title: Effect of in vitro syncytium formation on the severity of human metapneumovirus disease in a murine model.
abstract: Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infections (ARTI) in children, elderly individuals and immunocompromised patients. In vitro, different HMPV strains can induce variable cytopathic effects ranging from large multinucleated syncytia to focal cell rounding. In this study, we investigated the impact of different in vitro phenotypes of two HMPV strains on viral replication and disease severity in a BALB/c mouse model. We first generated two recombinant GFP-expressing HMPV viruses: C-85473, a syncytium-inducing strain (rC-85473) belonging to the A1 subtype and CAN98-75, a focal cell rounding-inducing strain (rCAN98-75) of the B2 subtype. We subsequently exchanged the F genes of both strains to create the chimeric viruses rC-85473_F and rCAN98-75_F. We demonstrated that the F protein was the sole protein responsible for the syncytium phenotype and that viruses carrying a syncytium-inducing F protein replicated to significantly higher titers in vitro. In vivo, however, the virulence and replicative capacity of the different HMPV strains did not appear to be solely dependent on the F gene but also on the viral background, with the strains containing the C-85473 background inducing more weight loss as well as increased lung viral titers, pro-inflammatory cytokines and inflammation than strains containing the CAN98-75 background. In conclusion, the F protein is the main determinant of syncytium formation and replication kinetics in vitro, although it is not the only factor implicated in HMPV disease severity in mice.
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Laetitia
authors: L
authors: Aerts
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Marie-Hélène
authors: MH
authors: Cavanagh
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Julia
authors: J
authors: Dubois
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Julie
authors: J
authors: Carbonneau
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Chantal
authors: C
authors: Rhéaume
authors: Anatomopathologie et cytologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec and Université Laval, Quebec City, QC, Canada.
authors: Sophie
authors: S
authors: Lavigne
authors: Anatomopathologie et cytologie, Institut Universitaire de Cardiologie et de Pneumologie de Québec and Université Laval, Quebec City, QC, Canada.
authors: Christian
authors: C
authors: Couture
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Marie-Ève
authors: MÈ
authors: Hamelin
authors: Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval, Quebec, Canada.
authors: Guy
authors: G
authors: Boivin
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005814:Genes, Viral; D015726:Giant Cells / Q000473:pathology* / Q000821:virology; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000821:virology; D029121:Metapneumovirus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D008807:Mice, Inbred BALB C; D018184:Paramyxoviridae Infections / Q000473:pathology* / Q000821:virology; D012141:Respiratory Tract Infections / Q000473:pathology* / Q000821:virology; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D014764:Viral Proteins