HA1 domain of influenza A (H3N2) viruses in Finland in 1989–1995: evolution, egg-adaptation and relationship to vaccine strains

Abstract

The HA1 gene sequences of 22 MDCK cell-derived influenza A (H3N2) strains, ten of their egg-derived counterparts and three vaccine strains were determined. Antigenic and sequence differences between the epidemic and vaccine strains were recorded, most striking in 1992/93; a minority of the amino acid differences in 1989-95 was involved in egg-adaptation. Changes in the assortment of amino acid substitutions produced during egg-adaptation of field strains may account for the difficulty encountered in isolating these viruses in embryonated eggs. Six revertant amino acids, characteristic of field strains prevalent in 1969-71 were recorded in 1994/95. Their genome sequence was interpreted to have been maintained over the interval years among low abundant sequences of the viral quasispecies. Potential changes of carbohydrate moieties were recorded in two glycosylation sites, suggesting that oligosaccharides at these sites are not necessarily advantageous for the H3N2 subtype virus currently.

Mutations at positions 186 and 194 in the HA gene of the 2009 H1N1 pandemic influenza virus improve replication in cell culture and eggs

“…Similar mutations in H1N1 swine flu isolates from the 1970 s increase growth in eggs and MDCK cells and reduce growth in swine [12]. Other groups have also demonstrated positive selective pressure on a variety of residues near the receptor binding site in H3N2 isolates, including variations at the same residues (186 and 194) [13-15] that we detected in our H1 S-OIV quasi-species. More recently, Glaser et al showed that a mutation at a nearby position (190) in the HA of the avian H1N1 virus that caused the 1918 pandemic was associated with this strain's adaptation to humans [16].…”

Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice

“…The amino acid sequence of the HA 1 of L phenotype viruses was identical to that of A/Beijing/353/89 as determined by [16] (GeneBank L76036). The entire HA 1 and HA 2 sequences of S and Mo viruses were identical and differed from L viruses by a single base substitution (A 814 →T) in HA 1 , giving rise to amino acid substitution Asn to Ser at residue 246.…”

“…Egg adaptation has been associated with a number of sequence changes that alter potential N-linked glycosylation sites on the HA, including the site at residue 246 of H3 subtype viruses [25-27] although loss of this site from particular H3 field strains was not associated with adaptation to growth in eggs [16]. In general terms, amino acid substitutions associated with egg-adapted variants cluster around the receptor-binding site on the HA molecule [28] and are likely to increase binding to Sia(α2,3)Gal moieties on cells of the chicken embryo chorio-allantoic membrane, the site of influenza virus replication in chicken eggs.…”

“…In the process of antigenic drift, the accumulation of glycosylation on the head of HA may shield the virus from pre-existing antibody in the human population [12,36] but increase sensitivity to collectin-mediated antiviral activities. While evidence indicates the maintenance of extensive glycosylation on the head of recent H3 viruses [37,38], loss of glycosylation from the HA of particular human isolates [16,39,40] argues for the existence of a fine balance between protection afforded by antibody and increased sensitivity to SP-D.…”

Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice

“…Furthermore, if lectin-mediated defenses decline in the elderly, an effect of glycosylation on virulence could be masked. Recently, Pyhälä et al (37) reported the loss of potential glycosylation sites (not associated with egg adaptation) at residues 246 and 278 of the HA of certain H3N2 field strains isolated in Finland in 1994 to 1995. Loss of glycosylation sites from HA was also found among H1N1 strains isolated in Finland and elsewhere in Europe in the period 1988 to 1993 (36) and among H1N1 strains isolated in 1983 to 1984 from specimens collected during persistent infection of an immunodeficient child (40).…”