Adenovirus serotype evolution is driven by illegitimate recombination in the hypervariable regions of the hexon protein
Adenovirus serotype evolution is driven by illegitimate recombination in the hypervariable regions of the hexon protein
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DOI：
10.1006/viro.1996.0543
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发表时间：
1996-10-15
期刊：
影响因子：
3.7
通讯作者：
Schnurr, DP
中科院分区：
文献类型：
--
作者：
CrawfordMiksza, LK;Schnurr, DP
通过检测18个血清学相关的D亚型和3个中间体之间的进化关系，以及6年来艾滋病患者临床分离株中单一血清型AV48的变异率，探讨了艾滋病相关腺病毒(AV43-AV49)的起源。测定了Hexon蛋白、PVI核心蛋白信号肽和两个基因之间的非编码区的保守区和7个高变区的核苷酸序列。在AV48株中，6年间碱基错合率为3.2/万个碱基。在亚型D亚型中，PVI多肽、5‘Hexon非编码区和Hexon蛋白前187个碱基的突变率极低。在非编码区，有3个菌株发生了短重复序列之间的2个和3个碱基的小片段缺失，突变随着HVR的临近而增加。在hvr1、2、4、5和7中，变异包括广泛的染色体内非法重组，包括短直接重复之间的缺失，重复多嘌呤延伸中的插入和复制，以及大量的碱基替换。除了一个例外，所有的血清型和中间体至少有一个不合法的重组事件。我们的结论是，病毒血清型的进化是由非法重组事件(抗原漂移)驱动的，符合单碱基突变(抗原漂移)，并且HVR是两者的“热点”。这些事件可以解释为在单链DNA复制过程中，病毒DNA聚合酶在重复的多聚嘌呤延伸中的滑移-错位。主要病毒外壳蛋白表面区域的这种变异性赋予了这一病毒家族独特的生存优势。(C)1996年学术出版社。
The origin of AIDS-associated adenoviruses (AV 43-AV 49) was investigated by examining evolutionary relationships among 18 serologically related subgenus D serotypes and 3 intermediates and determining the mutation rate of a single serotype, AV 48, among clinical isolates from AIDS patients over a 6-year period. Nucleotide sequence of conserved and seven hypervariable regions (HVRs) of the hexon protein, the pVI core protein signal peptide, and noncoding region between the two genes was determined. Among AV 48 isolates the base misincorporation rate was 3.2 per 10,000 bases over 6 years. A 6-bp deletion occurred in one isolate between short direct repeats in HVR 7, Among subgenus D serotypes mutation rates were extremely low in the pVI peptide, the 5' hexon noncoding region, and first 187 bases of hexon protein. Small 2-and 3-bp deletions between short direct repeats in a polypurine stretch in the noncoding region occurred in 3 strains, Mutation increased with proximity to the HVRs. Within HVR 1, 2, 4, 5, and 7 variability consisted of extensive intrachromosomal illegitimate recombination, including deletions between short direct repeats, insertions and duplications in repetitive polypurine stretches, and numerous base substitutions. All serotypes and intermediates differed by at least one illegitimate recombination event, with one exception. We conclude that AV serotype evolution is driven by illegitimate recombination events (antigenic shift), concommitant with single base mutation (antigenic drift), and that the HVRs are ''hot spots'' for both. These events could be explained by slippage-misalignment of the AV DNA polymerase in repetitive polypurine stretches during single-strand DNA replication. This mutability in the suriace regions of the major viral coat protein confers a distinctsurvival advantage to this family of viruses. (C) 1996 Academic Press, Inc.