Key result
The hMPV_A2 subtype evolved toward heterogeneity faster than other subtypes and had the largest number of positive selection sites, explaining its atypical long-term dominant epidemic.
Observational (n=294)
Evolutionary dynamics and genetic transmission route fusions explain the atypical, long-term high epidemic behavior of hMPV_A2.
May guide hMPV surveillance; hypothesis-generating for subtype-specific epidemic drivers.
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.
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Li et al. (2012) conducted an observational in Human metapneumovirus (hMPV) infection (n=294). hMPV_A2 subtype vs. Other hMPV subtypes (A1, B1, B2) was evaluated on Evolutionary rate and positive selection sites. The hMPV_A2 subtype evolved toward heterogeneity faster than other subtypes and had the largest number of positive selection sites, explaining its atypical long-term dominant epidemic.
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