Emergence of a new human adenovirus type 4 (Ad4) genotype: Identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits

Ad4 is the principal etiological agent of acute respiratory disease (ARD) in the US military. Discovery of the novel 208 bp inverted terminal repeated (ITR) sequence from a recent Ad4 Jax78 field isolate was totally distinct from the analogous 116 bp ITR of Ad4 prototype. To investigate the origin and distribution of the novel Ad4 ITR sequence from ARD infections. Direct sequencing of ligated Ad ITR termini. The new Ad4 ITR was highly homologous with the ITRs of human Ad subgroup B. The left post-ITR region of Ad4 Jax78 was found to be highly homologous to the corresponding region of subgroup B Ads: 81% for Ad11 and 98% for Ad3 and Ad7. The right post-ITR region of Ad4 Jax78 contained a truncated classic ITR of the Ad4 prototype. The Ad4 Jax78 ITR most likely evolved from Ad4 prototype by substituting the Ad4 prototype ITR with the subgroup B Ads ITR. The ITR-based PCR assays developed from this study can be used to distinguish the new Ad4 genotype from the classical Ad4 prototype. The new Ad4 genotype was first detected in 1976 from Georgia, USA, and is the main causative agent of ARD infections in US military population.