Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae
Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae
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DOI：
10.1086/368163
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发表时间：
2003-03-15
影响因子：
6.4
通讯作者：
Bartmess, KC
中科院分区：
文献类型：
--
作者：
McCullers, JA;Bartmess, KC
流感病毒和肺炎链球菌之间存在致命的协同作用，导致流感流行期间死亡率过高。使用病毒-细菌协同作用的模型，我们评估了流感病毒神经氨酸酶（NA）在引发小鼠肺炎球菌感染中的作用。选择性NA抑制剂奥司他韦的管理改善生存，独立于病毒复制和流感的发病率。肺部病理检查和肺部病变的实时成像，使用生物发光肺炎球菌，表明NA抑制的效果是限制早期感染期间肺炎球菌肺炎的程度。感染小鼠肺中唾液酸的粘附试验和免疫组织化学染色表明，流感病毒NA通过从肺中剥离唾液酸，从而暴露肺炎球菌粘附的受体，从而增强肺炎的发展。选择性NA抑制剂可能是有用的临床中断这种新的协同作用机制，并防止继发性细菌性肺炎的过度死亡。
A lethal synergism exists between influenza virus and Streptococcus pneumoniae, accounting for excess mortality during influenza epidemics. Using a model of viral-bacterial synergism, we assessed the role that the influenza virus neuraminidase (NA) has in priming mice for pneumococcal infection. Administration of the selective NA inhibitor oseltamivir improved survival, independent of viral replication and morbidity from influenza. Both pathologic examination of the lungs and live imaging of pneumonic lesions, using a bioluminescent pneumococcus, suggested that the effect of NA inhibition was to limit the extent of pneumococcal pneumonia during early infection. Adherence assays and immunohistochemical staining for sialic acids in lungs from infected mice demonstrated that the influenza virus NA potentiates development of pneumonia by stripping sialic acid from the lung, thus exposing receptors for pneumococcal adherence. Selective NA inhibitors may be useful clinically to interrupt this novel mechanism of synergism and to prevent excess mortality from secondary bacterial pneumonia.