Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan

Shieh, Wun Ju; Hsiao, Chêng; Paddock, Christopher D.; Guarner, Jeannette; Goldsmith, Cynthia S.; Tatti, Kathleen M.; Packard, Michelle M.; Mueller, Laurie; Wu, Mu Zong; Rollin, Pierre E.; Su, Ih Jen; Zaki, Sherif R.

doi:10.1016/j.humpath.2004.11.006

Cited by 132 publications

(136 citation statements)

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“…4,7,11,27,33 First, the localization of the lesions in cats and ferrets is similar to that in humans: in all three species, the lesions affect mainly the alveoli and bronchioles. A clear difference is SARS-CoVassociated tracheo-bronchoadenitis, which we observed in cats, but which has not been reported in humans.…”

Section: Discussionmentioning

confidence: 91%

“…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.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

et al. 2008

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“…6). Both PRCV and SARS-CoV seem to target predominantly type 2 pneumocytes in the lungs [50,51]. Conflicting reports on the ability of SARS-CoV to infect macrophages have been discussed in the above mentioned review article [47].…”

Section: Discussionmentioning

confidence: 99%

Lung Cell Tropism and Inflammatory Cytokine-Profile of Porcine Respiratory Coronavirus Infection

Atanasova¹,

Gucht²,

Barbé³

et al. 2008

TOVSJ

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Knowledge about porcine respiratory coronavirus (PRCV) tropism was limited to morphological identification of target cells and controversial reports on replication in macrophages. This study aimed to clarify the lung cell tropism of a Belgian PRCV strain and to examine the lung profile of inflammatory cytokines for 15 days after intratracheal PRCV inoculation of gnotobiotic piglets. Until 5 days after inoculation, more than 50% of the PRCV-positive cells were type 2 pneumocytes, 30% bronchiolar epithelial cells, and 10% macrophages, as demonstrated by immunofluorescence stainings with specific cell markers. In vitro, PRCV productively infected primary porcine lung epithelial cells, but not porcine alveolar macrophages. Bronchoalveolar lavage fluids of PRCV-inoculated pigs contained high levels of interferons (IFN-, IFN-) and interleukin-6, moderate interleukin-12 and low tumour necrosis factor-levels. Our results indicate that PRCV infects primarily type 2 pneumocytes and induces lower lung cytokine levels, compared to swine influenza virus or lipopolysaccharide-complicated PRCV infections.

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“…Human SARS CoV-infected lungs show diffuse alveolar damage characterized by desquamation of epithelial cells, fibrin and collagen deposits in the alveolar space, hyperplasia of type II pneumocytes, increased mononuclear infiltrates in the interstitium, and in some cases the presence of multinucleated syncytial cells (9,13). Detection of viral nucleic acids and antigens in human tissues varies with the duration of illness (3,20). SARS CoV antigen and nucleic acid were not detected in patients with prolonged illness; however, in the small number of patients studied who had a short (1-week) duration of illness, virus was detected in pneumocytes, occasionally in macrophages, in intraalveolar necrotic debris within the alveolar septal walls, and rarely in bronchoepithelial cells.…”

Section: Vol 79 2005 Sars Coronavirus Replication In Hamsters 509mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

Roberts

Vogel

Guarner

et al. 2005

J Virol

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278

306

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Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication.

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Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan

Cited by 132 publications

References 14 publications

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

Pathology of Experimental SARS Coronavirus Infection in Cats and Ferrets

Lung Cell Tropism and Inflammatory Cytokine-Profile of Porcine Respiratory Coronavirus Infection

Severe Acute Respiratory Syndrome Coronavirus Infection of Golden Syrian Hamsters

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