Heterogeneity in the haemagglutinin gene and emergence of the highly pathogenic phenotype among recent H5N2 avian influenza viruses from Mexico

Heterogeneity in the haemagglutinin gene and emergence of the highly pathogenic phenotype among recent H5N2 avian influenza viruses from Mexico
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DOI:
10.1099/0022-1317-77-7-1493
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发表时间:
1996-07-01
影响因子:
3.8
通讯作者:
Perdue, ML
Perdue, ML
中科院分区:
医学3区
文献类型:
--
作者:
Garcia, M;Crawford, JM;Perdue, ML

文献摘要

被引文献

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最近在墨西哥中部爆发禽流感 (Al) 期间分离出的多种 H5N2 亚型病毒的血凝素 (HA) 编码区和蛋白水解裂解位点的分子变化已得到表征。 对 15 个月期间(1993 年 10 月至 1995 年 1 月)从 6 个中部州收集的 18 个分离株进行了测序。 18 个预测的 HA(1) 氨基酸序列均未被测序。 相同且变化不限于序列的特定区域,HA 的系统发育分析,序列显示出两个病毒谱系,指定为普埃布拉和哈利斯科,氨基酸序列变异高达 10.5%,核苷酸序列变异高达 6.2%。在监测期的后几个月,出现了 Al 的高致病性 (HP) 菌株,导致商业家禽致命疾病 Rocks,在分离的每个 HP 菌株中,HA 蛋白在没有胰蛋白酶的情况下在鸡胚成纤维细胞中被裂解,并且检测到早期非 HP 分离株中未发现的两个改变。在 HA 蛋白中,HP 菌株在氨基酸位置 324 处均具有谷氨酸 --> 赖氨酸取代,并插入精氨酸和赖氨酸作为新残基 325 和 326, 插入似乎是由于 HA(1) 编码区 965-970 核苷酸位置处的核苷酸序列 AAAGAA 重复所致,计算机辅助二级结构分析将插入目标置于预测的 RNA 茎环结构中,提出了聚合酶复制序列的机制。
Molecular changes in the haemagglutinin (HA)coding regions and proteolytic cleavage sites from multiple H5N2 subtype viruses isolated during a recent outbreak of avian influenza (Al) in central Mexico have been characterized, Eighteen isolates, collected during a 15 month period (October 1993 to January 1995) from six central states, were sequenced, None of the 18 predicted HA(1) amino acid sequences were identical and changes were not restricted to a specific region of the sequence, Phylogenetic analyses of the HA, sequences demonstrated two virus lineages, designated Puebla and Jalisco, with sequence variation as high as 10.5% for amino acid and 6.2% for nucleotide sequences, During the latter months of the surveillance period, highly pathogenic (HP) strains of Al emerged causing lethal disease in commercial poultry Rocks, In each of the HP strains isolated, the HA protein was cleaved in chicken embryo fibroblast cells in the absence of trypsin, and two alterations not found in earlier non-HP isolates were detected, In the HA protein, HP strains all had a glutamic acid --> lysine substitution at amino acid position 324 and an insertion of arginine and lysine as new residues 325 and 326, The insertion appears to be due to a duplication of the nucleotide sequence AAAGAA at nucleotide positions 965-970 of the HA(1)-coding region, Computer-assisted secondary structure analyses place the target for the insertion in a predicted RNA stem-loop structure, A mechanism is suggested by which the polymerase duplicates the sequence.