Computational analysis of four human adenovirus type 4 genomes reveals molecular evolution through two interspecies recombination events

Abstract

Computational analysis of human adenovirus type 4 (HAdV-E4), a pathogen that is the only HAdV member of species E, provides insights into its zoonotic origin and molecular adaptation. Its genome encodes a domain of the major capsid protein, hexon, from HAdV-B16 recombined into the genome chassis of a simian adenovirus. Genomes of two recent field strains provide a clue to its adaptation to the new host: recombination of a NF-I binding site motif, which is required for efficient viral replication, from another HAdV genome. This motif is absent in the chimpanzee adenoviruses and the HAdV-E4 prototype, but is conserved amongst other HAdVs. This is the first report of an interspecies recombination event for HAdVs, and the first documentation of a lateral partial gene transfer from a chimpanzee AdV. The potential for such recombination events are important when considering chimpanzee adenoviruses as candidate gene delivery vectors for human patients.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…Similarly, HAdV-D67 was identified as a recombinant between HAdV-D9, -D25, -D26, -D33, and -D46 (46,55). Recent data provide evidence for the occurrence of recombination between different HAdV species, and even between HAdVs and SAdVs (56,57). Computational analysis of HAdV-E4, the only representative of species E, indicated that this virus is of zoonotic origin and evolved through two interspecies recombination events with lateral partial gene transfer.…”

“…Computational analysis of HAdV-E4, the only representative of species E, indicated that this virus is of zoonotic origin and evolved through two interspecies recombination events with lateral partial gene transfer. HAdV-E4 contains 97% of a SAdV-E26-like ge- nome chassis with a hexon containing the L1 and L2 regions from a HAdV-B16-like virus, which may provide compatibility with the new host (57). Adaptation of the virus to the new host could also be related to the acquirement of an NF-1 binding site motif, which is required for efficient viral replication, in a further recombination event.…”

Phylogenomic evidence for recombination of adenoviruses in wild gorillas

“…between members of different AdV species has also been reported, either between AdVs of the same primate host or of different primate hosts. Dehghan and coworkers showed that HAdV-4, the sole human member of species HAdV-E, originates from recombination of a domain of the hexon gene (encoding the major capsid protein) of HAdV-16 (species HAdV-B) into the genome of a member of species HAdV-E isolated from a captive chimpanzee (Dehghan et al, 2013b). Other examples of likely recombination between genomes of NHP AdVs and HAdVs are represented by SAdV-35.1 (from captive chimpanzee) and SAdV-35.2 (from captive bonobo) sharing high sequence similarity with HAdV-21 and HAdV-16 .…”

Homologous Recombination in E3 Genes of Human Adenovirus Species D

“…These viruses are nonenveloped with an icosahedral capsid and contain a linear, double-stranded DNA genome of 34 to 36 kb. The recent completion of whole-genome sequencing and analysis for all prototype HAdV genomes (6) has contributed to renewed understanding of the role of homologous recombination in the evolution of HAdVs, particularly species D, but also other HAdV species (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Genes for the three major capsid proteins, the hexon, penton base, and fiber, all readily recombine among viruses within HAdV-D (13,(17)(18)(19)(20)(21)(22)(23)(24)(25).…”