Division of Influenza/Respiratory Viruses, Robert Koch Institut, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Infect Dis. 2012 Dec 1;206(11):1685-94. doi: 10.1093/infdis/jis455. Epub 2012 Jul 24.
Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied.
We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures.
Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses.
These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.
高致病性禽流感 H5N1 病毒在人类肺部中优先感染肺泡 II 型上皮细胞。然而，由于尚未系统研究其他流感病毒的主要靶细胞，因此尚不清楚这种细胞嗜性是否有助于高病毒毒力。
我们首次比较了人源高致病性禽流感 A 型 H5N1 亚型和其他动物流感 A 病毒在原代人肺器官培养物中的复制、嗜性和细胞因子诱导。
亚型 H5N1 和人源适应的 H1N1 和 H3N2 病毒在肺部组织中高效复制，而经典猪流感和低致病性禽流感病毒的繁殖能力较差。然而，所有检测到的病毒几乎都仅在 II 型肺泡上皮细胞中检测到，而肺泡巨噬细胞的参与较少。感染低致病性和高致病性禽流感病毒会引起细胞因子和趋化因子的强烈诱导，而感染人源和大流行 H1N1-2009 病毒只会引起微弱的反应。
这些发现表明，流感 A 病毒在人类肺部中的致病性差异不能归因于明显的细胞嗜性。相反，高或低病毒致病性与病毒在 II 型肺泡上皮细胞中有效复制和应对诱导的细胞因子反应的特定菌株能力有关。
