【病毒外文文獻】2007 A novel subset of putative stem_progenitor CD34+Oct-4+ cells is the major target for SARS coronavirus in human lung

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The Journal of Experimental Medicine 2529 BRIEF DEFINITIVE REPORT JEM The Rockefeller University Press 30 00 Vol 204 No 11 October 29 2007 2529 2536 www jem org cgi doi 10 1084 jem 20070462 SARS is an acute respiratory disease from infec tion 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 infec tion is continuous deterioration of lung function and the obvious loss of lung repair capacity after viral load has declined 5 However the patho genesis for SARS CoV infection for which characterizing the nature of virus infected cells is crucial is still ill de ned Reports in the lit erature regarding the identity of SARS cells are unconvincing either because no colocalization study was performed or because of technical limitations Results in the literature are also in consistent 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 cells express cyto keratin 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 co localization of ACE2 expression with SARS infected 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 speci 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 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 repli cation in trans 13 In this study we further characterize the SARS infected cells and show that a novel subset of putative stem progenitor CD34 Oct 4 cells are the only cells express ing ACE2 in the human lung and are the major target for SARS CoV infection RESULTS AND DISCUSSION SARS cells in alveoli and terminal bronchioles do not express cytokeratin or surfactant To characterize the phenotype of SARS cells autopsy lung samples from nine SARS patients CORRESPONDENCE Chen Lung Steve Lin steve lin imperial ac uk Y Chen and V S F Chan contributed equally to this work The online version of this article contains supplemental material A novel subset of putative stem progenitor CD34 Oct 4 cells is the major target for SARS coronavirus in human lung Yongxiong Chen 1 4 Vera Sau Fong Chan 1 4 Bojian Zheng 2 Kelvin Y uen Kwong Chan 3 Xiaoning Xu 6 Leo Yuk Fai To 1 4 Fang Ping Huang 5 Ui Soon Khoo 3 and Chen Lung Steve Lin 1 4 1 Department of Surgery 2 Department of Microbiology and 3 Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China 4 Division of Surgery Oncology Reproductive Biology and Anaesthetics Faculty of Medicine and 5 Department of Molecular Genetics and Rheumatology Division of Medicine Imperial College London Hammersmith Hospital London W12 0NN UK 6 Human Immunology Unit The Weatherall Institute of Molecular Medicine University of Oxford Oxford OX3 9DS UK Identi cation of the nature of severe acute respiratory syndrome SARS infected cells is crucial toward understanding the pathogenesis Using multicolor colocalization techniques we previously reported that SARS cells in the lung of fatally infected patients expressed the only known functional receptor angiotensin converting enzyme 2 and also a binding receptor liver lymph node speci c ICAM 3 grabbing non integrin CD209L In this study we show that SARS infected cells also express the stem progenitor cell markers CD34 and Oct 4 and do not express cytokeratin or surfactant These putative lung stem progenitor cells can also be identi ed in some non SARS individuals and can be infected by SARS coronavirus ex vivo Infection of these cells may contribute to the loss of lung repair capacity that leads to respiratory failure as clinically observed on March 15 2015 jem rupress org Downloaded from Published October 8 2007 http jem rupress org content suppl 2007 10 05 jem 20070462 DC1 html Supplemental Material can be found at