Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS
Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS
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DOI：
10.1371/journal.pmed.0030027
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发表时间：
2006-02-01
期刊：
影响因子：
15.8
通讯作者：
Wong, M
中科院分区：
文献类型：
--
作者：
Nicholls, JM;Butany, J;Wong, M
研究背景严重急性呼吸综合征冠状病毒（SARS-CoV）在SARS患者肺部的细胞定位对于证实病毒与疾病的病因学联系以及理解疾病的发病机制具有重要意义。据我们所知，还没有全面的研究调查病毒感染在细胞水平在human.Methods和结果，我们收集了最大的一系列SARS死亡病例的尸检材料，迄今为止，合并的病理材料从两个地区参与2003年全球SARS疫情在中国香港，和多伦多，加拿大。我们研制了一种抗SARS冠状病毒核蛋白的单克隆抗体，并将其与原位杂交（ISH）结合，对来自香港和多伦多的32例SARS患者的尸检肺组织进行了分析。我们将这些检测结果与每例患者的肺部病理和临床病程进行了比较。SARS-CoV核蛋白和RNA分别通过免疫组织化学和ISH检测，主要在肺泡肺细胞中，较少在巨噬细胞中。在发病后两周内死亡的7例患者中有4例检测到这种定位，而在症状发作后两周内死亡的25例患者中没有检测到这种定位。结论肺泡上皮细胞是SARS-CoV的主要靶细胞，随后巨噬细胞感染。病毒复制似乎仅限于症状发作后的前两周，在此期间后几乎没有继续广泛复制的证据。如果将来考虑抗病毒治疗，则应重点关注这两周的急性临床疾病。
Background Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.Methods and Findings We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.Conclusions The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.