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Researchers find 'secret weapon' used by SARS virus

In 2003, the highly contagious and often-deadly mystery disease now called SARS emerged explosively out of Southern China. It eventually killed an estimated 916 people in Asia, Europe, and North and South America--nearly one in ten of those it infected.

When scientists identified the virus that caused this sudden acute respiratory syndrome, they classified it as a coronavirus--a virus family whose other members cause many common colds. But to there was nothing common about the lethality of SARS; clearly, this coronavirus had some nasty tricks up its sleeve.

Now, in a discovery that suggests a possible new route by which scientists might fashion a vaccine against SARS, researchers at the University of Texas Medical Branch at Galveston (UTMB) have uncovered one of those tricks: a "secret weapon" that the SARS coronavirus uses to sabotage the immune defenses of infected cells. Experiments conducted by the UTMB scientists show that a SARS coronavirus protein called "nsp1" causes the breakdown of biochemical messages that normally prompt the production of a protein critical to defending the body against viruses.

"The SARS nsp1 protein degrades the messenger RNA instructions sent from DNA to make interferon beta, which is crucial to host immunity," said UTMB professor of microbiology and immunology Shinji Makino, senior author of a paper on the discovery to be published online the week of August 7 in the Proceedings of the National Academy of Sciences. "This is a very rare phenomenon, and it raises a lot of questions -- among them, whether we can make a mutant form of SARS coronavirus that lacks the ability to degrade messenger RNA, which could ultimately lead to the creation of a live attenuated vaccine for SARS."

Although many viruses interfere with host cells making messenger RNA or translating it into infection-fighting proteins, only one other virus is known to break down messenger RNA: herpes simplex virus (HSV).

Makino credits lead author Wataru Kamitani, a UTMB postdoctoral research fellow, with noticing that the nsp1 protein had an unexpected effect while he was investigating a different set of SARS coronavirus proteins. "He found this suppression of host gene expression, and then he designed several elegant experiments that showed it was caused by RNA degradation, something never before seen in an RNA virus."

Exactly how that degradation takes place, how an RNA virus can preserve its integrity when it makes a protein that breaks down RNA, and whether a mutated non-RNA-degrading SARS coronavirus could constitute a workable SARS vaccine are all issues that Makino's group intends to pursue. "The main concern for everybody is whether SARS will come back," Makino said. "We want to be ready for it if it does."

Jim Kelly | EurekAlert!
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