Hermiston T W, Hellwig R, Hierholzer J C, Wold W S
Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, Missouri 63104.
Virology. 1993 Dec;197(2):593-600. doi: 10.1006/viro.1993.1633.
The adenovirus (Ad) early region 3 (E3) glycoprotein of 19K (gp19K) binds major histocompatibility (MHC) class I antigens in the endoplasmic reticulum (ER), and the gp19K-class I complex is retained in the ER through an ER retention signal at the C-terminus of gp19K. This retention of class I antigens blocks cytolysis of gp19K-expressing cells by cytotoxic T lymphocytes (CTL). Animal models infected with Ad mutants lacking gp19K support a role for gp19K in counteracting a CTL response. Gp19K binds with different avidities to different class I antigens, and portions of the gp19K sequence are highly variable among Ad serotypes in different subgroups (Ad3, 11, and Ad35 in subgroup B; Ad2 and Ad5 in subgroup C); this raises the possibility that certain human individuals may be more susceptible to productive or persistent infection by particular serotypes of Ad, depending on the haplotype of the individual and the type of Ad. To begin to address this possibility, the gp19K gene from 17 very diverse Ad7 (subgroup B) clinical isolates was amplified by the polymerase chain reaction, and the DNA sequences were determined. The Ad7 gp19K sequence was 98% identical to that of Ad3. Surprisingly, we found complete conservation of the amino acid sequence of gp19K from all but one of the clinical isolates; one isolate had a conservative Ala to Val substitution. Gp19K from Ad7 clinical isolates representing distinct Ad7 genotypes co-immunoprecipitated with class I antigens. Our data indicate that there is very strong evolutionary pressure to maintain the sequence of gp19K in Ad7. The only known function for gp19K from different Ad serotypes is binding to class I antigens. It is interesting to consider, therefore, what selective pressure operates to maintain the sequence of gp19K among serotypes within a subgroup, and yet allows for very significant divergence in the sequence of gp19K among serotypes in different subgroups. The possible role of MHC class I antigens in this selection process is discussed.
腺病毒（Ad）早期区域3（E3）的19K糖蛋白（gp19K）在内质网（ER）中与主要组织相容性（MHC）I类抗原结合，并且gp19K-I类复合物通过gp19K C末端的内质网滞留信号保留在内质网中。I类抗原的这种滞留阻止了细胞毒性T淋巴细胞（CTL）对表达gp19K的细胞的细胞溶解作用。感染缺乏gp19K的Ad突变体的动物模型支持gp19K在对抗CTL反应中的作用。Gp19K以不同的亲和力与不同的I类抗原结合，并且gp19K序列的部分在不同亚组的Ad血清型中高度可变（B亚组中的Ad3、11和Ad35；C亚组中的Ad2和Ad5）；这增加了一种可能性，即某些个体可能更容易受到特定血清型Ad的有效或持续感染，这取决于个体的单倍型和Ad的类型。为了开始探讨这种可能性，通过聚合酶链反应扩增了来自17种非常不同的Ad7（B亚组）临床分离株的gp19K基因，并测定了DNA序列。Ad7的gp19K序列与Ad3的序列有98%的同一性。令人惊讶的是，我们发现除了一个临床分离株外，所有临床分离株的gp19K氨基酸序列完全保守；一个分离株有一个保守的丙氨酸到缬氨酸的替换。代表不同Ad7基因型的Ad7临床分离株的gp19K与I类抗原共免疫沉淀。我们的数据表明，在Ad7中维持gp19K序列存在非常强的进化压力。来自不同Ad血清型的gp19K的唯一已知功能是与I类抗原结合。因此，有趣的是要考虑是什么选择压力在维持一个亚组内血清型之间的gp19K序列，而又允许不同亚组血清型之间的gp19K序列有非常显著的差异。本文讨论了MHC I类抗原在这一选择过程中的可能作用。
