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Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

ABSTRACT: We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 x 10(-3) to 7 x 10(-3) substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present.

SUBMITTER: Padhi A

PROVIDER: S-EPMC2643776 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

Padhi Abinash A Poss Mary M

Journal of virology 20081203 4

We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 x 10(-3) to 7 x 10(-3) substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes exa ...[more]

PMID: 19052092

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Project description:Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have been developed to decrease the economic losses caused by this virus. Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia. In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes. There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set. Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II. The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19(th) century and is evolving more slowly than other genotypes, which emerged in the 1960s. Despite vaccination efforts, genotype II viruses have experienced constant population growth to the present. In contrast, other contemporary genotypes showed population declines in the late 1990s. Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains. Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins.

Project description:The entry of avian metapneumovirus (aMPV) into host cells initially requires the fusion of viral and cell membranes, which is exclusively mediated by fusion (F) protein. Proteolysis of aMPV F protein by endogenous proteases of host cells allows F protein to induce membrane fusion; however, these proteases have not been identified. Here, we provide the first evidence that the transmembrane serine protease TMPRSS12 facilitates the cleavage of subtype B aMPV (aMPV/B) F protein. We found that overexpression of TMPRSS12 enhanced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. Subsequently, knockdown of TMPRSS12 with specific small interfering RNAs (siRNAs) reduced aMPV/B F protein cleavage, F protein fusogenicity, and viral replication. We also found a cleavage motif in the aMPV/B F protein (amino acids 100 and 101) that was recognized by TMPRSS12. The histidine, aspartic acid, and serine residue (HDS) triad of TMPRSS12 was shown to be essential for the proteolysis of aMPV/B F protein via mutation analysis. Notably, we observed TMPRSS12 mRNA expression in target organs of aMPV/B in chickens. Overall, our results indicate that TMPRSS12 is crucial for aMPV/B F protein proteolysis and aMPV/B infectivity and that TMPRSS12 may serve as a target for novel therapeutics and prophylactics for aMPV.ImportanceProteolysis of the aMPV F protein is a prerequisite for F protein-mediated membrane fusion of virus and cell and for aMPV infection; however, the proteases used in vitro and vivo are not clear. A combination of analyses, including overexpression, knockdown, and mutation methods, demonstrated that the transmembrane serine protease TMPRSS12 facilitated cleavage of subtype B aMPV (aMPV/B) F protein. Importantly, we located the motif in the aMPV/B F protein recognized by TMPRSS12 and the catalytic triad in TMPRSS12 that facilitated proteolysis of the aMPV/B F protein. This is the first report on TMPRSS12 as a protease for proteolysis of viral envelope glycoproteins. Our study will shed light on the mechanism of proteolysis of aMPV F protein and pathogenesis of aMPV.

Dataset Information

Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

Publications

Population dynamics and rates of molecular evolution of a recently emerged paramyxovirus, avian metapneumovirus subtype C.

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