Angel TamGenomics provides powerful tools in the global effort tocombat Severe Acute Respiratory Syndrome (SARS)Angel Tam(Biochem 118Q)Spring 2003Professor Doug BrutlagAngel TamGenomics provides powerful tools in the global effort to combatSevere Acute Respiratory Syndrome (SARS)Hundreds of stalwart young men in the uniform of their country [come]into the wards of the hospital in groups of ten or more. They are placed onthe cots until every bed is full yet others crowd in. Their faces soon wear abluish cast; a distressing cough brings up blood stained sputum. In themorning the dead bodies were stacked about the morgue like cordwood.Colonel Victor C. Vaughan described this scene during his visit to Fort Devens,Massachusetts in September, 1918 (Kolata). The young men were victims of the SpanishInfluenza, a devastating pandemic that infected 20 to 40 percent of the global populationand killed over 20 million people in 1918 (National Vaccine Program Office). TheSpanish Influenza was frightening because of its unknown origin. In March of 2003,when a mysterious disease called Severe Acute Respiratory Syndrome (SARS) began togain worldwide attention, many feared that an epidemic reminiscent of the SpanishInfluenza would ensue. Like the Spanish Influenza, SARS caught the world by surprise.SARS was first discovered in Hong Kong, Canada, and Vietnam in early March,2003. Patients had flu-like symptoms such as fever and malaise, which was followed by anonproductive cough and shortness of breath. Eventually, some died because ofprogressive respiratory failure. By mid-April of 2003, there were over 4300 cases ofSARS worldwide and 250 reported deaths in over 25 countries (Rota et al.). In responseto the emerging disease, the World Health Organization (WHO) organized a globalcollaboration to identify the cause of SARS and to find cures for it. Progress camequickly. By the third week of March, 2003, labs in the United States, Canada, Germanyand Hong Kong had identified a novel coronavirus from SARS patients. Within the nextAngel Tammonth, this virus was completely sequenced. The genomic information proved to be quitepowerful in the search for improved diagnostic tests and cures for SARS.Discovery and sequencing of SARS-CoVOne of the first steps in fighting a new disease is to determine its cause. To see ifSARS was caused by a bacteria, virus, or other agents, researchers obtained blood,sputum, and bronchial tissues from SARS patients and introduced them into cultures ofVero cells (monkey kidney cells). When these infected Vero cells started showing signsof death, they were observed under an electron microscope. This revealed black dots ofgenetic material inside spirally viruses, which clustered along the cell surface and at theendoplasmic reticulum (Grady and Altman). These images fit the description of a class ofvirus known as coronaviruses, which are known to cause approximately 20 to 30 percentof common colds in humans (Lovgren). Since the virus isolated from SARS patients wasnot identical to any known coronavirus, scientists gave it a new name: SARS-CoV.It was surprising that a coronavirus was associated with SARS, because eventhough coronaviruses are known to cause serious diseases in animals, they are onlyknown to cause mild colds and gastrointestinal problems in humans. Coronavirusesbelong to family of enveloped viruses that replicate in the cytoplasm of animal host cells.They come in a wide variety, but are divided into three main groups: group 1 and 2 arethe mammalian viruses, and group 3 is the avian viruses. All coronaviruses have genomesmade of a single-strand plus-sense RNA approximately 30 kb long, which is the largestgenome of any RNA virus (Rota et al.).Angel TamAfter SARS-CoV was isolated, the next step was to extract and sequence itsRNA. On April 13, 2003, the Genome Science Center at the BC Cancer Agency inVancouver successfully sequenced the entire genome of SARS-CoV from a sample takenfrom a SARS patient in Toronto (Marra et al). One day later, researchers at the Centersfor Disease Control in Atlanta also completed their genetic sequencing, using a samplefrom a SARS victim in Hanoi, Vietnam. The sequences produced in the two studiesdiffered by only 8 nucleotides (Holmes and Enjuanes). Since then, many labs have alsosequenced strains of the virus (Figure 1). Analysis of the SARS-CoV genome revealedthat it has all the common characteristics of a coronavirus, but it also has unique featuresthat place it in a group separate from all previously known coronaviruses.Knowing the genomic sequence of the SAR-CoV is crucial to understanding themolecular characteristics of the virus. Genomics provide a wealth of information that canaid in: 1) identifying the origin of the virus, 2) improving diagnostic tests, 3) studying thepathogenesis of the virus and developing treatments for the disease.Tracing the origin of SARSData from the sequencing of SARS-CoV suggested that it probably did not resultfrom a recombinant event between the known coronavirus strains. Other than one motiflocated in the 3´UTR (short untranslated region), there was also no indication of anyexchange of genetic material between the SARS virus and non-coronaviruses (Marra etal.). Given the wide variety of coronaviruses found in humans, it was also possible thatSARS-CoV evolved from a previously benign human coronavirus. But researchers laterrejected this hypothesis, citing evidence that antibodies to SARS-CoV were absent inAngel Tamthose that were not infected with the virus, which would not have been the case had therebeen a closely-related predecessor in humans (Marra et al.).In a review article in Science, leading coronavirologists Kathryn V. Holmes and LuisEnjuanes stated that it was unlikely that the SARS virus was genetically engineered,because at present times it would be impossible to modify 50% of the coronavirusgenome without affecting its infectivity (Holmes and Enjuanes). This led them to believethat SARS-CoV had probably evolved from an animal virus that recently developed theability to infect humans. Their hypothesis was correct: in May of 2003 scientists found asimilar strain of the SARS-virus in civet cats in mainland China.Improvement of diagnostic testsTo control the spread of the SARS virus, sensitive and specific diagnostic tests areneeded to quickly identify potential SARS cases. Currently, diagnosis in the East andSoutheast Asia regions is based on a clinical case definition that includes
View Full Document
Unlocking...