A Canadian study conducted at Robarts Research Institute sheds new light on how poxviruses can jump from species to species -- and will lead to further exploration of another potential candidate in the emerging field of “oncolytic viruses” to fight cancer.
Poxviruses, the largest and most complex viruses known, have been known about for centuries - the characteristic "pocks" produced by variola virus (Smallpox) giving their name to all forms of infectious disease "a dose of the pox". Smallpox first appeared in China and the Far East at least 2000 years ago.
Researchers have long known that some animal cells could be infected with specific viruses while others could not: Is this protection due to certain receptors on the surface of host cells? Or is it protection conferred from within the cell?
In a paper published on Oct. 24 in Nature Immunology, Robarts scientist Dr. Grant McFadden describes how mouse cells can be experimentally altered to be susceptible to what is normally a rabbit-specific poxvirus. This study provides the first evidence that it is the signaling environment within the cell that determines whether a given host species will be infected or not by this family of viruses.
The research team -- which includes lead author Dr. Fuan Wang from the McFadden lab and collaborators from Dr. Skip Virgin’s lab at Washington University in St. Louis -- has shown that myxoma, a poxvirus lethal only to rabbits, can jump species and infect immune-deficient mice that are disrupted in a set of intracellular signals called the interferon pathway. This particular pathway forms an important part of the innate immune system in vertebrates and differs slightly between species to protect from viral attacks.
Understanding precisely how viruses like myxoma disable a host cell not only helps explain how viruses move into other species but offers the possibility of using the virus to kill human cancer cells. Many cancer cells also have deficiencies in the interferon pathway, which makes them prime targets for oncolytic viruses. Among those viruses under study as oncolytic agents are: herpes simplex virus, adenovirus and vesicular somatitis virus.