Severe acute respiratory syndrome (SARS) is an emerging infectious disease 
associated with a new coronavirus, SARS-CoV. Pulmonary involvement is the 
dominant clinical feature but extra-pulmonary manifestations are also common. 
Factors that account for the wide spectrum of organ system involvement and 
disease severity are poorly understood and the pathogenesis of SARS-CoV 
infection remains unclear. Angiotensin converting enzyme 2 (ACE2) has recently 
been identified as the functional cellular receptor for SARS-CoV. Studies of the 
tissue and cellular distribution of SARS-CoV, and ACE2 protein expression, 
reveal new insights into the pathogenesis of this deadly disease. ACE2 is 
expressed at high level in the primary target cells of SARS-CoV, namely 
pneumocytes and surface enterocytes of the small intestine. Despite the fact 
that SARS-CoV can infect the lung and intestine, the tissue responses in these 
two organs are different. All other tissues and cell types expressing ACE2 may 
be potential targets of SARS-CoV infection. Remarkably, endothelial cells, which 
express ACE2 to a high level, have not been shown to be infected by SARS-CoV. 
There is also evidence that cell types without detectable ACE2 expression may 
also be infected by the virus. Furthermore, studies in a new human cell culture 
model have indicated that the presence of ACE2 alone is not sufficient for 
maintaining viral infection. Therefore, other virus receptors or co-receptors 
may be required in different tissues. Moreover, the interaction between SARS-CoV 
and the immunological or lymphoid system remains to be defined. It is clear that 
we are only at the dawn of our understanding of the pathogenesis of SARS. As our 
knowledge of the pathogenic mechanisms improves, a more rational approach to 
therapeutic and vaccine development can be designed in order to combat this new 
and fatal human disease.