title: Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques.
abstract: Innate immune responses have a critical role in the control of early virus replication and dissemination. It remains unknown, however, how severe acute respiratory syndrome coronavirus (SARS-CoV) evades respiratory innate immunity to establish a systemic infection. Here we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387(+), and CD163(+) monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells and migrated into the tonsils and/or draining lymph nodes within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages, and the DC network in mucosal tissues and highlights the fact that, while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically.
authors.affiliation: AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, P.R. China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.affiliation: AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: K
authors.initials: K
authors.lastname: Nishiura
authors.affiliation: AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.affiliation: AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: C
authors.initials: C
authors.lastname: Midkiff
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: X
authors.initials: X
authors.lastname: Alvarez
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, P.R. China.
authors.forename: C
authors.initials: C
authors.lastname: Qin
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lackner
authors.affiliation: AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D017934:Coronavirus / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008253:Macaca mulatta / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D012367:RNA, Viral / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D012367:RNA, Viral