How the Rabbit Myxoma Virus Retaliased the Species Barrier

How the Rabbit Myxoma Virus Retaliased the Species Barrier ...

Viruses are among the most protean entities in nature, slowly mutating and acquiring new characteristics. These tiny entities follow a simple and relentless imperative: infect as many host organisms as possible. Occasionally, a virus genomic alteration permits it to leap from one species to another, in a process known as spillover.

In new research published in journalmBio, Masmudur Rahman and his Arizona State University colleagues have joined international researchers to investigate one of the spillover events, including when the Myxoma virus (MYXV) transformed a species from European rabbits to Iberian hares.

M159, a viral protein called a host range factor that arose very recently through a fortuitous gene pickup in the myxoma virus, has enabled the virus to expand its existing host range, traversing the species barrier, and causing lethal disease in Iberian hares.

Researchers wish to understand these genomic transitions, as spillover events have profound implications for both human and animal health. One recent event, caused by mutations in a novel, SARS-like virus of unknown origin, is responsible for the global epidemic of COVID-19 disease, which has killed over five million people worldwide.

Understanding the subtle changes that may allow viruses to make jumps might aid in preparing for new diseases, limit their transmission, and possibly allow researchers to outwit viral mechanisms that enable spillover events. Human-engineered therapies against pathogens (including viruses) are part of a never-ending arms race between infectious agents and their host organisms.

The myxoma virus has been investigated for its ability to target and kill human cancer cells, while also leaving their normal healthy cells unharmed. It is a number of the most promising viruses available in the new field of virotherapy, which involves cancer fighting or oncolytic drugs, including myxoma.

The M159 protein has suggested that it would not only infiltrate MYXV-Tol''s barrier, but also aid in the replication of human cancer cells, thus potentially improving MYXV as a cancer-fighting agent.

M159 is a member of the poxvirus C7-like host range factors. In the future, identifying the proteins that interact with M159 in hares and human cancer cells will help us understand whether M159 is compatible with similar or different signaling techniques, according to Rahman.

Rahman is joined byGrant McFadden, the director of the center, and byArvind Varsani, an expert in the Biodesign Center for Fundamental and Applied Microbiomics. McFadden, Varsani, and Rahman are among the ASU''s most recent authors. Ana Agueda-Pinto, SimonaKraberger, AmiGutierrez, and Honor L.Glenn have all been featured in this video.

Researchers from Universidade do Porto, Vairao, Portugal, Universidade de Oviedo, Campus El Cristo, Oviedo, Spain, and the International Journal of Justice, the CIAG del Chaparrillo, the Ciudad Real, Spain are among the collaborators.

Specialized killer

Researchers are relying on model organisms to investigate the mechanisms that influence viruses'' ability to cross species barriers. The Myxoma virus is a particularly beneficial candidate for such experiments and is the most extensively investigated field model for this type of study. This fact is due to a historical event in which MYXV was used to control populations of European rabbits beginning in 1950.

MYXV belongs to the poxvirus family of viruses, a large assemblage of double-stranded DNA viruses that includes many minor members, as well as the virus that once caused the notoriously deadly smallpox disease.

Many kinds of viruses have a potential spillover. Influenza outbreaks are the result of spillover events that, in turn, feed birds, as reservoirs for the virus, spread the disease to other species, including ducks, chickens, and pigsand humans. Mutating strains gain new abilities to aid their transmission and ability to avoid host immune defenses.

Although the MYXV virus''s natural hosts are Sylvilagus rabbits (also known in the Americas as cottontails), exposure of European rabbit populations to this virus proved 99% fatal, without any further adaptation of the virus to the European rabbit host. Myxomatosis is a highly contagious rabbit disease that has been discovered in rabbit populations by fleas or mosquitos. MYXV-Tol is a common lethal disease in hares.

Long term, the rabbit control strategy with MYXV failed, as evolutionary pressures acting on both the virus and the host resulted in MYXV-resistant rabbits and attenuated viral variants. Nevertheless, MYXV is a valuable laboratory tool for the study of the poorly understood dance between infectious agents and the molecular transformations used by species to thwart them.

Every time a virus leaps from one host species into another, we learn something new about Mother Nature, according to McFadden. In the case of MYXV-Tol, the acquisition of a single new virus gene allowed this new strain to have access to a new host species previously resistant to the virus.

New virus on the block

An altered virus strain called MYXV-Tol appeared out of nowhere, despite a few exceptions. The same strain had acquired a small number of new genes, which it was acquired through recombination with an as-yet-unidentified poxvirus. The result was a supercharged strain that proved both infectious and fatal to hares starting in the autumn of 2018.

A single protein identified in the MYXV-Tol variant was discovered, according to a research. M159 is a possible culprit in MYXV-Tols species-hopping capacity. The researchers studied laboratory cell lines of rabbit, hare, and human individuals exposed to MYXV variants with and without the M159 protein.

Despite the fact that M159-containing strains were not more infectious to European rabbits, M159-containing strains now were quite infectious to European hares, whereas M159 was not the main ingredient in allowing MYXV to cross the species barrier.

Two human cancer cell lines that are normally resistant to MYXV were tested and the M159-enhanced version was significantly enhanced. However, when the M159 protein was inserted into the MYXV strain, viral replication in both cancer cell lines was significant enhanced, suggesting that the protein might be used to improve MYXV as a cancer-fighting agent.

Further research intends to shed new light on the highly pathogenic MYXV-Tol variant as well as highlight the mechanisms used by other poxviruses to spill over into new animal species, including humans.

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