TY - JOUR
T1 - Molecular phylogeny and evolutionary dynamics of influenza A nonstructural (NS) gene
AU - Xu, Jianpeng
AU - Zhong, Haizhen A.
AU - Madrahimov, Alex
AU - Helikar, Tomáš
AU - Lu, Guoqing
N1 - Funding Information:
This publication was made possible by NIH grant numbers R01 LM009985-01A1 . The authors also acknowledge the UCRCA, the University of Nebraska at Omaha, for continuous funding support to this research program. Constructive inputs from the editor and two reviewers that helped us to improve the quality of this current paper are highly appreciated.
PY - 2014/3
Y1 - 2014/3
N2 - While the nonstructural gene (NS) of the influenza A virus plays a crucial role in viral virulence and replication, the complete understanding of its molecular phylogeny and evolutionary dynamics remains lacking. In this study, the phylogenetic analysis of 7581 NS sequences revealed ten distinct lineages within alleles A and B: three host-specific (human, classical swine and equine), two reassortment-originated (A(H1N1)pdm09 and triple reassortment swine), one transmission-originated (Eurasian swine), and two geographically isolated avian (Eurasian/Oceanian and North American) for allele A and two geographically isolated avian (Eurasian/Oceanian and North American) for allele B. The average nucleotide substitution rates of the lineages range from 1.24×10-3 (equine) to 4.34×10-3 (A(H1N1)pdm09) substitutions per site per year. The selection pressure analysis demonstrated that the dN/dS ratio of the NS gene in A(H1N1)pdm09 lineage was higher than its closely related triple reassortant swine, which could be attributed to the adaptation to the new host and/or intensive surveillance after the inter-species transmission from swine to human. The positive selection sites were found in all lineages except the equine lineage and mostly in the NS1 region. The positive selection sites 22, 26, 226, 227 and 230 of the human lineage are significant because these residues participate in either forming the dimerization of the two RNA binding domain (RBD) monomers or blocking the replication of host genes. Residues at position 171 provide hydrophobic interactions with hydrophobic residues at p85β and thus induce viral cell growth. The lineages and evolutionary dynamics of influenza A NS gene obtained in this study, along with the studies of other gene segments, are expected to improve the early detection of new viruses and thus have the potential to enhance influenza surveillance.
AB - While the nonstructural gene (NS) of the influenza A virus plays a crucial role in viral virulence and replication, the complete understanding of its molecular phylogeny and evolutionary dynamics remains lacking. In this study, the phylogenetic analysis of 7581 NS sequences revealed ten distinct lineages within alleles A and B: three host-specific (human, classical swine and equine), two reassortment-originated (A(H1N1)pdm09 and triple reassortment swine), one transmission-originated (Eurasian swine), and two geographically isolated avian (Eurasian/Oceanian and North American) for allele A and two geographically isolated avian (Eurasian/Oceanian and North American) for allele B. The average nucleotide substitution rates of the lineages range from 1.24×10-3 (equine) to 4.34×10-3 (A(H1N1)pdm09) substitutions per site per year. The selection pressure analysis demonstrated that the dN/dS ratio of the NS gene in A(H1N1)pdm09 lineage was higher than its closely related triple reassortant swine, which could be attributed to the adaptation to the new host and/or intensive surveillance after the inter-species transmission from swine to human. The positive selection sites were found in all lineages except the equine lineage and mostly in the NS1 region. The positive selection sites 22, 26, 226, 227 and 230 of the human lineage are significant because these residues participate in either forming the dimerization of the two RNA binding domain (RBD) monomers or blocking the replication of host genes. Residues at position 171 provide hydrophobic interactions with hydrophobic residues at p85β and thus induce viral cell growth. The lineages and evolutionary dynamics of influenza A NS gene obtained in this study, along with the studies of other gene segments, are expected to improve the early detection of new viruses and thus have the potential to enhance influenza surveillance.
KW - Evolutionary dynamics
KW - Influenza A virus
KW - Lineage assignment
KW - Nonstructural (NS) gene
KW - Phylogeny
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U2 - 10.1016/j.meegid.2013.10.011
DO - 10.1016/j.meegid.2013.10.011
M3 - Article
C2 - 24161299
AN - SCOPUS:84896723201
VL - 22
SP - 192
EP - 200
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
SN - 1567-1348
ER -