Does the Evolutionary Nature of a Hemagglutinin and Neuraminidase Gene from Influenza A Virus (H3N2)
Paradis, N. (M.S., Rowan University); Elango, B. (H.S., Rowan University); St-Pierre, H. (B.S., Rowan University); Wu, C. (PhD, Rowan University)
Poster # 35
Influenza A H3N2 virus (H3N2, from hereon) is known to infect mammals (humans and pigs) and birds and can cause serious illness and death in children and the elderly. Thus, developing efficient vaccines is critical for preventing severe illness from H3N2 infections. H3N2 contains the receptor glycoproteins neuraminidase (NA) and hemagglutinin (HA), which are critical for the virus life cycle, and are considered antigenic determinants. Only HA antigens are used in current H3N2 vaccines. Including NA antigens in the vaccine could boost immunity against severe H3N2 infection. Understanding the molecular evolution of NA and HA at the gene and protein level is critical for optimizing vaccine design. While mainstream evolution theorists suggest H3N2 follows neutral selection (e.g., mutations are random and do not affect viral fitness), this does not explain the virus' quick adaptation to the human immune system and vaccine selection pressure. Near-Neutral Balanced Selection Theory (NNBST) was recently able to explain the apparent neutral evolution of the SARS-CoV-2 virus. This might also be the case for H3N2. NNBST was applied to >4K H3N2 NA and HA gene and protein sequences from human patients and were aligned against a reference sequence (GenBank: KY044136, A/Tennessee/03/2016(H3N2)). The relative substitution rate (c/µ) at each nucleotide/amino acid site was calculated for NA and HA with respect to the reference sequence, and the resulting c/µ probability distribution for each site generated an L-shaped distribution as predicted by NNBST. The number of non-synonymous substitutions (Ka, mutations change protein sequence) and synonymous substitutions (Ks, mutations do not change protein sequence), and the Ka/Ks ratio were also determined. The top 10 mutations indicating high positive/advantageous selection were determined from calculated c/µ and Ka/Ks and suggest decreased antibody binding and enhanced immune escape.