GENETIC ORGANIZATION, SIZE, AND COMPLETE SEQUENCE OF EARLY REGION-3 GENES OF HUMAN ADENOVIRUS TYPE-41

The complete nucleotide and predicted amino acid sequences for open re ading frames (ORFs) of the human adenovirus type 41 (Ad41) early regio n 3 (E3) gene have been determined. The sequence of the Ad41 E3 gene ( map units 74 to 83.9) consists of 3,373 nucleotides and has one TATA b ox and two polyadenylation signals (AATAAA). Analysis of the nucleotid e sequence reveals that the E3 gene can encode six ORFs, designated RL 1 to RL6. These are all expressed at the mRNA level, as determined by reverse transcription-PCR analysis of Ad41-infected cell RNA. When com pared with known E3 sequences of most other human adenoviruses deposit ed in GenBank, the sequences of RL1 to RL3 were found to be unique to subgroup F adenoviruses (Ad40 and Ad41). They encode putative proteins of 173 amino acids (19.4 kDa) and 276 amino acids (31.6 kDa) in one r eading frame as well as a 59-amino-acid (6.7 kDa) protein in an overla pping reading frame. RL4 encodes a 90-amino-acid protein (10.1 kDa) wi th 40% homology to the Ad2 E3 10.4-kDa protein, which induces degradat ion of the epidermal growth factor receptor and functions together wit h the Ad2 E3 14.5-kDa protein to protect mouse cell lines against lysi s. RL5 encodes a protein of 107 amino acid residues (12.3 kDa) and is analogous to the Ad2 E3 14.5-kDa protein. RL6 codes for a protein of 1 22 amino acids (14.7 kDa) that is analogous to the Ad2 14.7-kDa protei n, which functions to protect Ad-infected cells from tumor necrosis fa ctor-induced cytolysis. This finding of three unique (RL1 to RL3) E3 g ene ORFs may explain why subgroup F adenoviruses differ substantially from other human adenoviruses in their host range; i.e., they replicat e predominantly in the host's gastrointestinal rather than respiratory tract. A recent phylogenetic study that compared subgroup F Ad40 DNA sequences with representatives of subgroups B (Ad3), C (Ad2), and E (A d4) reached a similar conclusion about the uniqueness of RL1 and RL2.