H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation

Annual seasonal influenza vaccines are composed of two influenza A strains representing the H1N1 and H3N2 subtypes, and two influenza B strains representing the Victoria and Yamagata lineages. Strains from these Influenza A and Influenza B viruses currently co-circulate in humans. Of these, strains associated with the H3N2 subtype are affiliated with severe influenza seasons. H3N2 influenza viruses pre-dominated during 3 of the last 5 quite severe influenza seasons. During the 2016/2017 flu season, the H3N2 component of the influenza vaccine exhibited a poor protective efficacy (∼28-42%) against preventing infection of co-circulating strains. Since their introduction to the human population in 1968, H3N2 Influenza viruses have rapidly evolved both genetically and antigenically in an attempt to escape host immune pressures. As a result, these viruses have added numerous N-linked glycans to the viral hemagglutinin (HA), increased the overall net charge of the HA molecule, changed their preferences in receptor binding, and altered the ability of neuraminidase (NA) to agglutinate red blood cells prior to host entry. Over time, these adaptations have made characterizing these viruses increasingly difficult. This review investigates these recent changes in modern H3N2 influenza viruses and explores the methods that researchers are currently developing in order to study these viruses.