Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

Ding, Yan‐Qing; He, Li; Zhang, Qingling; Huang, Zhongxi; Che, Xin; Hou, Jin-lin; Wang, Huijun; Shen, Hong; Qiu, Li-wen; Li, Zhuguo; Geng, Jian Guo; Cai, Junjie; Han, Hui-xia; Li, Xin; Kang, Wei; Weng, Desheng; Liang, Ping; Jiang, Shibo

doi:10.1002/path.1560

Cited by 1,013 publications

(1,046 citation statements)

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“…5). The principal targets for SARS-CoV infection in humans are the lung and gastrointestinal tract (25,26). SARS-CoV or viral antigens have been detected in type II alveolar cells in lung, and in liver, kidney, sweat glands, parathyroid, brain, pancreas, and adrenal glands (26).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, RT-PCR and immunocytochemistry showed that ACE2 mRNA and protein are expressed on oral, nasal, and intestinal mucosa, alveolar epithelial cells in lung, stomach, skin, lymph nodes, thymus, bone marrow, spleen liver, kidney, and brain, and arterial and venous endothelial cells and arterial smooth muscle cells in many organs (38)(39)(40)(41). These sites for ACE2 expression include most of the sites for SARS-CoV replication in autopsy specimens (26). Our data show that human CD209L can also mediate infection by SARS-CoV, although it is a much less efficient receptor than human ACE2.…”

Section: Discussionmentioning

confidence: 99%

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CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Jeffers

Tusell

Gillim-Ross

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

583

570

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Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus called SARS-CoV (1-3). The virus causes atypical pneumonia with diffuse alveolar damage with an overall mortality of Ϸ10% that ranges from 0% in children and 50% in persons over 65 (2). Coronaviruses bind to their glycoprotein receptors by the Ϸ200-kDa spike glycoprotein, S, on the viral envelope. Identification of virus receptors can provide insight into mechanisms of virus entry, tissue tropism, pathogenesis, and host range.Several types of receptors were previously identified for coronavirus S glycoproteins. The receptors for the murine coronavirus mouse hepatitis virus are murine carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) and related murine glycoproteins in the carcinoembryonic antigen family in the Ig superfamily (4). The receptors for human coronavirus 229E (HCoV-229E), transmissible gastroenteritis virus of swine, and feline coronavirus in genetic group 1 are aminopeptidase N (APN) glycoproteins (5-8).Angiotensin-converting enzyme 2 (ACE2) was found to be an efficient receptor for the S glycoprotein of SARS-CoV (9, 10). Because the Vero line of rhesus monkey kidney cells is highly susceptible to infection with SARS-CoV, Li et al. (9) used a codon-optimized soluble SARS-CoV spike glycoprotein (amino acids 12-672) fused to the Fc domain of human IgG1 to immunoprecipitate a putative receptor glycoprotein from Vero cell membranes and identified the simian ACE2 protein by mass spectrometry. They showed that expression of recombinant human ACE2 greatly enhanced the susceptibility of human 293T cells to infection by SARS-CoV. Wang et al. (10) independently demonstrated that human ACE2 is a receptor for SARS-CoV by transducing HeLa cells with a retrovirus library of cDNAs from Vero E6 cells and by using flow cytometry to select transduced cells that bound to purified soluble SARS-CoV S glycoprotein (amino acids 14-502) with a 6-histidine tag. They found that the simian cDNA in these cells, which encoded triosephosphate isomerase, enhanced expression of human ACE2 by inserting into the HeLa cell genome immediately upstream of the ACE2 ORF. Murine NIH 3T3 cells expressing recombinant human ACE2, but not those expressing recombinant triosephosphate isomerase, were susceptible to infection by HIV pseudovirus expressing SARS-CoV S protein.In this report, we describe the discovery of an additional receptor for SARS-CoV, CD209L (also called L-SIGN, DC-SIGNR, and DC-SIGN2) (11). Our strategy for identifying a SARS-CoV receptor was to transduce a human lung cDNA library carried by a retroviral vector into Chinese hamster ovary (CHO) cells and use flow cytometry to select transduced CHO cells that bound soluble, codon-optimized, c-myc-tagged SARSCoV S 590 glycoprotein (amino acids 1-590) expressed in 293T cells. The SARS-CoV S 590 -binding cells were then challenged with infectious SARS-CoV, and infection was demonstrated by detection of subgenomic viral RNA synthesis and immunofluorescence with antiviral antibody. The finding that ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Jeffers

Tusell

Gillim-Ross

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

583

570

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“…4,7,12,25,27 This lesion corresponds in part to the cell types in the respiratory tract in which SARS-CoV antigen has been detected: alveolar epithelial cells (primarily type II pneumocytes), bronchial epithelial cells, and alveolar macrophages. 3,29,33,38,40 Cases of longer duration (more than 10 days) demonstrated features of organizing-phase or late-stage DAD. 7,27 Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor for the attachment to and uptake of SARS-CoV in host cells.…”

mentioning

confidence: 99%

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

et al. 2008

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Abstract. The pathology of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV, in the respiratory tracts of these species is unknown. We observed SARS-CoV antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ACE2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. All infected cats and ferrets had diffuse alveolar damage associated with SARS-CoV antigen expression. A novel SARS-CoVassociated lesion was tracheo-bronchoadenitis in cats. SARS-CoV antigen expression occurred mainly in type I and II pneumocytes and serous cells of tracheo-bronchial submucosal glands of cats and in type II pneumocytes of ferrets. ACE2 expression occurred mainly in type I and II pneumocytes, tracheo-bronchial goblet cells, serous epithelial cells of tracheo-bronchial submucosal glands in cats, and type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets. In conclusion, the pathology of SARS-CoV infection in cats and ferrets resembles that in humans except that syncytia and hyaline membranes were not observed. The identification of tracheo-bronchoadenitis in cats has potential implications for SARS pathogenesis and SARS-CoV excretion. Finally, these results show the importance of ACE2 expression for SARS-CoV infection in vivo: whereas ACE2 expression in type I and II pneumocytes in cats corresponded to SARS-CoV antigen expression in both cell types, expression of both ACE2 and SARS-CoV antigen in ferrets was limited mainly to type II pneumocytes.

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“…The targets included the lymphocytes, the epithelium of the distal tubules of the kidney, and the submucosal lymphoid complex of the gut, the spleen, and the lymph nodes [7,8]. However, only sporadic information is available regarding the involvement of reproductive organs in SARS patients [9,10]. Because it is known that viruses such as HIV, HBV, and mumps can enter the testis and cause viral orchitis and, in some instances, result in male infertility and testicular tumor [11], we investigated the possible damage of the testis in SARS patients and the effects of SARS on spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Orchitis: A Complication of Severe Acute Respiratory Syndrome (SARS)1

Lei

Chi

et al. 2006

Biology of Reproduction

387

455

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Severe acute respiratory syndrome (SARS) coronavirus has been known to damage multiple organs; however, little is known about its impact on the reproductive system. In the present study, we analyzed the pathological changes of testes from six patients who died of SARS. Results suggested that SARS caused orchitis. All SARS testes displayed widespread germ cell destruction, few or no spermatozoon in the seminiferous tubule, thickened basement membrane, and leukocyte infiltration. The numbers of CD3þ T lymphocytes and CD68þ macrophages increased significantly in the interstitial tissue compared with the control group (P , 0.05). SARS viral genomic sequences were not detected in the testes by in situ hybridization. Immunohistochemistry demonstrated abundant IgG precipitation in the seminiferous epithelium of SARS testes, indicating possible immune response as the cause for the damage. Our findings indicated that orchitis is a complication of SARS. It further suggests that the reproductive functions should be followed and evaluated in recovered male SARS patients.immunohistochemistry, in situ hybridization, orchitis, SARS, spermatogenesis, testis

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Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

Cited by 1,013 publications

References 25 publications

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

Orchitis: A Complication of Severe Acute Respiratory Syndrome (SARS)1

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