Proteome of SARS Patients Revealed
By Jason Socrates Bardi
A little more than two years ago, an as-yet-unnamed infection was brewing in Guangdong, China, a remote region in the south of that country. This infection, caused by a novel coronavirus that had never before infected humans, would soon erupt into an epidemic, infecting thousands, killing hundreds, and making dust masks a fashion statement from Hong Kong to Toronto.
By the spring of 2003, media outlets worldwide were reporting on the disease caused by this virus—severe acute respiratory syndrome (SARS)—and before it was contained by that summer, the virus quickly spread to more than two dozen countries, infected some 8,000 people, and claimed nearly 800 lives.
In the wake of the containment of the disease, many scientists worldwide have contributed their efforts to understand the SARS virus and to find new ways of treating SARS infections. In the last many months, the complete genome sequence of the SARS coronavirus has been solved, along with the three-dimensional structures of the virus's main protease enzyme and its receptor protein.
Similarly, an effort to find pharmaceuticals and other compounds that might be effective against the SARS virus was undertaken by a team of scientists at The Scripps Research Institute in La Jolla, California, and at Academia Sinica in Taiwan. Led by Scripps Research Professor Chi-Huey Wong, who holds the Ernest W. Hahn Professor and Chair in Chemistry and is a member of The Skaggs Institute for Chemical Biology at Scripps Research, this team found about 50 compounds out of this library of 10,000 that at reasonable concentrations offered cells some protective effect against the SARS virus.
Now the same group is reporting their latest efforts towards understanding SARS in a recent issue of the journal Proceedings of the National Academy of Sciences. There, the team, this time led by Yu-Ju Chen of Academia Sinica in Taiwan, describes a first glimpse of the proteome of SARS patients.
Chen, Wong, and their colleagues took blood samples from 40 SARS patients that were provided by the Centers for Disease Control in Taiwan and analyzed these samples with the standard proteomic techniques of two-dimensional gel electrophoresis and mass spectrometry. Two-dimensional gel electrophoresis allowed them to separate out the proteins in the patient's blood, and mass spectrometry allowed them to rapidly analyze them. By comparing the samples to uninfected controls, the team was able to determine the changes that take place in the bloodstream upon infection with the SARS virus.
More than 38 proteins showed changes—mostly becoming more abundant in the bloodstream upon infection. This is a lot for an infection with the virus like the one that causes SARS, says Wong. "It's striking how many changes occur in a very short period of time," he says.
In the scientists' report, they detail possible roles that these proteins may play in the pathogenesis of SARS, and they highlight the detection of one of the proteins that is overexpressed—an oxygen radical scavenger called peroxiredoxin II, which is responsible for the removal of toxic hydrogen peroxide in the cytosol of cells.
Significantly, peroxiredoxin II, an intracellular protein, had never before been detected in human blood using two-dimensional gel electrophoresis. The existence of a unique human biomarker upon infection with the SARS virus holds significance for the development of new diagnostic methods for detecting SARS infections and for designing new therapies for SARS patients.
The article, "Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry" by Jenn-Han Chen, Yu-Wang Chang, Chen-Wen Yao, Tzong-Shi Chiueh, Su-Chin Huang, Ko-Yi Chien, An Chen, Feng-Yee Chang, Chi-Huey Wong, and Yu-Ju Chen was published by the Proceedings of the National Academy of Sciences on December 7, 2004. Subscribers to the journal can access the article online at: http://dx.doi.org/10.1073/pnas.0407992101.
For more general information on SARS see: http://www.cdc.gov/ncidod/sars/ and http://www.who.int/csr/sars/en/.
Send comments to: jasonb@scripps.edu
