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. 2009 Jun;7(1-2):47-56.
doi: 10.1016/S1672-0229(08)60032-7.

Role of positive selection pressure on the evolution of H5N1 hemagglutinin

Venkata R S K Duvvuri  1 , Bhargavi Duvvuri, Wilfred R Cuff, Gillian E Wu, Jianhong Wu
Affiliations

Role of positive selection pressure on the evolution of H5N1 hemagglutinin

Venkata R S K Duvvuri et al. Genomics Proteomics Bioinformatics. 2009 Jun.

Abstract

The surface glycoprotein hemagglutinin (HA) helps the influenza A virus to evade the host immune system by antigenic variation and is a major driving force for viral evolution. In this study, the selection pressure on HA of H5N1 influenza A virus was analyzed using bioinformatics algorithms. Most of the identified positive selection (PS) sites were found to be within or adjacent to epitope sites. Some of the identified PS sites are consistent with previous experimental studies, providing further support to the biological significance of our findings. The highest frequency of PS sites was observed in recent strains isolated during 2005-2007. Phylogenetic analysis was also conducted on HA sequences from various hosts. Viral drift is almost similar in both avian and human species with a progressive trend over the years. Our study reports new mutations in functional regions of HA that might provide markers for vaccine design or can be used to predict isolates of pandemic potential.

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Figures

Figure 1
Figure 1
Comparative representation of the distribution of PS sites in avian and human H5N1 HA sequences.
Figure 2
Figure 2
Average frequencies of positively selected amino acids of avian and human isolates of H5N1 virus from 1996 to 2007. Group I: Avian (1996, 1997) and Human (1997, 1998); Group II: Avian (1999, 2000, 2001); Group III: Avian (2002, 2003, 2004) and Human (2003, 2004); Group IV: Avian (2005, 2006, 2007) and Human (2005, 2006, 2007); Cum: Cumulative avian and human groups.
Figure 3
Figure 3
A. Protein-based evolutionary relationship of H5N1 (avian, human, swine and other animals), H5N2, H5N3, H5N8 and H5N9 (avian) HA genes using neighbor-joining tree construction. Bootstrap values of 2,500 replications are shown on major branches.
Figure 3
Figure 3
B. Nucleotide-based evolutionary relationship of H5N1 (avian, human, swine and other animals), H5N2, H5N3, H5N8 and H5N9 (avian) HA genes using neighbor-joining tree construction. Bootstrap values of 2,500 replications are shown on major branches.
Figure 4
Figure 4
Evolutionary rates for nucleic acids and proteins of H5N1 HA isolated from avian and human hosts. Evolutionary rate is estimated by regression of year of isolation against branch distance from the common origin node of the nucleotide and amino acid.
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