title: The novel early region 3 protein E3/49K is specifically expressed by adenoviruses of subgenus D: implications for epidemic keratoconjunctivitis and adenovirus evolution.
abstract: The early transcription unit 3 (E3) of adenoviruses (Ads) encodes immunomodulatory functions. We previously described a novel gene of 49K within the E3 region of Ad19a, an Ad of subgenus D that is similar to Ad8 and Ad37 causes epidemic keratoconjunctivitis (EKC). Interestingly, 49K was reported not to be present in Ad9 and Ad17, other subgenus D Ads not causing EKC. Therefore, we investigated whether 49K is selectively expressed in EKC-causing Ads. Using specific DNA probes, we detect 49K-homologous genes in all subgenus D Ads tested. Moreover, 49K-specific antibodies recognize a high molecular weight protein in cells infected with all subgenus D serotypes irrespective of their ability to cause EKC. Sequencing of several 49K genes reveals a high homology without a distinct feature recognizable for those of EKC-associated Ad strains. Thus, E3/49K is a subgenus D specific E3 protein whose expression does not correlate with the EKC-causing phenotype and thus may rather be implicated in illnesses commonly caused by this subgenus. Interestingly, the 49K sequences of Ad19a and Ad37 are identical. To estimate the extent of the sequence identity between these two viruses, we initially sequenced the right ITR and the hexon. This analysis revealed that the right ITR of Ad19a is identical to Ad37, while the hexon sequence is Ad19p-like. This suggested that the region of identity is much larger and that Ad19a arose by recombination of Ad37 with an Ad19p-like Ad. Further sequencing mapped the crossover within the DNA binding protein. Thus, Ad19a contains a large sequence block ( approximately 13 kb), from the 100K gene to the right ITR, identical to Ad37. The implications of these findings in light of the temporal appearance of the EKC-causing Ad strains are discussed.
authors.affiliation: Max-von-Pettenkofer Institute, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jürgen H
authors.initials: JH
authors.lastname: Blusch
authors.forename: François
authors.initials: F
authors.lastname: Deryckere
authors.forename: Mark
authors.initials: M
authors.lastname: Windheim
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ruzsics
authors.forename: Niklas
authors.initials: N
authors.lastname: Arnberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Adrian
authors.forename: Hans-Gerhard
authors.initials: HG
authors.lastname: Burgert
mesh_terms: D017503:Adenovirus E3 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000258:Adenovirus Infections, Human / Q000821:virology; D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D000595:Amino Acid Sequence; D001483:Base Sequence; D002213:Capsid; D036022:Capsid Proteins; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D019143:Evolution, Molecular; D006801:Humans; D007637:Keratoconjunctivitis / Q000821:virology; D008168:Lung; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011995:Recombination, Genetic; D016415:Sequence Alignment; D020079:Terminal Repeat Sequences
chemical_list: D017503:Adenovirus E3 Proteins; D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus