Summary
Researchers in Rotterdam have positively identified the virus responsible for SARS

Recent reports over the last couple of weeks have claimed that SARS, a new type of highly contagious and occasionally fatal viral pneumonia, may be caused by a paramoxyvirus, maybe by a coronavirus, and maybe by chlamydia. Dutch scientists at Erasmus Medical Center in Rotterdam, the Netherlands today announced that SARS is indeed caused by a novel form of coronavirus never before seen in humans. The World Health Organization (WHO) has confirmed this report. Experiments revealed that monkeys infected with coronavirus develop symptoms similar to those seen in the human syndrome, those that are not infected do not develop the symptoms, and those infected with both paramoxyvirus and coronavirus are no sicker than those infected with coronavirus alone. These criteria are considered to be definitive proof that the newly-identified coronavirus is indeed the causative agent of SARS.

Coronaviruses cause disease in both humans and animals. Although there are only two coronaviruses that infect humans, they are responsible for an estimated 1/3 of all colds. Coronaviruses also cause diseases, some of which are serious, in animals.

The first clinical cases of SARS appeared in China in November of 2002, and only in the past few weeks has SARS attracted international attention. Yet scientists have not only identified the new pathogen, but its genome has been independently sequenced at the University of Hong Kong (report from People's Daily) and at the Centers for Disease Control in Bethesda, MD (CDC SARS information page). The complete SARS virus sequence was published in GeneBank on Tuesday (April 15, 2003). It's astonishing how quickly the research community has been able to identify and characterize this new pathogen.

The SARS coronavirus is formed of 29736 bases of (+)-sense, single-stranded RNA (ssRNA). The virus enters the cell through endocytosis and membrane fusion, and releases mature mRNA into the cytosol, where its first 20 kb is translated into a viral polymerase. The polymerase then creates a full-length (-)-sense strand, that codes for several proteins. The (-)-sense mRNA is then used as a template to create several other monocistronic mRNAs that code for viral proteins. The proteins assemble in Golgi and are exocytosed through the secretory pathway.

Sequencing the genome for SARS has several benefits:

• Although the origin of SARS is as yet unknown, phylogenetic analysis of the sequence indicates that it is a new virus that has not been seen in humans before. Scientists believe that the virus has probably been in an animal population for quite some time, but the original host has not yet been identified.
• Studying the sequence has already lead scientists to believe that there is little or no evidence that SARS is a bioweapon.
• In the short term, having the SARS sequence allows design of sensitive polymerase chain reaction (PCR) tests that can rapidly identify presence of the SARS virus itself. Existing serological tests look for antibodies to the virus, but by the time the antibody titers are high enough to be detected (typically three weeks following the onset of fever), it is often too late for the patient. By contrast, the SARS RT-PCR test should work within the first ten days of onset of fever. A positive PCR test for SARS indicates positively that a patient is infected. A negative test cannot rule out exposure or infection for a variety of reasons. For example, the sample taken from the test may not have contained the virus, or the virus may be suppressed by the host's immune system.
• Knowing the sequence may help researchers to study how the virus is transmitted, to detect the viremia and virus shedding timeline, and to develop effective quarantine strategies.
• In the long term, understanding SARS may help researchers discover a way to combat the disease, or at the very least, to predict who is likely to be at greatest risk. While 96% of SARS patients recover spontaneously, those over 40 or with existing heart or liver disease are most at risk for SARS.

A strange yet oddly entertaining report on coronaviruses is available at Stanford.

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About the Blogger

Mark Johnson is a software developer, trainer, writer, and speaker living in Silver Spring, MD. He works at the National Center for Biotechnology Information, writing documentation and tools for open-source bioinformatics software. He is also president of Elucify Technical Communications (www.elucify.com). He has published dozens of articles on Java component technology, enterprise software development, and XML, and is co-author of the book "Designing Enterprise Applications for the J2EE Platform, Second Edition" (Addison-Wesley 2002). He is currently the author of the monthly Enterprise Java Tech Tips newsletter for Sun Microsystems. Mark has been interviewed on CNN, ITworld.com, and JavaWorld.com, and is a member of the National Association of Science Writers.