A novel subset of putative stem/progenitor CD34(+)Oct-4(+) cells is the major target for SARS coronavirus in human lung

Chen, Yongxiong; Chan, Vera Sau-Fong; Zheng, Bojian; Chan, Kelvin Yuen-Kwong; Xu, Xiaoning; To, Leo Yuk-Fai; Huang, Fang-Ping; Khoo, Ui-Soon; Lin, Chen-Lung Steve

SARS is an acute respiratory disease from infection of a novel coronavirus (SARS-CoV) that spreads mainly through the respiratory route ( 1 -3 ) , with angiotensin-converting enzyme 2 (ACE2) as the only known functional receptor ( 4 ) . One of the clinical features in SARS infection is continuous deterioration of lung function and the obvious loss of lung repair capacity after viral load has declined ( 5 ) . However, the pathogenesis for SARS-CoV infection, for which characterizing the nature of virus-infected cells is crucial, is still ill-defi ned. Reports in the literature regarding the identity of SARS Ï© cells are unconvincing either because no colocalization study was performed or because of technical limitations. Results in the literature are also inconsistent in that some reports suggested type I pneumocytes, whereas others suggested type II pneumocytes, as the major target in humans and in simian models ( 6 -11 ) . It has also been implied that these SARS Ï© cells express cytokeratin, whether they are described as type I or type II cells ( 6 -10, 12 ) . It is also a concern that none of these reports demonstrated colocalization of ACE2 expression with SARSinfected cells. Using multicolor colocalization techniques, we previously reported that cells containing SARS-CoV antigen in the autopsy lung of SARS patients expressed ACE2 and liver/lymph node -specifi c ICAM-3 -grabbing non-integrin (L-SIGN; CD209L) ( 13 ) . L-SIGN is a SARS-CoV binding receptor that mediates proteasome-dependent viral degradation and is expressed in cytokeratin Ï© respiratory epithelia (Fig. S1 , available at http://www.jem.org/cgi/ content/full/jem.20070462/DC1) (13) . L-SIGN can also facilitate SARS-CoV infection/replication in trans ( 13 ) . In this study, we further characterize the SARS-infected cells and show that a novel subset of putative stem/progenitor CD34 Ï© Oct-4 Ï© cells are the only cells expressing ACE2 in the human lung and are the major target for SARS-CoV infection.