Round-table discussion on newly emerging infectious diseases Chairperson: H. Limited variation in SARS coronavirus S and N protein genes observed by direct sequencing from patients' orginal clinical specimens. The Movies can be viewed with Quicktime. SARS Conference. These efforts resulted in two intriguing observations. Secondly, the presence of N-terminal extensions other than nsp7, such as ubiquitin and His 6 , severely affected the primer extension activity of nsp8 Figure 7 , potentially by changing its oligomeric state Figure 2.
However, the relatively strong activity of nsp Figure 7 , a potential naturally occurring replicase processing intermediate, implies that nsp8's activity is unlikely to be directly controlled by an N-terminal cleavage event, as was observed for, e.
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In addition, these observations suggest that a more diverse array of nsp8-containing RdRps may be involved in CoV replication and transcription. Fourthly and last, we observe that a ratio of nsp7:nsp8 is sufficient to capture all nsp8 in a higher molecular weight complex Figure 2 F whereas previously a ratio was required 13 , potentially due to the additional N-terminal residues that altered the dynamics of complex formation.
The functional implications of these observations are not clear at present, but additional structural studies will likely be required to address these issues in detail, and gain insights that may aid in explaining the in vitro results presented here. In addition, our experiments and controls revealed and address a number of disparities between previous claims and hypotheses 12 , and our own observations. Consequently, it is now a distinct possibility that CoV RNA synthesis involves structurally different and functionally separable RNA synthesising complexes [e. It will therefore be crucial to study whether these different polymerase activities are part of the same enzyme complex and, if so, whether they can influence each other's activity or are subject to additional control mechanisms.
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The molecular biology of SARS coronavirus.
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Molecular Biology of the SARS-Coronavirus
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Processing of open reading frame 1a replicase proteins nsp7 to nsp10 in murine hepatitis virus strain A59 replication.
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Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease.