Researchers at the Chinese University of Hong Kong joined over 50 scientists from Mainland China and the United States to form the Chinese SARS Molecular Epidemiology Consortium to study the complete evolutionary history of the SARS-coronavirus during last year's SARS epidemic. This project is partially supported by the Hong Kong Research Grants Council. The results of the study are published today in the world renowned scientific journal, Science. This research represents the most extensive molecular epidemiological study of the SARS-coronavirus to-date. A total of 63 SARS-coronavirus genomic sequences isolated from SARS patients infected at various time points, from the beginning until the end, of the epidemic were analysed. The viral genomic sequences were analysed in combination with detailed epidemiological data to map the precise landmarks of the evolution of the SARS-coronavirus.

The study revealed several key findings:

1. Continuous evolution

The analysis revealed that the SARS-coronavirus was mutating continuously throughout the epidemic. The estimated mutation rate of the virus, however, is one-third that of the virus responsible for the acquired immunodeficiency syndrome (AIDS).

2. Active adaptation to the human host

The mutation rate of the virus was most rapid during the early part of the epidemic between the time of the first emergence of SARS to the first major outbreak in Guangdong Province. Thereafter, the mutation rate slowed gradually. The highest rate of mutation is seen in the part of the virus genome coding for the Spike protein, the component of the virus which enables human cell entry. These data suggest that during the early part of the epidemic, the SARS-coronavirus was under significant pressure to change in order to become an efficient human virus.

3. A surprising genotype emerged towards the end of the epidemic

Most of the human SARS-coronavirus sequences differ from the sequences of the coronavirus isolated from Himalayan palm civets by the lack of 29 units of genetic code in one region of the virus. However, a surprising finding of the present study was the isolation of a SARS-coronavirus sequence that had a further deletion of 386 units of the genetic code in the same region of the virus genome. This sequence was initially found in 2 patients who were diagnosed with SARS at the North District Hospital, Hong Kong, in May 2003. The same sequence was subsequently found in a group of 15 SARS patients whose infections were inter-related. This sequence represents the largest truncation in the SARS-coronavirus genome that has been documented to date.

Implications of the study findings:

1. A blueprint for future outbreak predictions

The completed evolutionary map of the SARS-coronavirus provides a blueprint for the prediction of the future sequence of events should SARS re-emerges. This foresight would allow for the better planning of public health control measures to prevent the occurrence of major outbreaks.

2. Encouraging news for vaccine development

The mutation rate of the SARS-coronavirus is shown to be moderate in comparison with those rapidly-mutating viruses, such as the virus for AIDS. This suggests that there is a greater likelihood that if vaccines are successfully developed to prevent SARS infection, then they are more likely to remain effective than vaccines for the more rapidly mutating viruses.

3. Implication for the development of diagnostic tests

For diagnostic tests to be effective for the detection of the different strains of the SARS-coronaviruses, the tests should be developed to target regions of the virus genome that are less likely to mutate.

　　In conclusion, this study pieces together the different chapters of the complete evolutionary story of the SARS-coronavirus and represents a significant milestone in the understanding of SARS.