title: Mitochondrial antiviral-signalling protein plays an essential role in host immunity against human metapneumovirus.
abstract: Human metapneumovirus (hMPV) is a common cause of respiratory tract infection in the paediatrics population. Recently, we and others have shown that retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs) are essential for hMPV-induced cellular antiviral signalling. However, the contribution of those receptors to host immunity against pulmonary hMPV infection is largely unexplored. In this study, mice deficient in mitochondrial antiviral-signalling protein (MAVS), an adaptor of RLRs, were used to investigate the role(s) of these receptors in pulmonary immune responses to hMPV infection. MAVS deletion significantly impaired the induction of antiviral and pro-inflammatory cytokines and the recruitment of immune cells to the bronchoalveolar lavage fluid by hMPV. Compared with WT mice, mice lacking MAVS demonstrated decreased abilities to activate pulmonary dendritic cells (DCs) and abnormal primary T-cell responses to hMPV infection. In addition, mice deficient in MAVS had a higher peak of viral load at day 5 post-infection (p.i.) than WT mice, but were able to clear hMPV by day 7 p.i. similarly to WT mice. Taken together, our data indicate a role of MAVS-mediated pathways in the pulmonary immune responses to hMPV infection and the early control of hMPV replication.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.|Department of Hepatobiliary Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, PR China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pediatrics, TongJi Hospital, Huazhong University of Science and Technology, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.|Department of Otorhinolaryngology, Sixth Affiliated Hospital, Sun Yat-Sen University, PR China.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Junping
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Go
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Teodora
authors.initials: T
authors.lastname: Ivanciuc
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Kolli
authors.initials: K
authors.lastname: Deepthi
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D029121:Metapneumovirus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018184:Paramyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C512612:MAVS protein, mouse