New understanding of how poxviruses jump from species to species

April 01, 2016

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.

Dr. McFadden, Co-Director of the Biotherapeutics Research Group at Robarts in London, Ontario, is a member of the Oncolytic Virus Consortium, led by Dr. John Bell, professor of medicine at the University of Ottawa and senior scientist of Cancer Care Ontario. The consortium aims to bring together clinicians and scientists with an interest in cancer-killing viruses in order to accelerate their findings into the clinic. For his part, Dr. McFadden remains cautious but encouraged about the work ahead.

???This is really the opening of a new door that will likely take years to test and determine which viruses are the best oncolytic candidates,??? said Dr. McFadden, who holds a Canada Research Chair in Molecular Virology and is also professor of microbiology and immunology at The University of Western Ontario. ???A year ago I was interested in immune evasion by poxviruses -- and I still am -- but these unexpected findings on the mechanism of action within the host cell help to answer fundamental questions like: Why do we have species barriers that determine whether cells can or cannot be infected by viruses? And how do some viruses actually cross the species barrier? These fundamental questions have a range of important applications in biology and medicine.???

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