The study, published in the January issue of the Journal of Virology, sheds light on the SARS coronavirus, a deadly form of pneumonia caused by the same viral family as the common cold. By tracing its evolutionary history, researchers theorize that SARS is likely the result of a rare recombination of viruses from both mammalian and avian hosts. This, they believe, forms an entirely new virus unrecognizable to human immune systems.
Understanding the evolution of SARS is a crucial step towards managing future viral outbreaks, according to the study's co-author David Guttman, a professor of evolutionary genomics in the Department of Botany. Identifying the specific evolutionary changes that enables this virus to spread into the human population should dramatically improve our understanding of why this particular virus is so virulent. "This will allow us to design more effective treatments and respond more effectively to future outbreaks," says Guttman.
In their study, Guttman and PhD student John Stavrinides deconstructed and compared the SARS virus genome to related coronaviruses using phylogenetic computational tools. They found that the protein encoded on the genome's left side was of mammalian origin (such as cats, cows and mice); while the proteins on the right were of avian origin (such as chickens and ducks). The middle gene - the S gene - encodes a protein that is a mix of mammalian and avian-like viruses.
In all coronaviruses, the S gene encodes a protein called spike glycoprotein, which protrudes from the head of the virus. With most coronaviruses, the immune system would recognize this protein as a foreign molecule. However, the merging of mammalian and avian viruses very likely altered the structure of this protein and allowed it to sneak past immune surveillance.
Guttman says this type of genetic change can have far more dramatic consequences than simple genetic mutations, in which only small features in genes are changed at any one time. "These recombination events have the potential to create an entirely new structure essentially instantaneously," he says. "Since our immune systems have never seen this new viral form, it is more difficult for them to respond to it in a timely and effective manner." Similar genetic exchange events are believed responsible for some of the most devastating viral epidemics and pandemics, such as the 1918 Spanish Influenza pandemic that killed over 20 million people worldwide.
In 2002, SARS spread to over 30 countries within six months and killed over 700 people. It is believed the virus was transmitted to humans by masked palm civets (an animal related to ferrets and cats) in the food markets of southern China. What is not known, however, is exactly what event led to the evolution of this new virus.
"It's possible that a civet picked up the virus from a bird," says Guttman. "This could have created the opportunity for a very rare recombination event that produced a virus with a new host range. Basically, the recombinant virus is infectious to humans, while the two parent viruses are not. This new virus likely then spread to humans due to poor hygiene and close quarters in the food markets of Southern China."
Although there have been promising developments in SARS vaccine research, a truly effective vaccine is probably years away. "We hope that this work will contribute to the design of specific and effective vaccines," says Guttman, "but perhaps it will be most useful in the development of tests for the diagnosis of new SARS outbreaks. We will be in a much better position to recognize new and potentially deadly viral outbreaks if we can identify the specific evolutionary changes that made SARS so deadly." Guttman states that this is just a first step in this process, and that real progress will require a more thorough understanding of viruses existing in animal populations, and how these viruses are transmitted to humans.
The study received funding from the Natural Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation.
Department of Botany
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