title: Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade.
abstract: BACKGROUND
  Human metapneumovirus (HMPV) is a recently discovered paramyxovirus that is a major cause of respiratory infections worldwide.
  
  
  OBJECTIVE
  We aim to describe the molecular evolution of the HMPV F (fusion) and G (attachment) surface glycoproteins because they are targets for vaccines, monoclonal antibodies and antivirals currently in development.
  
  
  METHODS
  Nasopharyngeal aspirates were collected in children <3 years old with acute respiratory infection in Quebec City during 2001-2010. HMPV-positive samples (n = 163) underwent HMPV-F and -G gene sequencing. Furthermore, HMPV-F (n = 124) and -G (n = 217) sequences were obtained from GenBank and other studies. Evolutionary analyses (phylogenetic reconstruction, sequence identity, detection of recombination and adaptive evolution) were computed.
  
  
  RESULTS
  Sequences clustered into 5 genetic lineages (A1, A2a, A2b, B1 and B2). Multiple lineages circulated each year in Quebec City. With the exception of B1, each of the 5 subgroups was the predominant lineage during ≥1 season. The A1 lineage was not detected since 2002-2003 in our local cohort. There was no evidence of inter- or intragenic recombination. HMPV-F was highly conserved, whereas HMPV-G exhibited greater diversity. HMPV-F demonstrated strong evidence of purifying selection, both overall and in an abundance of negatively selected amino acid sites. In contrast, sites under diversifying selection were detected in all HMPV-G lineages (range, 4-15), all of which were located in the ectodomain.
  
  
  CONCLUSIONS
  Predominant circulating HMPV lineages vary by year. HMPV-F is highly constrained and undergoes significant purifying selection. Given its high genetic variability, we found a modest number of positively selected sites in HMPV-G.
authors.affiliation: Centre de recherche en infectiologie de l'Université Laval, Centre de recherche du CHUQ, Quebec City, Quebec, Canada; Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Jesse
authors.initials: J
authors.lastname: Papenburg
authors.forename: Julie
authors.initials: J
authors.lastname: Carbonneau
authors.forename: Sandra
authors.initials: S
authors.lastname: Isabel
authors.forename: Michel G
authors.initials: MG
authors.lastname: Bergeron
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Hamelin
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D029121:Metapneumovirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000821:virology; D018184:Paramyxoviridae Infections / Q000453:epidemiology / Q000821:virology*; D011446:Prospective Studies; D011792:Quebec / Q000453:epidemiology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014760:Viral Fusion Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: C484233:G glycoprotein, human metapneumovirus; D006023:Glycoproteins; D012367:RNA, Viral; D014760:Viral Fusion Proteins; D014764:Viral Proteins
keywords: Attachment (G) protein; CHUQ; Centre Hospitalier Universitaire de Québec; Fusion (F) protein; Genetic selection; HMPV; Human metapneumovirus; Phylogeny; RT-PCR; RTI; human metapneumovirus; respiratory tract infection; reverse-transcriptase polymerase chain reaction