THURSDAY, Jan. 29, 2004 (HealthDayNews) -- Scientists have traced the exact genetic changes that turned SARS from a virus that infected only animals to one that struck thousands of people around the globe.
The findings strengthen the argument that SARS originated in animals and gradually became acclimated to human hosts, says a paper appearing in the Jan. 30 issue of Science.
Perhaps most surprising was the speed with which SARS became comfortable in humans.
"I'm an evolutionist and I usually deal with evolution over the span of anywhere from 1 million to 30 million years. Usually in the span of 10 million years, you get a number of changes [in organisms] that give you enough information about the dynamics," says Chung-I Wu, one of the 51 authors of the study and a professor and chairman of the department of ecology and evolution at the University of Chicago. "The SARS virus does that in a span of three to four months."
The researchers divided the 2002-2003 epidemic into three phases --early, middle and late -- and examined the genetic sequences of 63 SARS samples taken from patients in each stage.
The first phase started in November 2002 with the emergence of 11 apparently independent human cases from different locations in the Pearl River Delta of China's Guangdong province. Viral genomes in these cases were identical to those of the animal hosts. People in the region have recently adopted "culinary habits requiring exotic animals," the authors write, and seven of the 11 patients had had documented direct contact with wild animals.
The second or middle phase began with the first "super-spreader" event, an outbreak at a hospital in Guangzhou beginning Jan. 31, 2003, that resulted in 130 cases, 106 of them acquired in the hospital. An infected doctor at the Guangzhou hospital carried the virus to the Metropole Hotel in Hong Kong on Feb. 21, where he infected several guests. Those guests then carried the virus to Vietnam, Canada, Singapore and the United States.
All the rest of the cases comprise the third or late phase. This was marked by stabilization of the virus as it adapted to its human host.
In the early phase of the epidemic, between November and late January, two main genetic sequences were identified. One had a 29-nucleotide sequence that was missing in later samples, and the other had an 82-nucleotide sequence also absent in later samples. Both these sequences were in a part of the genome known as Orf8. These genotypes matched virus samples taken from animals in a market in Shenzen as well as civet cats in Hubei Province, both in China.
By the middle phase of the outbreak, a separate version of the virus missing the 29-nucleotide sequence was predominating.
In the early phase, the virus was not effectively spreading to humans. "It took them [the virus] a while to accumulate the right mutations to spread in the human population and you can see the signature quite clearly from the DNA sequence," Wu says. "I don't think anybody would have suspected such a dramatic change in the dynamics. It's usually over a span of 10 years that you see the trend from rapid evolution to a sort of stasis, but in this case it happened in such a short period of time."
"In the early phase, the SARS virus evolved very rapidly and, between January and March, it slowed down considerably and stopped evolving, which is a sign that they are adapting to their human host," Wu adds. "They evolved into a comfortable niche very quickly."
Paul Ewald is a professor of biology at the University of Louisville. "The documented evolutionary changes demonstrate how rapidly disease organisms can evolve to become more effective agents of human disease," he says.
The new study, adds Dr. Bruce Polsky, chief of the division of infectious diseases at St. Luke's-Roosevelt Hospital Center in New York City, is mainly an epidemiological tool to see how the virus shape shifted as it moved both geographically and between species. If you analyze a SARS coronavirus from a human, you would then be able to tell if it came from the original animal source.
The information may have some relevance to vaccine developers, Polsky says. "You want to develop a vaccine that is going to recognize all or most of the prevalent strains of an organism circulating in humans," he says.
One remaining question is whether the virus, now settled in humans, will become less virulent even while still causing disease. "There's no evidence of that yet," Polsky says.
More information
For more on SARS, visit the U.S. Centers for Disease Control and Prevention or the World Health Organization.
