Dataset Information

Use of AAScatterPlot tool for monitoring the evolution of the hemagglutinin cleavage site in H9 avian influenza viruses.

ABSTRACT:

Motivation

Viruses rapidly evolve due to their error-prone genome replication, and identifying which mutations are selected for during evolution is critical for virus surveillance efforts. Here we introduce a scatter plot tool (AAScatterPlot) that easily shows the selection and avoidance of certain protein mutations based on biochemical properties. We demonstrate its utility for monitoring the evolution of H9 avian influenza viruses from China between 2005 and 2015, particularly at the hemagglutinin (HA) proteolytic cleavage site (PCS) that can affect virus activation and pathogenicity.

Results

Given genome sequences, the AAScatterPlot tool compacts into a single plot, information about the hydropathy index, Van der Waals volume, chemical property and occurrence frequency of amino acid residues. The tool also shows the range of residues that could arise from a single point mutation in the genome, which can then be compared against the observed residues to identify mutation constraints. Through this approach, we found that the 2nd position towards the N-terminus side of the HA PCS (P2 position) avoided hydrophobic residues, whereas the P3 position avoided hydrophilic residues.

Availability and implementation

AAScatterPlot is available at https://github.com/WhittakerLab/AAScatterPlot.

Contact

gary.whittaker@cornell.edu.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Lee DW

PROVIDER: S-EPMC5859973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOngoing outbreaks of H5N1 highly pathogenic avian influenza (HPAI) viruses and the emergence of the genetic-related hemagglutinin (HA) gene of reassortant H5Nx viruses currently circulating in wild birds and poultries pose a great global public health concern. In this study, we comprehensively analyzed the genetic evolution of Thai H5N1 HA and neuraminidase (NA) genes between 2003 and 2010. The H5N1 Thailand virus clade 2.3.4 was also genetically compared to the currently circulating clade 2.3.4.4 of H5Nx viruses.MethodsFull-length nucleotide sequences of 178 HA and 143 NA genes of H5N1 viruses circulating between 2003 and 2010 were phylogenetically analyzed using maximum likelihood (ML) phylogenetic construction. Bayesian phylogenetic trees were reconstructed using BEAST analysis with a Bayesian Markov chain Monte Carlo (MCMC) approach. The maximum clade credibility (MCC) tree was determined, and the time of the most recent common ancestor (tMRCA) was estimated. The H5N1 HA nucleotide sequences of clade 2.3.4 Thailand viruses were phylogenetically analyzed using ML phylogenetic tree construction and analyzed for nucleotide similarities with various subtypes of reassortant H5Nx HA clade 2.3.4.4.ResultsML phylogenetic analysis revealed two distinct HA clades, clade 1 and clade 2.3.4, and two distinct NA groups within the corresponding H5 clade 1 viruses. Bayesian phylogenetic reconstruction for molecular clock suggested that the Thai H5N1 HA and NA emerged in 2001.87 (95% HPD: 2001.34-2002.49) and 2002.38 (95% HPD: 2001.99-2002.82), respectively, suggesting that the virus existed before it was first reported in 2004. The Thai H5N1 HA clade 2.3.4 was grouped into corresponding clades 2.3.4, 2.3.4.1, 2.3.4.2, and 2.3.4.3, and shared nucleotide similarities to reassortant H5Nx clade 2.3.4.4 ranged from 92.4-96.8%. Phylogenetic analysis revealed monophyletic H5Nx clade 2.3.4.4 evolved from H5N1 clade 2.3.4.ConclusionH5N1 viruses existed, and were presumably introduced and circulated in avian species in Thailand, before they were officially reported in 2004. HA and NA genes continuously evolved during circulation between 2004 and 2010. This study provides a better understanding of genetic evolution with respect to molecular epidemiology. Monitoring and surveillance of emerging variants/reassortants should be continued.