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Out of China: SARS virus' genome hints at independent evolution

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12:02pm, April 23, 2003
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The newly deciphered genome of the pathogen responsible for severe acute respiratory syndrome (SARS) suggests that the virus is the product of a long and private evolutionary history.

Since emerging from southern China in February, SARS has struck at least 4,000 people worldwide and killed more than 200. Disease researchers have launched a massive effort to understand the pathogen and control the epidemic.

On April 16, European scientists announced that they had demonstrated that the agent responsible for SARS is a coronavirus never detected before the current outbreak. In experiments on monkeys at the Erasmus Medical Center in Rotterdam, the Netherlands, researchers showed that the new coronavirus alone can cause SARS. Earlier in the outbreak, a member of a separate viral family was also a suspect (SN: 3/29/03, p. 198: Available to subscribers at Morbid Mystery Tour: Epidemic from China is encircling globe).

On April 12, researchers at the British Columbia Cancer Research Centre in Vancouver reported that they had completely sequenced the virus' genome.

Scientists in the United States presented nearly identical findings on April 14. Chinese researchers also sequenced the SARS virus and found that some samples differ considerably from those decoded in North America, which suggests that the virus mutates rapidly.

Comparisons among the newly sequenced genome and other coronaviruses' genomes indicate that SARS virus doesn't belong to any of the three known clusters of related coronaviruses. The 10 coronaviruses that infect mammals fall into two clusters, each of which contains one virus that causes colds in people. The third cluster contains two bird pathogens.

Coronaviruses readily swap genetic material with each other in a process known as recombination. This creates new viruses that share some genetic similarities with each parent virus and occasionally have novel capabilities to cause disease or to infect different hosts.

The largest SARS-virus gene, which makes up a whopping two-thirds of the pathogen's genome, appears to be distantly related to the corresponding gene in a mouse coronavirus. Another region of the SARS genome shares a few similarities with the avian coronaviruses.

Those observations suggest that recombination may have given rise long ago to an ancestor of SARS virus, says Michael M.C. Lai, a virologist at the University of Southern California in Los Angeles. If recombination had occurred more recently, the genetic similarities would be more striking, he says.

By itself, Lai notes, "recombination was not responsible for [SARS virus' recent] emergence as a human pathogen."

The SARS virus may have long had the capacity to infect people but only recently encountered conditions that facilitated its spread, says virologist Shinji Makino of the University of Texas Medical Branch in Galveston. Alternatively, it may have derived from one or more unidentified animal coronaviruses that only recently mutated or recombined to create a human pathogen, he says.

The new pathogen "is very likely from a wild animal," argues Lai. Future investigations in the region of China that seems to harbor the virus might eventually turn up the mysterious animal host, he says.

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