title: Impact and regulation of lambda interferon response in human metapneumovirus infection.
abstract: Human metapneumovirus (hMPV) is a respiratory paramyxovirus that is distributed worldwide and induces significant airway morbidity. Despite the relevance of hMPV as a pathogen, many aspects of the immune response to this virus are still largely unknown. In this report, we focus on the antiviral immune response, which is critical for viral clearance and disease resolution. Using in vitro and in vivo systems, we show that hMPV is able to induce expression of lambda interferon 1 (IFN-λ1), IFN-λ2, IFN-λ3, and IFN-λ4. The induction of IFN-λ expression by hMPV was dependent on interferon regulatory factor 7 (IRF-7) expression but not on IRF-3 expression. Treatment of hMPV-infected mice with IFN-λ reduced the disease severity, lung viral titer, and inflammatory response in the lung. Moreover, the IFN-λ response induced by the virus was regulated by the expression of the hMPV G protein. These results show that type III interferons (IFN-λs) play a critical protective role in hMPV infection.
  
  
  OBJECTIVE
  Human metapneumovirus (hMPV) is a pathogen of worldwide importance. Despite the relevance of hMPV as a pathogen, critical aspects of the immune response induced by this virus remain unidentified. Interferons (IFNs), including IFN-λ, the newest addition to the interferon family, constitute an indispensable part of the innate immune response. Here, we demonstrated that IFN-λ exhibited a protective role in hMPV infection in vitro and in an experimental mouse model of infection.
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Ma Del Rocío
authors.initials: Mdel R
authors.lastname: Baños-Lara
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Harvey
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mendoza
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Simms
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Chouljenko
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Wakamatsu
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: K Gus
authors.initials: KG
authors.lastname: Kousoulas
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA Center for Experimental Infectious Disease Research, Louisiana State University, Baton Rouge, Louisiana, USA aguerrp@lsu.edu.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Guerrero-Plata
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000096:biosynthesis*; D008168:Lung / Q000473:pathology / Q000821:virology; D029121:Metapneumovirus / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018184:Paramyxoviridae Infections / Q000276:immunology*; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D050839:Interferon Regulatory Factor-7; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human