Evolutionary changes in influenza B are not primarily governed by antibody selection.

Abstract

Influenza B viruses evolve more slowly than human influenza A, but no reasons for the difference have been established. We have analyzed sequence changes in the hemagglutinin and neuraminidase of influenza B viruses (and have determined four hemagglutinin sequences, of B/Bonn/43, B/ USSR/100/83, B/Victoria/3/85, and B/Memphis/6/86) in relation to antigenic properties and compared these with similar analyses of variation in influenza A antigens. Independent of the slower rate of change in influenza B antigens, only approximately 30% of nucleotide changes in either the hemagglutinin or neuraminidase gene sequence result in amino acid changes in the protein, whereas in influenza A 50% of nucleotide changes result in altered amino acids. Thus, there is less selection for change, or less tolerance to change, in the influenza B antigens. This is similar to findings with influenza C and fndings with influenza A viruses that replicate in lower animals and birds and is closer to the type of variation found in other RNA viruses. We propose that human influenza A is unique in that it is the only virus group in which antibody selection dominates evolutionary change.

Evolution of the haemagglutinin-esterase gene of influenza C virus

“…The fact that the rate difference between influenza C and human influenza A viruses was larger in amino acids than in nucleotides suggests that there is less selection for change or less tolerance to change in type C virus H E than in type A virus HA. The driving force in evolution of the latter glycoprotein is believed to be antibody selection of antigenic variants (Air et al, 1990). Here it became evident that in the previously proposed immunodominant region on HE , there was little or no amino acid sequence divergence among the isolates on the same lineage although considerable divergence was seen among the isolates on different lineages.…”

Evolution and Ecology of Influenza A Viruses

“…This analysis suggests that prior to the divergence of influenza B virus, the ancestral avian virus HA subtypes had already diverged and that the B virus HA and the present 14 found in avian hosts, although the C viruses have been isolated from pigs and dogs; this has led to the suggestion that pigs serve as an alternate host reservoir for B and C viruses (51). Influenza B and C viruses exhibit slower evolution (especially the C viruses) than human influenza A viruses (2,22,23,130,196). Influenza C viruses cause only infrequent outbreaks of mild respiratory disease (74) and occur primarily in young children (124).…”

Persistence of a 1930 swine influenza A (H1N1) virus in Quebec

“…Antigenic masking, possibly by glycosylation, may permit continued circulation of influenza B strains (Air et al, 1990). A similar mechanism may also be operative in swine and human H1N1 influenza virus as they show variation throughout the HA gene and not specifically in the HAl domain (Sugita et al, 1991) and known antigenic sites as is observed with H3 influenza virus isolates (Bean et aI., 1992).…”

“…This probably indicates that drift gave rise to divergence of the nucleotide sequence of these viruses from an avian ancestor, but structural or functional constraints maintained an avian-like amino acid sequence. It has previously been suggested that drift in nucleotide sequence with little change in amino acids is indicative of minimal immunological selective pressure (Air et al, 1990;Sugita et al, 1991). Indeed immune selective pressure in swine H1N1 influenza virus appears to be weak as considerable genetic and antigenic stability has characterized most swine H1N1 influenza virus isolates since 1965 (Noble et al, 1993;Sheerar et al, 1989).…”

“…It has been proposed that drift in human influenza B virus, in contrast to human H3N2 influenza virus, does not depend on immune selective pressure (Air et al, 1990). Antigenic masking, possibly by glycosylation, may permit continued circulation of influenza B strains (Air et al, 1990).…”