Hantavirus Pulmonary Syndrome: Pathogenesis of an Emerging Infectious Disease
Hantavirus Pulmonary Syndrome: Pathogenesis of an Emerging Infectious Disease
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发表时间：
1995-03
影响因子：
6
通讯作者：
S. Zaki;P. Greer;L. Coffield;C. Goldsmith;K. B. Nolte;K. Foucar;R. Feddersen;R. Zumwalt;G. Miller;Ali S Khan;P. Rollin;T. Ksiazek;S. Nichol;B. Mahy;C. Peters
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文献类型：
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作者：
S. Zaki;P. Greer;L. Coffield;C. Goldsmith;K. B. Nolte;K. Foucar;R. Feddersen;R. Zumwalt;G. Miller;Ali S Khan;P. Rollin;T. Ksiazek;S. Nichol;B. Mahy;C. Peters
最近在美国西南部爆发的严重肺部疾病在病因学上与以前未被认识的汉坦病毒有关。该病毒已从其主要宿主——鹿鼠（Peromyscus maniculatus）中分离出来，最近命名为Sin Nombre病毒。在临床上，这种疾病被称为汉坦病毒肺综合征（HPS）。自1993年5月以来，通过临床病理检查和免疫组织化学（IHC）检测273例死于不明原因的非心源性肺水肿的患者的组织，确定了44例HPS死亡病例。在158例有合适标本的病例中，还对提取的RNA进行了血清学检测和/或逆转录聚合酶链反应（RT-PCR）扩增。当进行多次检测时，几乎所有HPS和非HPS患者的免疫组化、血清学和PCR结果都是一致的。HPS的前驱疾病与许多其他病毒性疾病相似。一致的血液学特征包括血小板减少、血液浓缩、嗜中性白细胞左移和反应性淋巴细胞。大多数致死性HPS病例的肺组织病理学特征相似（40/44），包括间质性肺炎伴可变单核细胞浸润、水肿和局灶性透明膜。然而，在四个病例中，肺部特征明显不同，包括弥漫性肺泡损伤和不同程度的严重空气空间紊乱。免疫组化分析显示，汉坦病毒抗原广泛存在于微血管内皮细胞中，特别是在肺中。在滤泡树突状细胞、巨噬细胞和淋巴细胞中也观察到汉坦病毒抗原。薄层电镜观察到肺内皮细胞中存在汉坦病毒包涵体，免疫金标法证实其身份。肺内皮细胞和巨噬细胞可见病毒样颗粒。HPS是一种新发现的，通常是致命的疾病，具有光谱的微观形态改变，这可能是严重和致命的疾病，表现为成人呼吸窘迫综合征的重要原因。
A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization. IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thinsection electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, often fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.