MECHANISM OF ANTIGENIC DRIFT IN INFLUENZA-VIRUS - AMINO-ACID-SEQUENCE CHANGES IN AN ANTIGENICALLY ACTIVE REGION OF HONG-KONG (H3N2) INFLUENZA-VIRUS HEMAGGLUTININ
MECHANISM OF ANTIGENIC DRIFT IN INFLUENZA-VIRUS - AMINO-ACID-SEQUENCE CHANGES IN AN ANTIGENICALLY ACTIVE REGION OF HONG-KONG (H3N2) INFLUENZA-VIRUS HEMAGGLUTININ
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DOI：
10.1016/0022-2836(81)90209-6
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发表时间：
1981-01-01
影响因子：
5.6
通讯作者：
WEBSTER, RG
中科院分区：
文献类型：
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作者：
LAVER, WG;AIR, GM;WEBSTER, RG
在流感病毒的抗原漂移过程中，抗原性的变化与大血凝素多肽HA1的氨基酸序列的变化有关。在用单抗筛选的10株H3N2型香港流感病毒变异株中，HA1第143位的脯氨酸残基变为丝氨酸、苏氨酸、亮氨酸或组氨酸。在其他变异中，天冬酰胺133变为赖氨酸，甘氨酸144变为天冬氨酸，丝氨酸145变为赖氨酸。除了最后一个碱基需要双碱基改变外，所有这些改变都可以通过RNA中的单碱基改变来实现。在1968-1977年间分离的香港流感野生株中，142-146残留物也发生了变化。通过与野生型病毒HA1的已知序列进行比较，检测了克隆变异体HA1中单一氨基酸序列的变化。HA1分子中包含110-140和230-255残基的两个不溶性胰蛋白酶多肽没有被检测到，这些区域可能发生的额外变化尚不清楚。为了确定在抗原漂移过程中是否发生了相同位置的顺序变化，使用针对其中Pro 143变为组氨酸或苏氨酸的变体上的新的抗原位点制备的抗体来选择这些变体的第二代变体。在第1例中，组氨酸旁边的甘氨酸残基(144)变为天冬氨酸，在第2例中，第143位的苏氨酸残基恢复为Pro，病毒恢复了野生型的抗原性。虽然单抗显示变异株与野生型病毒的抗原性有显著差异，但只有甘氨酸第144位变为天冬氨酸或丝氨酸第145位变为赖氨酸的变异株才能用异种兔或雪貂抗血清与野生型病毒区分开来。其他变异株，包括那些在HA1广泛分离的位置显示序列变化的变异株，无法与具有异质性抗血清的野生型区分开来。由HA1的142-146残基组成的区域的序列变化可能会影响血凝素分子上的一个重要的抗原点，但这些变化如何影响抗原性，或者该区域是否实际上形成抗原点的一部分，尚不清楚。
During antigenic drift in influenza viruses, changes in antigenicity are associated with changes in amino acid sequence of the large hemagglutinin polypeptide, HA1. In 10 variants of Hong Kong (H3N2) influenza virus selected with monoclonal antibodies, the proline residue at position 143 in HA1 changed to serine, threonine, leucine or histidine. In other variants, asparagine 133 changed to lysine, glycine 144 to aspartic acid and serine 145 to lysine. All these changes are possible by single base changes in the RNA except the last, which requires a double base change. Residues 142-146 also changed in field strains of Hong Kong influenza isolated between 1968-1977. The single amino acid sequence changes in HA1 of the monoclonal variants were detected by comparing the compositions of the soluble tryptic peptides from the variants with the known sequences of these peptides from wild-type virus. Two insoluble tryptic peptides, comprising residues 110-140 and 230-255 in the HA1 molecule, were not examined and additional changes which may occur in these regions are unknown. To determine whether sequential changes at the same position occurred during antigenic drift, antibody prepared against the new antigenic site on the variants in which proline 143 changed to histidine or threonine was used to select 2nd generation variants of these variants. In the 1st case, the glycine residue (144) next to the histidine changed to aspartic acid, and in the 2nd, the threonine residue at position 143 reverted to proline and virus regained the antigenicity of wild-type. Although monoclonal antibodies revealed dramatic antigenic differences between the variants and wild-type virus, only those variants with changes at position 144 of glycine to aspartic acid or at position 145 of serine to lysine could be distinguished from wild-type virus using heterogeneous rabbit or ferret antisera. The other variants, including those which showed sequence changes in widely separated positions of HA1, could not be distinguished from wild-type with heterogeneous antisera. Sequence changes in the region comprising residues 142-146 of HA1 may affect an important antigenic site on the hemagglutinin molecule, but how these changes affect the antigenic properties or whether this region actually forms part of the antigenic site, is not known.