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Updated 10:00 AM October 13, 2003



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SARS virus changes can present challenges

The SARS virus is capable of changing rapidly and unpredictably, which could present serious challenges for managing the disease and developing drugs and vaccines to combat it, research at U-M suggests.

Ever since the SARS virus suddenly appeared in humans, scientists have been speculating about its origins and relationships to other, similar viruses. Using evolutionary analysis of protein sequences, researchers have concluded that the SARS virus represents a different and previously little-known lineage that has undergone some recombination, a process that can shuffle genes or gene regions among different viral lineages. This shuffling process provides genetic variation, which makes viruses more adaptable and can help them survive and adapt in new hosts, evade immune responses and become resistant to drugs. The results appear in the September issue of the journal Infection, Genetics and Evolution.

U-M researchers have concluded that the SARS virus represents a different and previously little-known lineage.

The virus associated with SARS (known as SARS-CoV) is a type of coronavirus, so named because of the crown of spikes on its surface. Coronaviruses are divided into three categories: group one has been found in primates, carnivores, and the group of animals that includes cattle, pigs and deer; group two occurs in that same group of animals as well as in rodents, birds and animals in the group that includes horses, tapirs and rhinos; group three has been found only in birds. Previous evolutionary analyses have suggested that the SARS virus is equally, but distantly, related to the three coronavirus groups.

Graduate student Joshua Rest and associate professor David Mindell, both of the Department of Ecology and Evolutionary Biology, used a technique that detects recombination by analyzing the gene for a protein known as RNA dependent RNA polymerase (RDRP). In their analysis, one end of the RDRP gene appeared most closely related to group 3 coronaviruses, but the other end appeared distantly related to all three groups, suggesting that the RDRP gene in SARS-CoV had been cobbled together from parts of RDRP genes taken from different coronavirus lineages sometime in the past.

"Our results do not mean that human infection by SARS-CoV is linked to the particular recombination event for which we found evidence," Mindell says. "But demonstration of recombination in the SARS-CoV lineages does indicate its potential for rapid, unpredictable evolutionary change, and this is a potentially important challenge for public health management and for drug and vaccine development."

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