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To study the neutralizing epitopes of influenza B virus Victoria group strains, two monoclonal antibodies (MAbs) were used to select antigenic variants of the virus. MAbs 10B8 and 8E6 were found to react with B/Victoria group strains in three tests, peroxidase-antiperoxidase staining, haemagglutination inhibition and neutralization tests ; no reactivity with B/Yamagata group strains was observed. Analysis of the deduced amino acid sequences of 10B8-induced variants identified a single amino acid deletion at residue 165 or 170, as well as a single amino acid substitution at residues 164 (Asp Tyr), 165 (Asn Ser or Thr) or 203 (Lys Thr or Asn). A single amino acid substitution at residue 241 (Pro Ser) was observed in 8E6-induced variants. Three-dimensional analysis showed that the epitopes for both MAbs were situated in close proximity to each other. Since B/Yamagata group strains are characterized by amino acid deletions at residues 164-166, the epitope for MAb 10B8 is strictly specific for B/ Victoria group strains.Influenza is one of the most important infectious diseases in both industrial and developing countries. Influenza B virus strains cause epidemics in humans as H1 and H3 subtype strains of influenza A virus. Compared with influenza A virus, influenza B virus is characterized by a low rate of antigenic change ; genetic reassortment, insertion and deletion are responsible for its evolution (Lindstrom et al., 1999 ;McCullers et al., 1999). Influenza B virus strains are divided into two large phylogenic trees : one group is represented by B\Victoria\2\87 and the other is represented by B\ Yamagata\16\88 (Kanegae et al., 1990). Virus strains of the B\Victoria group were dominant all over the world in the 1980s, while the B\Yamagata group strains became dominant in the early 1990s. However, in the mid 1990s, B\Victoria group strains re-emerged in South China. Since the 1996-1997 epidemic season in Japan, two distinctly different antigenic groups of influenza B viruses have been isolated from clinical specimens during the same epidemic season (Nakagawa et al., 1999 ;Nerome et al., 1998). We obtained monoclonal antibodies (MAbs) specific for influenza B virus and used them for peroxidase-antiperoxidase (PAP) staining. When MAbs specific for either the nucleoprotein or the matrix protein were used, both the B\Victoria and B\Yamagata group strains were detected equally well. When MAb 10B8, which is specific for the haemagglutinin (HA) molecule, was used for PAP staining, the two strains were clearly distinguishable (Nakagawa et al., 1999). MAb 10B8 not only reacted with all B\Victoria group strains in PAP staining, but also showed strong activity in haemagglutination inhibition (HI) and neutralization (NT) tests. MAb 8E6 reacted with about 70 % of the B\Victoria group strains isolated during the 1996-1997 season in PAP staining and showed HI and NT test reactivity with 45 %. Neither MAb reacted with the B\Yamagata group strains (Nakagawa et al., 2000).In order to study neutralizing epitopes that are specific for ...

During the 1998-1999 influenza season, two distinct influenza B virus Yamagata group strains were isolated from the patients of a private clinic. Each responded differently to monoclonal antibodies (Mabs) 5H4 and 8B3 on staining, and hemagglutination inhibition and neutralizing tests. When the analysis of nucleotide sequences was undertaken, the identity of deduced amino acid sequences of the HA1 region was 94%, which suggested that they derived from different strains. They were termed 5H4-responding strains and 5H4-nonresponding strains, respectively. The analysis of laboratory-induced antigenic variants suggested that the amino acid at position 149 is important to the reactivity to 5H4. This residue was "Arg" in 5H4-responding strains and "Lys" in nonresponding strains. During the 1998-1999 season, a total of 100 influenza B virus strains were isolated and 5H4-responding strains were the major type (94 strains). In the 1999-2000 influenza season, only two influenza B virus strains were isolated. Neither responded to 5H4. However, analysis of the deduced amino acid sequences of the HA1 region suggested that one of the two strains was derived from the 5H4-responding strains of the previous season. The amino acid residue at position 149 was "Lys" in place of "Arg." These observations suggested that 5H4-nonresponding strains will increase in coming seasons.

For almost 20 years, the neutralizing-epitope site specific for influenza B virus Victoria group isolates was conserved at the "tip" of the hemagglutinin molecule; however, it was not detected in half of the isolates from the 2002-2003 epidemic in Japan. Amino acid substitutions (D164E or N165K) were observed at the "tip," and the epitope was altered. The viral antigenicities were affected, and human antibodies did not substantially inhibit the hemagglutination in the hemagglutination inhibition tests. It is suspected that such variants will be important in future epidemics.