Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation
Differential Cell Line Susceptibility to the Emerging Novel Human Betacoronavirus 2c EMC/2012: Implications for Disease Pathogenesis and Clinical Manifestation
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DOI：
10.1093/infdis/jit123
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发表时间：
2013-06-01
影响因子：
6.4
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
--
作者：
Chan, Jasper Fuk-Woo;Chan, Kwok-Hung;Yuen, Kwok-Yung
新出现的新型人类β冠状病毒2c EMC/2012（HCoV - EMC）近期从患有重症肺炎和肾衰竭的患者体内分离出来，且与56%这一不明原因的高粗死亡率相关。我们对28种细胞系进行了细胞系敏感性研究。发现HCoV - EMC可感染人类呼吸道（极化气道上皮细胞系Calu - 3、胚胎成纤维细胞系HFL和肺腺癌细胞系A549）、肾脏（胚胎肾细胞系HEK）、肠道（结直肠腺癌细胞系Caco - 2）、肝细胞（肝细胞癌细胞系Huh - 7）以及组织细胞（恶性组织细胞瘤细胞系His - 1），这可通过在培养上清液中检测到高病毒载量或病毒载量增加、通过免疫染色检测到病毒核蛋白表达和/或检测到细胞病变效应来证明。尽管被感染的人类神经元细胞系（NT2）以及被感染的单核细胞和T淋巴细胞细胞系（THP - 1、U937和H9）病毒载量有所增加，但它们相对较低的病毒产量与核蛋白表达缺失和细胞病变效应相符。这种人类组织嗜性范围比所有其他人类冠状病毒更广，包括SARS冠状病毒、HCoV - OC43、HCoV - HKU1、HCoV - 229E和HCoV - NL63，这或许可以解释与该疾病相关的高死亡率。近期一项细胞系敏感性研究表明，HCoV - EMC能够感染灵长类、猪和蝙蝠的细胞，因此可能跨越物种屏障。我们发现HCoV - EMC还能够感染果子狸肺成纤维细胞和兔肾细胞系。这些发现对HCoV - EMC的诊断、发病机制和传播具有重要意义。
The emerging novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) was recently isolated from patients with severe pneumonia and renal failure and was associated with an unexplained high crude fatality rate of 56%. We performed a cell line susceptibility study with 28 cell lines. HCoV-EMC was found to infect the human respiratory tract (polarized airway epithelium cell line Calu-3, embryonic fibroblast cell line HFL, and lung adenocarcinoma cell line A549), kidney (embryonic kidney cell line HEK), intestinal tract (colorectal adenocarcinoma cell line Caco-2), liver cells (hepatocellular carcinoma cell line Huh-7), and histiocytes (malignant histiocytoma cell line His-1), as evident by detection of high or increasing viral load in culture supernatants, detection of viral nucleoprotein expression by immunostaining, and/or detection of cytopathic effects. Although an infected human neuronal cell line (NT2) and infected monocyte and T lymphocyte cell lines (THP-1, U937, and H9) had increased viral loads, their relatively lower viral production corroborated with absent nucleoprotein expression and cytopathic effects. This range of human tissue tropism is broader than that for all other HCoVs, including SARS coronavirus, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, which may explain the high mortality associated with this disease. A recent cell line susceptibility study showed that HCoV-EMC can infect primate, porcine, and bat cells and therefore may jump interspecies barriers. We found that HCoV-EMC can also infect civet lung fibroblast and rabbit kidney cell lines. These findings have important implications for the diagnosis, pathogenesis, and transmission of HCoV-EMC.