Evidence of frequent recombination among human adenoviruses

• Published in: Journal of general virology 2008-02, Vol.89 (2), p.380-388
• Main Authors: Lukashev, Alexander N, Ivanova, Olga E, Eremeeva, Tatiana P, Iggo, Richard D
• Format: Article
• Language: English
• Subjects: Adenovirus; Adenovirus Infections, Human; Adenoviruses, Human - classification; Adenoviruses, Human - genetics; Capsid Proteins - genetics; DNA, Viral - genetics; Gene Order; Genes, Viral; Genetic Variation; Genome, Viral; Humans; Molecular Sequence Data; Phylogeny; Recombination, Genetic; Viral Proteins - genetics
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.83057-0

1 Bute Medical School, University of St Andrews, Scotland, UK 2 Institute of Poliomyelitis and Viral Encephalitides RAMS, Moscow, Russia Correspondence Alexander N. Lukashev alexander_lukashev{at}hotmail.com Genome stability is a prerequisite for the production and use of adenoviruses for therapy of genetic diseases and cancer. To test the premise that the adenoviral genome is stable, the phylogenetic relationships of 16 adenovirus C (AdC) field isolates were studied in four genome regions: hexon, fiber, polymerase and E1A. The phylogenetic relationships in the fiber gene concurred with those in the hexon region. In contrast, the non-structural regions had marks of frequent recombination, to the point that an isolate of one serotype could contain non-structural proteins that were identical to the genes from a different serotype. Our results suggest that recombination among circulating adenoviruses is very frequent and plays an important role in shaping the phylogenetic relationships of adenovirus genomes. Analysis of the available complete genome sequences of AdB, AdC and AdD species showed that recombination shuffles genome fragments within a species, but not between species. One of the AdC field isolates possessed the fiber gene of AdC type 6, but a hexon gene that was distinct from all AdC serotypes. This strain could not be typed unambiguously in a neutralization test and might represent a novel serotype of AdC. Comparison of the right end (nt 18838–33452) of this isolate with that of the ATCC Ad6 strain showed clear evidence of multiple recombination events. The GenBank/EMBL/DDBJ accession numbers for the sequences determined in this study are EU192298–EU192361. A supplementary table showing oligonucleotides used to amplify AdC genome fragments is available with the online version of this paper.