Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies

Stark, Caren J; Atreya, CD

A study on the evolving S protein molecular diversity in SARS-CoV isolates and its unexpected profound immunofunctional effects illustrates this point [68] . The S protein exhibited minor genetic diversity among 8 strains transmitted during human outbreaks in early 2003. Synthetic versions of these S variants with human preferred codons were tested for 1) their ability to bind the receptor (hACE-2), and 2) their sensitivity to antibody neutralization with viral pseudotypes. In these sets of experiments, substantial functional differences were found in S derived from a Guangdong province case -isolate and two palm civets isolates. Antibodies that neutralized most human isolatesderived S proteins unexpectedly enhanced entry mediated by the civet virus-derived S proteins [68] . This novel observation emphasizes the need to understand the molecular potential of the SARS-CoV genome in developing vaccines to prevent human disease. As mentioned previously, studies also point to the fact that variability in the S protein from early to late disease outbreak stages has been detected [18] . There is a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing genome of SARS-CoV indicates the potential variability of such interactions [25] . Development of successful vaccines against SARS virus therefore depends on the progress we make in these areas in the immediate future.