Angel Tam Genomics provides powerful tools in the global effort to combat Severe Acute Respiratory Syndrome SARS Angel Tam Biochem 118Q Spring 2003 Professor Doug Brutlag Angel Tam Genomics provides powerful tools in the global effort to combat Severe 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 on the cots until every bed is full yet others crowd in Their faces soon wear a bluish cast a distressing cough brings up blood stained sputum In the morning 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 Spanish Influenza a devastating pandemic that infected 20 to 40 percent of the global population and killed over 20 million people in 1918 National Vaccine Program Office The Spanish Influenza was frightening because of its unknown origin In March of 2003 when a mysterious disease called Severe Acute Respiratory Syndrome SARS began to gain worldwide attention many feared that an epidemic reminiscent of the Spanish Influenza 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 a nonproductive cough and shortness of breath Eventually some died because of progressive respiratory failure By mid April of 2003 there were over 4300 cases of SARS worldwide and 250 reported deaths in over 25 countries Rota et al In response to the emerging disease the World Health Organization WHO organized a global collaboration to identify the cause of SARS and to find cures for it Progress came quickly By the third week of March 2003 labs in the United States Canada Germany and Hong Kong had identified a novel coronavirus from SARS patients Within the next Angel Tam month this virus was completely sequenced The genomic information proved to be quite powerful in the search for improved diagnostic tests and cures for SARS Discovery and sequencing of SARS CoV One of the first steps in fighting a new disease is to determine its cause To see if SARS was caused by a bacteria virus or other agents researchers obtained blood sputum and bronchial tissues from SARS patients and introduced them into cultures of Vero cells monkey kidney cells When these infected Vero cells started showing signs of death they were observed under an electron microscope This revealed black dots of genetic material inside spirally viruses which clustered along the cell surface and at the endoplasmic reticulum Grady and Altman These images fit the description of a class of virus known as coronaviruses which are known to cause approximately 20 to 30 percent of common colds in humans Lovgren Since the virus isolated from SARS patients was not identical to any known coronavirus scientists gave it a new name SARS CoV It was surprising that a coronavirus was associated with SARS because even though coronaviruses are known to cause serious diseases in animals they are only known to cause mild colds and gastrointestinal problems in humans Coronaviruses belong 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 are the mammalian viruses and group 3 is the avian viruses All coronaviruses have genomes made of a single strand plus sense RNA approximately 30 kb long which is the largest genome of any RNA virus Rota et al Angel Tam After SARS CoV was isolated the next step was to extract and sequence its RNA On April 13 2003 the Genome Science Center at the BC Cancer Agency in Vancouver successfully sequenced the entire genome of SARS CoV from a sample taken from a SARS patient in Toronto Marra et al One day later researchers at the Centers for Disease Control in Atlanta also completed their genetic sequencing using a sample from a SARS victim in Hanoi Vietnam The sequences produced in the two studies differed by only 8 nucleotides Holmes and Enjuanes Since then many labs have also sequenced strains of the virus Figure 1 Analysis of the SARS CoV genome revealed that it has all the common characteristics of a coronavirus but it also has unique features that place it in a group separate from all previously known coronaviruses Knowing the genomic sequence of the SAR CoV is crucial to understanding the molecular characteristics of the virus Genomics provide a wealth of information that can aid in 1 identifying the origin of the virus 2 improving diagnostic tests 3 studying the pathogenesis of the virus and developing treatments for the disease Tracing the origin of SARS Data from the sequencing of SARS CoV suggested that it probably did not result from a recombinant event between the known coronavirus strains Other than one motif located in the 3 UTR short untranslated region there was also no indication of any exchange of genetic material between the SARS virus and non coronaviruses Marra et al Given the wide variety of coronaviruses found in humans it was also possible that SARS CoV evolved from a previously benign human coronavirus But researchers later rejected this hypothesis citing evidence that antibodies to SARS CoV were absent in Angel Tam those that were not infected with the virus which would not have been the case had there been a closely related predecessor in humans Marra et al In a review article in Science leading coronavirologists Kathryn V Holmes and Luis Enjuanes 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 coronavirus genome without affecting its infectivity Holmes and Enjuanes This led them to believe that SARS CoV had probably evolved from an animal virus that recently developed the ability to infect humans Their hypothesis was correct in May of 2003 scientists found a similar strain of the SARS virus in civet cats in mainland China Improvement of diagnostic tests To control the spread of the SARS virus sensitive and specific diagnostic tests are needed to quickly identify potential SARS cases Currently diagnosis in the East and Southeast Asia regions is based on a clinical case definition that includes travel to specific locations or exposure to sick contacts McIntosh
View Full Document
Unlocking...