Sequence and functional analysis of the human adenovirus type 7 E3-gp19K protein from 17 clinical isolates

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.