Crawford-Miksza L K, Schnurr D P
Viral and Rickettsial Disease Laboratory, California Department of Health Services, Berkeley 94704, USA.
Virology. 1996 Oct 15;224(2):357-67. doi: 10.1006/viro.1996.0543.
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 surface regions of the major viral coat protein confers a distinct survival advantage to this family of viruses.
通过研究18种血清学相关的D亚属血清型和3种中间型之间的进化关系，并确定单一血清型AV 48在6年期间艾滋病患者临床分离株中的突变率，对艾滋病相关腺病毒（AV 43 - AV 49）的起源进行了调查。测定了六邻体蛋白保守区和七个高变区（HVRs）、pVI核心蛋白信号肽以及两个基因之间非编码区的核苷酸序列。在AV 48分离株中，6年期间碱基错配率为每10000个碱基3.2个。在HVR 7的短直接重复序列之间，一个分离株中发生了6个碱基的缺失。在D亚属血清型中，pVI肽、六邻体蛋白5'非编码区和六邻体蛋白的前187个碱基的突变率极低。在3个菌株中，非编码区聚嘌呤延伸段的短直接重复序列之间出现了2个和3个碱基的小缺失。突变随着与HVRs的接近而增加。在HVR 1、2、4、5和7内，变异包括广泛的染色体内非法重组，包括短直接重复序列之间的缺失、重复聚嘌呤延伸段中的插入和重复以及大量碱基替换。所有血清型和中间型至少有一个非法重组事件不同，只有一个例外。我们得出结论，AV血清型进化是由非法重组事件（抗原转变）驱动的，同时伴有单碱基突变（抗原漂移），并且HVRs是这两者的“热点”。这些事件可以通过单链DNA复制过程中AV DNA聚合酶在重复聚嘌呤延伸段中的滑动错配来解释。主要病毒衣壳蛋白表面区域的这种可变性赋予了该病毒家族独特的生存优势。
