Expression Of Feline Angiotension Converting Enzyme 2, Mutant Construction And Its Analysis As SARS-CoV Receptor

A world-wide epidemic, sever acute respiratory syndrome caused more than 8000 infections with a fatality rate of about 10% in 2002 winter and 2003. SARS coronavirus was its etiological agent. Animals play an important role in the SARS-CoV spread. In 2003, three strains of SARS-CoV, whose genome sequences share 99% similarities with those of human isolates, were isolated from civet cats. Bats were recently reported to carry SARS-related virus termed SARS-like coronavirus (SL-CoV) .The genome sequences of these viruses share 92% similarities with that of human SARS-CoV. It seems that these SARS-like coronavirus do not directly infect human. The bats may be a natural resrvoir of SARS-CoV. The previously suspected host-civet cat perhaps just a intermediate host or carrier transmitting the wild virus to human. Domestic cats can be infected with SARS-CoV. During SARS outbreak in 2003, SARS-CoV in domestic cats was detected in patients' pet cats in Hongkong. The experimental infection further demonstrated that domestic cats were susceptible to SARS-CoV infection.Human angiotensin-converting enzyme 2 (hACE2) was a functional receptor for SARS-CoV. This lab firstly cloned the feline ACE2 (fACE2) gene from domestic cats. It was found that feline ACE2 gene possesses a high similarity with human ACE2 at both nucleotide and amino acid levels. In this study was aimed to investigate further the feline ACE2 as the potential SARS-CoV receptor. The results were summarized as follows:(1) The three-dimension structure prediction for feline ACE2: The amino acid sequences encoded by felineACE2 gene share 85% similarities with that of human ACE2. Since the X-ray crystal structure of human ACE2 is published, we used human ACE2 structure as the template to predict the three-dimension structure of feline ACE2 by homologous modeling. The feline ACE2 dimensional structure is very similar to that of human ACE2. Furthermore, the deduced amino acids between cat and human ACE2 that contact with SARS-CoV receptor binding domain (RBD) shared a high homology (15/18).