we gain a new understanding of nature," McFadden said
    .
    "In the case of MYXV-Tol, we learned that acquiring a new viral gene enabling this new strain of the virus to reach new host species that were previously resistant to the virus

    .
    "

    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
    .
    Then a mutated virus strain called MYXV-Tol popped up

    .
    This new variant showed high similarity to the previously circulating MYXV-Lau virus, with one notable genomic exception

    .
    The new strain gained a new set of genes that were obtained by recombination with a yet-to-be-identified poxvirus

    .
    The result was a super-strong variant that was both contagious and highly lethal to hares living on the Iberian peninsula, killing hundreds of hares starting in the fall of 2018

    .

    Among the genes found in the MYXV-Tol variant is one that encodes a protein called M159
    .
    The new study explores how this single protein might be responsible for MYXV-Tol's species-hopping ability

    .
    The researchers examined laboratory cell lines in rabbits, rabbits and humans exposed to MYXV variants with and without the M159 protein, respectively

    .

    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
    .

    The study also tested two human cancer cell lines that are normally resistant to MYXV, exposing them to an enhanced version of m159
    .
    The results were dramatic

    .
    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

    .
    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

    .

    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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