Molecular Evolution of Human Adenovirus (HAdV) Species C

Abstract

Currently, 88 different Human Adenovirus (HAdV) types are grouped into seven HAdV species A to G. Most types (57) belong to species HAdV-D. Recombination between capsid genes (hexon, penton and fiber) is the main factor contributing to the diversity in species HAdV-D. Noteworthy, species HAdV-C contains so far only five types, although species HAdV-C is highly prevalent and clinically significant in immunosuppressed patients. Therefore, the evolution of species HAdV-C was studied by generating 51 complete genome sequences from circulating strains. Clustering of the whole genome HAdV-C sequences confirmed classical typing results (fifteen HAdV-C1, thirty HAdV-C2, four HAdV-C5, two HAdV-C6). However, two HAdV-C2 strains had a novel penton base sequence and thus were re-labeled as the novel type HAdV-C89. Fiber and early gene region 3 (E3) sequences clustered always with the corresponding prototype sequence but clustering of the E4 region indicated recombination events in 26 out of the 51 sequenced specimens. Recombination of the E1 gene region was detected in 16 circulating strains. As early gene region sequences are not considered in the type definition of HAdVs, evolution of HAdV-C remains on the subtype level. Nonetheless, recombination of the E1 and E4 gene regions may influence the virulence of HAdV-C strains.

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“…Nevertheless, recombination does not seem to appear to be restricted to these regions. For HAdV-C, no recombination could be detected for the minor capsid proteins (IIIa, V-IX), yet all early ( E ) gene regions demonstrated multiple recombination events [ 25 ]. More importantly, these regions could be exchanged independent of one another, regardless of their intergenic relations.…”

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“…The first alternative Ad types used as vectors were derived from the species C Ads. Species C adenoviruses include Ad types 1, 2, and 6 and the more recently discovered Ad type 57 . However, until today HAdV‐C5 vectors were applied in the vast majority of investigations and only limited studies were performed utilizing Ad types 1, 2, and 6.…”