Genetic Dynamic Analysis of the Influenza A H5N1 NS1 Gene in China

Wei, Kaifa; Chen, Yanhui; Lin, Yi; Pan, Yutian

doi:10.1371/journal.pone.0101384

Cited by 8 publications

(8 citation statements)

References 76 publications

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“…More specifically, the HA, NA and NS1 genes displayed more adaptive pressures than the other segments. Greater d N / d S in the NS1 gene could be indicative of antagonizing host type I interferon innate immune response (Wei, Chen, Lin, & Pan, ). However, it should also be noted that the mean d N / d S value (0.40; 95% HPD 0.35–0.46) of the NS1 in our analysis is comparable with other a previous study of EA viruses from swine in Hong Kong (0.30; 95% HPD 0.23–0.39) that only included viruses sampled from 2001 to 2010 (Vijaykrishna et al., ).…”

Section: Resultsmentioning

confidence: 99%

Adaptive evolution during the establishment of European avian‐like H1N1 influenza A virus in swine

Joseph

Vijaykrishna

Smith

et al. 2017

Evolutionary Applications

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An H1N1 subtype influenza A virus with all eight gene segments derived from wild birds (including mallards), ducks and chickens, caused severe disease outbreaks in swine populations in Europe beginning in 1979 and successfully adapted to form the European avian‐like swine (EA‐swine) influenza lineage. Genes of the EA‐swine lineage that are clearly segregated from its closest avian relatives continue to circulate in swine populations globally and represent a unique opportunity to study the adaptive process of an avian‐to‐mammalian cross‐species transmission. Here, we used a relaxed molecular clock model to test whether the EA‐swine virus originated through the introduction of a single avian ancestor as an entire genome, followed by an analysis of host‐specific selection pressures among different gene segments. Our data indicated independent introduction of gene segments via transmission of avian viruses into swine followed by reassortment events that occurred at least 1–4 years prior to the EA‐swine outbreak. All EA‐swine gene segments exhibit greater selection pressure than avian viruses, reflecting both adaptive pressures and relaxed selective constraints that are associated with host switching. Notably, we identified key amino acid mutations in the viral surface proteins (H1 and N1) that play a role in adaptation to new hosts. Following the establishment of EA‐swine lineage, we observed an increased frequency of intrasubtype reassortment of segments compared to the earlier strains that has been associated with adaptive amino acid replacements, disease severity and vaccine escape. Taken together, our study provides key insights into the adaptive changes in viral genomes following the transmission of avian influenza viruses to swine and the early establishment of the EA‐swine lineage.

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Section: Resultsmentioning

confidence: 99%

Adaptive evolution during the establishment of European avian‐like H1N1 influenza A virus in swine

Joseph

Vijaykrishna

Smith

et al. 2017

Evolutionary Applications

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“…The site 237 detected in the PA protein is essential for determining viral replication and polymerase activity (Hu et al., ). In HA, positions 138 and 140 are recognized as the targets for neutralizing antibodies, whereas the site 340 detected in the NA protein is located in the B‐cell antigenic regions (Wei et al., ). Furthermore, position 209, which contributed to the altered virulence and determined the effect on pathogenicity (Pu et al., ), was a positive selected site in NS1 protein (Wei et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…In HA, positions 138 and 140 are recognized as the targets for neutralizing antibodies, whereas the site 340 detected in the NA protein is located in the B‐cell antigenic regions (Wei et al., ). Furthermore, position 209, which contributed to the altered virulence and determined the effect on pathogenicity (Pu et al., ), was a positive selected site in NS1 protein (Wei et al., ). However, the biological function of the positively selected sites in PB1 and MP was not well understood.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic Analysis and Functional Characterization of the Influenza A H5N1 PB2 Gene

