Computational analysis of adaptive antigenic mutations of the human influenza hemagglutinin for vaccine strain selection

Jared D. Rickert, Todd A. Herpy, Haizhen Zhong, Guoqing Lu
2012 International Journal of Bioinformatics Research and Applications  
The human influenza H1N1 and H3N2 viruses have been circulating over previous decades and are likely to continue due to antigenic mutations, with the hemagglutinin (HA) segment being the main target. However, adaptive evolution of the HA segment has not been fully understood because various selection pressures are involved. This paper aims to identify significant antigenic selection sites and link these sites and their respective amino acids to the structure changes over time. Strong positive
more » ... lection was detected in the HA of both H1N1 and H3N2, with four positively selected sites for H1N1 and eight positively selected sites for H3N2. Most of the positively selected codons showed patterns of directional evolution; and certain lineages that arose from positively selected codons appear to have finite lifespans. Two lineages have existed in the past decade in H1N1, with positive selection pressure occurring most recently at position 206 for the 1A lineage (2009 swine influenza) and positions 144, 190, and 192 for the 1B lineage. For H3N2, the loop regions near 157 and 225 appear to be the latest regions under selection pressure that vaccines may be able to target. By monitoring and linking the sequence changes with the tertiary structural changes, researchers will be in better position in term of picking appropriate vaccine strains and designing efficient vaccines and anti-viral drugs to combat this constantly mutating virus.
doi:10.1504/ijbra.2012.045978 pmid:22450272 fatcat:vv7glykvcrfydppym6zjzckynq