Lung pathology of fatal severe acute respiratory syndrome

Nicholls, John M.; Poon, Leo L. M.; Lee, Kam C.; Ng, Wai Fu; Lai, Sik To; Leung, Chung Ying; Chu, Chung M.; Hui, Pui Wah; Mak, Kong Ling; Lim, Wilina; Yan, Kin W.; Chan, Kwok Hung; Tsang, Ngai Chong; Guan, Yi; Yuen, Kwok‐Yung; Peiris, J. S. Malik

doi:10.1016/s0140-6736(03)13413-7

Cited by 1,000 publications

(1,125 citation statements)

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“…Thus, the prominent accumulation of interstitial and alveolar M in the lungs of patients severely affected by SARS has raised the possibility that pulmonary M could be one of the primary targets of SARS-CoV (8). However, the rarely detected viral genome and complete absence of viral Ags or viral particles in pulmonary M , as revealed by subsequent studies, in which the cellular and tissue distribution of SARS-CoV was examined in postmortem lung tissues by in situ hybridization and immunohistochemistry, strongly suggest that they might function as scavengers rather than as the prime targets for this virus (9,43).…”

Section: Discussionmentioning

confidence: 99%

“…SARS is a highly contagious and life-threatening respiratory disease with the lower respiratory tract (e.g., the lungs) as its main target of the pathogenic process (3,8,9). Immunopathological examination of postmortem lung tissues from SARS patients revealed diffuse alveolar damage with prominent pneumocytic hyperplasia and accumulation of alveolar and interstitial macrophages (M ), as well as other pathological manifestations characteristic of acute respiratory disease syndrome resulting from massive inflammatory responses in the lungs.…”

mentioning

confidence: 99%

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Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Tseng

Perrone

Zhu

et al. 2005

The Journal of Immunology

146

149

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Severe acute respiratory syndrome (SARS) caused by a novel human coronavirus (CoV), designated SARS-CoV, is a highly contagious respiratory disease with the lungs as a major target. Although the exact mechanism of SARS-CoV pathogenesis remains unknown, an intense, ill-regulated local inflammatory response has been suggested as partially responsible for the devastating lung pathology. We investigated the interaction of SARS-CoV with human macrophages (Mφ) and dendritic cells (DC), two key innate immune cells of the host immune system, by focusing on their susceptibility to viral infection and subsequent responses (e.g., phenotypic maturation, T cell-priming activity, phagocytosis, and cytokine production). We found neither cell to be permissive for SARS-CoV replication. However, incubation of Mφ and DC with live, but not gamma irradiation-inactivated, viruses appeared to better sustain their viability. Also, exposure to infectious SARS-CoV led to the phenotypic and functional maturation of DC, with regard to MHC class II and costimulatory molecule expression, T cell-stimulatory capacity, and cytokine production, respectively. Cytokine production was also observed for Mφ, which were refractory to cell surface phenotypic changes. Strikingly, live SARS-CoV could further prime cell types to respond to a suboptimal dose of bacterial LPS (100 ng/ml), resulting in massive release of IL-6 and IL-12. However, the endocytic capacity (e.g., Ag capture) of Mφ was significantly compromised upon exposure to infectious SARS-CoV. This study is the first demonstration that although SARS-CoV does not productively infect human Mφ or DC, it appears to exert differential effects on Mφ and DC maturation and functions, which might contribute to SARS pathogenesis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome and the Innate Immune Responses: Modulation of Effector Cell Function without Productive Infection

Tseng

Perrone

Zhu

et al. 2005

The Journal of Immunology

146

149

View full text Add to dashboard Cite

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“…It has been reported that some patients experience deterioration during the second week of illness despite a decreasing viral load and it has been suggested that there may be an immunopathologic component contributing to lung damage (13)(14)(15).…”

mentioning

confidence: 99%

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

Zhou

De-sheng

et al. 2006

The Journal of Immunology

107

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Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-γ ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2+ SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411–420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-γ-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.

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“…Sin embargo, su uso en diversas series se ha asociado a un mejor pronóstico, especialmente cuando han sido utilizados entre los días 6 a 8 de la enfermedad. Nichols et al 35 realizaron estudios postmortem en seis pacientes que fallecieron debido al SARS, y encontraron proliferación hiperplásica epitelial asociada con hemofagocitosis. La presencia de este fenómeno se ha asociado clínicamente a una regulación alterada de la cascada inflamatoria de las citocinas, lo cual podría considerarse como un marcador que sugiere cómo la utilización clínica de esteroides podría ser de gran importancia.…”

Section: Tratamientounclassified

“…La presencia de este fenómeno se ha asociado clínicamente a una regulación alterada de la cascada inflamatoria de las citocinas, lo cual podría considerarse como un marcador que sugiere cómo la utilización clínica de esteroides podría ser de gran importancia. 35 * Hong Kong, República Popular de China, Taiwán.…”

Section: Tratamientounclassified