Wei

Liu

2015

Transbound Emerg Dis

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Highly pathogenic avian influenza (HPAI) H5N1 viruses are endemic in poultry and cause continued inter-species transmission to human in Asia, such as China and Vietnam, leading to pandemic concerns and socio-economic challenges. Phylogenetic analysis of H5N1 viruses isolated from China and Vietnam during 2001-2012 showed that several geographically distinct sublineages have become established in these two countries. Subsequently, we reassigned HPAI H5N1 viruses into three distinct groups to reveal the intrasubtype reassortment. Apart from six reassortants detected here, we found that several viral strains showed signals for homologous recombination within PB2 and PB1 genes, suggestive of the fluidity of the H5N1 virus gene pool. Furthermore, sequenced-based analyses revealed that the viral polymerase displayed a higher level of genetic polymorphism but associated with lower substitution rate when compared with those of other gene segments. In addition, the selection pressure analysis indicated that purifying selection was predominant in eight genomic segments especially in the polymerase complex. However, the site-by-site analysis helped to detect 14 positively selected sites in the PB1, PA, HA, NA, MP and NS proteins. Despite the fact that PB2 protein of H5N1 viruses was highly conserved at the amino acid level, eleven adaptive mutations were still observed in the protein. Further comparative structural analysis of the K627E mutation indicated that there were no structural differences between the variants, which possessed either PB2-627E or PB2-627K. Transcriptomic analysis suggested the non-mitochondrial PB2 protein of H5N1 virus that forms a stable complex with the mitochondrial antiviral signalling protein (MAVS, also known as IPS-1, VISA or Cardif) can induce interferon-beta (IFN-β) expression, but the substitution (PB2-K627E) is not the sole determinant of the RIG-I-like receptors (RLR) signalling components induction in Calu-3 cells.

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“…Eight genome segment alignment data sets were found to be free of homologous recombination. Putative reassortant viruses were preliminarily identified by their topological incongruities among all phylogenies (Wei et al., ). The reassortant viruses were further investigated with two small subsets of full genome sequences of H5N1 strains isolated from Indonesia and Vietnam.…”

Section: Methodsmentioning

confidence: 99%

Tracking the Evolution in Phylogeny, Structure and Function of H5N1 Influenza Virus PA Gene

Wei

Lin

et al. 2014

Transbound Emerg Dis

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Summary Highly pathogenic avian influenza (HPAI) H5N1 viruses have severely affected the poultry industry of Vietnam and Indonesia. The outbreaks of HPAI H5N1 viruses continue to pose a serious threat to public health, which have profound impacts on public health. In this study, we presented phylogenetic evidences for five reassortants among HPAI H5N1 viruses sampled from Vietnam and Indonesia during 2003–2013 and found that reassortment events occurred more frequently in the three gene segments (PB1, PA and HA) than in the remaining five gene segments (PB2, NA, NP, NS and MP). The sequence‐based analyses have revealed that the PA protein displays high levels of DNA sequence polymorphism and variability than other internal proteins. Seven positive selection sites were detected in PA proteins, which ranked second only to the surface glycoproteins. Structure‐based comparative analysis of PA proteins showed a remarkable sequence conservation between the high‐pathogenic, low‐pathogenic and reassortant viruses, indicating that PA appears to be a potential antiviral target. Furthermore, by analysing the published data, we compared the differential expression of genes involved in RIG‐I‐ and MAVS‐mediated intracellular type I interferon (IFN)‐inducing pathway between the VN3028IIcl2‐infected, IDN3006‐infected and IDN3006/PA‐infected groups. Our analyses indicated that the inhibitory effect of the PA protein on MAVS was not strong. In addition, transcriptional levels of 33 mitochondrial proteins involved in the induction of apoptosis have significantly increased, suggesting that PA may play an important role in apoptosis signalling pathway.

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Genetic Dynamic Analysis of the Influenza A H5N1 NS1 Gene in China

Cited by 8 publications

References 76 publications

Adaptive evolution during the establishment of European avian‐like H1N1 influenza A virus in swine

Adaptive evolution during the establishment of European avian‐like H1N1 influenza A virus in swine

Phylogenetic Analysis and Functional Characterization of the Influenza A H5N1 PB2 Gene

Tracking the Evolution in Phylogeny, Structure and Function of H5N1 Influenza Virus PA Gene

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