Yamada T, Wheeler C M, Halpern A L, Stewart A C, Hildesheim A, Jenison S A
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131, USA.
J Virol. 1995 Dec;69(12):7743-53. doi: 10.1128/JVI.69.12.7743-7753.1995.
Human papillomavirus type 16 (HPV16) nucleotide sequence variations in the E6 (nucleotide positions [nt] 104 to 559), L2 (nt 4272 to 5657), and L1 (nt 5665 to 7148) open reading frames (ORFs), and the long control region (nt 7479 to 7842), were examined in 29 selected United States isolates. Of 3,690 nucleotide positions, 129 (3.5%) varied. The maximum pairwise distance was 66 nucleotide differences, or 1.8%. Nucleotide variations within different genome segments were phylogenetically compatible, and nucleotide changes within E6, L2, and L1 contained phylogenetic information beyond that provided in the long control region. Most isolates were classified as members of HPV16 lineages that have been described previously. However, two novel phylogenetic branches were identified. The L2 ORF was the most variable coding segment. L2 synonymous and nonsynonymous nucleotide changes were distributed asymmetrically. The amino-terminal half of the L2 protein was remarkably conserved among all isolates, suggesting that the region is under evolutionary constraint. The amino-terminal region of the E6 ORF was relatively varied, especially at E6 amino acid positions 10 and 14. Several amino acid difference in the L1 ORF were observed between lineages. Forty-nine amino acid variations across all sequenced coding regions were observed. These amino acid differences may be relevant to differences in the generation of humoral or cell-mediated immune responses to HPV16 variants. Our data form a basis for considering HPV16 sequence variation in the rational design of vaccine strategies and as an epidemiologic correlate of cervical cancer risk.
对29株从美国挑选出的人乳头瘤病毒16型（HPV16）分离株的E6（核苷酸位置[nt]104至559）、L2（nt 4272至5657）和L1（nt 5665至7148）开放阅读框（ORF）以及长控制区（nt 7479至7842）中的核苷酸序列变异进行了检测。在3690个核苷酸位置中，有129个（3.5%）发生了变异。最大成对距离为66个核苷酸差异，即1.8%。不同基因组片段内的核苷酸变异在系统发育上是兼容的，并且E6、L2和L1内的核苷酸变化所包含的系统发育信息超出了长控制区所提供的信息。大多数分离株被归类为先前已描述的HPV16谱系成员。然而，鉴定出了两个新的系统发育分支。L2 ORF是变异最大的编码片段。L2同义核苷酸和非同义核苷酸变化分布不对称。L2蛋白的氨基末端在所有分离株中都非常保守，表明该区域受到进化限制。E6 ORF的氨基末端区域相对多变，尤其是在E6氨基酸位置10和14处。在谱系之间观察到L1 ORF中有几个氨基酸差异。在所有测序的编码区域共观察到49个氨基酸变异。这些氨基酸差异可能与针对HPV16变体的体液免疫或细胞介导免疫反应产生的差异有关。我们的数据为在合理设计疫苗策略时考虑HPV16序列变异以及作为宫颈癌风险的流行病学关联提供了依据。
