title: Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation.
abstract: 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.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong Special Administrative Region, China.
authors.forename: Jasper Fuk-Woo
authors.initials: JF
authors.lastname: Chan
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.forename: Garnet Kwan-Yue
authors.initials: GK
authors.lastname: Choi
authors.forename: Kelvin Kai-Wang
authors.initials: KK
authors.lastname: To
authors.forename: Herman
authors.initials: H
authors.lastname: Tse
authors.forename: Jian-Piao
authors.initials: JP
authors.lastname: Cai
authors.forename: Man Lung
authors.initials: ML
authors.lastname: Yeung
authors.forename: Vincent Chi-Chung
authors.initials: VC
authors.lastname: Cheng
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Che
authors.forename: Susanna Kar-Pui
authors.initials: SK
authors.lastname: Lau
authors.forename: Patrick Chiu-Yat
authors.initials: PC
authors.lastname: Woo
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D002460:Cell Line; D017934:Coronavirus / Q000472:pathogenicity* / Q000502:physiology; D018352:Coronavirus Infections / Q000473:pathology* / Q000821:virology*; D006801:Humans; D019562:Viral Load; D056189:Viral Tropism; D014776:Virus Cultivation; D014779:Virus Replication