Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥4,700,000 (Direct Cost: ¥4,700,000)
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Research Abstract |
1. We produced a total of 37 monoclonal antibodies (MAbs) against the hemagglutinin-esterase (HE) protein of influenza C virus, ten with hemagglutination-inhibition, hemolysis inhibition, and neutralization activities (group A) and 27 without the activities (group B). Operational and topological analyses with these antibodies revealed that at least nine non-over-lapping or partially overlapping antigenic sites were present on the HE protein, four recognized by group A MAbs (A-1-A-4) and five by group B (B-1 - B-5). 2. Neutralization-resistant variants of influenza C virus were selected with group A MAbs against four different antigenic sites (A-1-A-4), and their HE genes were sequenced to identify amino acid residues important for the integrity of each site. Although variants for antigenic site A-2 had a change at position 367, all substitutions in the variants for sites A-1, A-3, and A-4 occurred in the central region of the HE1 subunit spanning amino acid position 178 to 283. It was a
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lso found that many of the variants selected with antibodies to sites A-1 and A-3 were clustered within or near one of the three variable regions revealed previously by comparing amino acid sequences of the HEs among various influenza C isolates, which supports the notion that influenza C virus, like human influenza A viruses, may be exposed to a significant amount of immunological pressure. 3. Sixteen influenza C strains isolated in Yamagata City between April 1988 and May 1990 were compared by antigenic analysis with anti-HE HAbs and oligonucleotide mapping of total vRNAs. The results showed that the isolates could be classified into two groups : seven isolates were closely related to the influenza C strain isolated in 1981 in Aichi prefecture, (Aichi/1/81), and the remaining nine were very similar to the strain isolated in the same year in Yamagata prefecture (Yamagata/1/81). Thus it appears that two evolutionary linages of influenza C virus, different markedly from each other in the antigenicity of HE, were selected presumably by immunological pressure and became predominant at least in Yamagata city. Less
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