title: Evolutionary dynamics analysis of human metapneumovirus subtype A2: genetic evidence for its dominant epidemic.
abstract: Human metapneumovirus (hMPV) is a respiratory viral pathogen in children worldwide. hMPV is divided into four subtypes: hMPV_A1, hMPV_A2, hMPV_B1, and hMPV_B2. hMPV_A2 can be further divided into hMPV_A2a and A2b based on phylogenetic analysis. The typical prevalence pattern of hMPV involves a shift of the predominant subtype within one or two years. However, hMPV_A2, in particular hMPV_A2b, has circulated worldwide with a several years long term high epidemic. To study this distinct epidemic behavior of hMPV_A2, we analyzed 294 sequences of partial G genes of the virus from different countries. Molecular evolutionary data indicates that hMPV_A2 evolved toward heterogeneity faster than the other subtypes. Specifically, a bayesian skyline plot analysis revealed that hMPV_A2 has undergone a generally upward fluctuation since 1997, whereas the other subtypes experienced only one upward fluctuation. Although hMPV_A2 showed a lower value of mean dN/dS than the other subtypes, it had the largest number of positive selection sites. Meanwhile, various styles of mutation were observed in the mutation hotspots of hMPV_A2b. Bayesian phylogeography analysis also revealed two fusions of diffusion routes of hMPV_A2b in India (June 2006) and Beijing, China (June 2008). Sequences of hMPV_A2b retrieved from GenBank boosted simultaneously with the two fusions respectively, indicating that fusion of genetic transmission routes from different regions improved survival of hMPV_A2. Epidemic and evolutionary dynamics of hMPV_A2b were similar to those of hMPV_A2. Overall, our findings provide important molecular insights into hMPV epidemics and viral variation, and explain the occurrence of an atypical epidemic of hMPV_A2, particularly hMPV_A2b.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, IPB, CAMS-Fondation Mérieux, Institute of Pathogen Biology (IPB), Peking Union Medical College (PUMC) & Chinese Academy of Medical Sciences (CAMS), Beijing, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Zichun
authors.initials: Z
authors.lastname: Xiang
authors.forename: Gláucia
authors.initials: G
authors.lastname: Paranhos-Baccalà
authors.forename: Guy
authors.initials: G
authors.lastname: Vernet
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
mesh_terms: D001499:Bayes Theorem; D002648:Child; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D029121:Metapneumovirus / Q000235:genetics*; D018184:Paramyxoviridae Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology*; D010802:Phylogeny