Webster R G, Laver W G, Air G M, Ward C, Gerhard W, van Wyke K L
Ann N Y Acad Sci. 1980;354:142-61. doi: 10.1111/j.1749-6632.1980.tb27964.x.
Monoclonal antibodies to the hemagglutinin molecule of the Hong Kong variant, Mem/1/71 (H3N2), influenza virus were used to study antigenic drift in the H3N2 subtype of influenza viruses. Antigenic variants of Mem/1/71 (H3N2) were selected after a single passage of the virus in chick embryos in the presence of monoclonal antibody. The variants showed a marked reduction in the ability to react with the monoclonal antibody used in selection. The monoclonal antibodies could be divided into three groups based on their reactions with the variants, providing evidence for at least three nonoverlapping antigenic areas on the hemagglutinin molecule. Amino acid analysis of tryptic peptides of the hemagglutinin from these variants showed that a single amino acid substitution in the heavy polypeptide chain (HA1) of the hemagglutinin molecule accounted for the reduced antibody interactions, and that variants from each group exhibited sequence changes in different areas of the molecule. Sequence changes were also detected in the HA1 polypeptides of naturally occurring H3N2 variants, but in most cases the changes in the monoclonal antibody selected variants were different from the field strains. Antigenic analysis showed that most of the variants selected with monoclonal antibody could not be distinguished from parental viruses with heterogeneous sera, suggesting that they are probably epidemiologically irrelevant. One variant, however, could be distinguished from parental virus with heterogeneous sera. This variant showed a change in sequence at residue 144 of the HA1 polypeptide from glycine in the parent to aspartic acid in the variant. Similar substitutions have been found in naturally occurring variants at this position. These studies suggest that some amino acid substitutions are more important than other for producing viruses with epidemiological potential. Antigenic analysis of naturally occurring H3N2 strains with monoclonal antibodies established that two variants co-circulated in 1968; Hong Kong/1/68 being distinguishable from Aichi/2/68 in at least two antigenic areas. It would appear that there may have been two separate lineages of H3N2 viruses, Hong Kong/1/68 giving rise to variants in England and Aichi/2/68 to variants in USA and Australia.
针对香港变异株Mem/1/71（H3N2）流感病毒血凝素分子的单克隆抗体被用于研究流感病毒H3N2亚型中的抗原漂移。在鸡胚中，病毒在单克隆抗体存在的情况下传代一次后，筛选出了Mem/1/71（H3N2）的抗原变异株。这些变异株与筛选时所用单克隆抗体反应的能力显著降低。根据单克隆抗体与变异株的反应，可将其分为三组，这为血凝素分子上至少三个不重叠的抗原区域提供了证据。对这些变异株血凝素的胰蛋白酶肽段进行氨基酸分析表明，血凝素分子重多肽链（HA1）中的单个氨基酸替换导致了抗体相互作用的减少，并且每组变异株在分子的不同区域表现出序列变化。在自然发生的H3N2变异株的HA1多肽中也检测到了序列变化，但在大多数情况下，单克隆抗体筛选出的变异株中的变化与野外毒株不同。抗原分析表明，大多数用单克隆抗体筛选出的变异株无法用异源血清与亲本病毒区分开来，这表明它们可能在流行病学上不相关。然而，有一个变异株能用异源血清与亲本病毒区分开来。该变异株HA1多肽第144位残基的序列从亲本中的甘氨酸变为变异株中的天冬氨酸。在自然发生的变异株中该位置也发现了类似的替换。这些研究表明，对于产生具有流行病学潜力的病毒，某些氨基酸替换比其他替换更重要。用单克隆抗体对自然发生的H3N2毒株进行抗原分析确定，1968年有两种变异株共同流行；香港/1/68在至少两个抗原区域可与爱知/2/68区分开来。似乎可能有两个独立的H3N2病毒谱系，香港/1/68在英国产生变异株，爱知/2/68在美国和澳大利亚产生变异株。
