title: Middle East respiratory syndrome coronavirus infection: virus-host cell interactions and implications on pathogenesis.
abstract: Middle-East Respiratory Syndrome coronavirus (MERS-CoV) was identified to cause severe respiratory infection in humans since 2012. The continuing MERS epidemic with a case-fatality of more than 30% poses a major threat to public health worldwide. Currently, the pathogenesis of human MERS-CoV infection remains poorly understood. We reviewed experimental findings from human primary cells and ex vivo human lung tissues, as well as those from animal studies, so as to understand the pathogenesis and high case-fatality of MERS. Human respiratory epithelial cells are highly susceptible to MERS-CoV and can support productive viral replication. However, the induction of antiviral cytokines and proinflammatory cytokines/chemokines are substantially dampened in the infected epithelial cells, due to the antagonistic mechanisms evolved by the virus. MERS-CoV can readily infect and robustly replicate in human macrophages and dendritic cells, triggering the aberrant production of proinflammatory cytokines/chemokines. MERS-CoV can also effectively infect human primary T cells and induce massive apoptosis in these cells. Although data from clinical, in vitro and ex vivo studies suggested the potential for virus dissemination, extrapulmonary involvement in MERS patients has not been ascertained due to the lack of autopsy study. In MERS-CoV permissive animal models, although viral RNA can be detected from multiple organs of the affected animals, the brain of human DPP4-transgenic mouse was the only extrapulmonary organ from which the infectious virus can be recovered. More research findings on the pathogenesis of MERS and the tissue tropisms of MERS-CoV may help to improve the treatment and infection control of MERS.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China. jiezhou@hku.hk.|Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Special Administrative Region, China. jiezhou@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China. jiezhou@hku.hk.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China. hinchu@hku.hk.|Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Special Administrative Region, China. hinchu@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China. hinchu@hku.hk.
authors.forename: Hin
authors.initials: H
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China. jfwchan@hku.hk.|Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Special Administrative Region, China. jfwchan@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China. jfwchan@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, China. jfwchan@hku.hk.
authors.forename: Jasper Fuk-Woo
authors.initials: JF
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, China. kyyuen@hku.hk.|Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Special Administrative Region, China. kyyuen@hku.hk.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, China. kyyuen@hku.hk.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, China. kyyuen@hku.hk.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000818:Animals; D017209:Apoptosis; D018352:Coronavirus Infections / Q000473:pathology* / Q000821:virology*; D003713:Dendritic Cells / Q000821:virology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008168:Lung / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000821:virology; D065207:Middle East Respiratory Syndrome Coronavirus / Q000472:pathogenicity* / Q000502:physiology*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication