Why do influenza virus subtypes die out? A hypothesis

Abstract

Novel pandemic influenza viruses enter the human population with some regularity and can cause disease that is severe and widespread. The emergence of novel viruses, historically, has often been coupled with the disappearance of existing seasonal virus strains. Here, we propose that the elimination of seasonal strains during virus pandemics is a process mediated, at the population level, by humoral immunity. Specifically, we suggest that infection with a novel virus strain, in people previously exposed to influenza viruses, can elicit a memory B cell response against conserved hemagglutinin stalk epitopes and/or neuraminidase epitopes. The anti-stalk and/or anti-neuraminidase antibodies then act to diminish the clinical severity of disease caused by novel influenza viruses and to eliminate seasonal virus strains.

FIG 1

Influenza A viruses circulating in the human population and induction of cross-protective antibodies by pandemic viruses. (A) H1N1 indicates virus with hemagglutinin subtype 1 and neuraminidase subtype 1. H2N2 and H3N2 indicate viruses with hemagglutinin subtype 2 and neuraminidase subtype 2 and hemagglutinin subtype 3 and neuraminidase subtype 2, respectively. pH1N1 indicates the novel swine origin virus first isolated in 2009. (B) Antibody response in the human population, which we propose to have contributed to the elimination of existing seasonal influenza virus strains. Gr1, group 1 subtype; Gr2, group 2 subtype.

FIG 2

Representation of the major antigenic differences between hemagglutinin subtypes. Group 1 subtypes, such as H1 and H2, share a conserved stalk domain (dark gray); group 2 subtypes, such as H3, have a stalk domain that is structurally different (light gray) from the group 1 stalk. The globular heads of the different hemagglutinin subtypes are structurally distinct (green/red/blue).