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This Article Full Text (Papers in Press[PDF]) All Versions of this Article: vir.0.014514-0v1 90/12/2849    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Darr, S. Articles by Heim, A. PubMed PubMed Citation Articles by Darr, S. Articles by Heim, A. Agricola Articles by Darr, S. Articles by Heim, A.

Phylogeny and primary structure analysis of fiber shafts of all human adenovirus types for rational design of adenoviral gene therapy vectors

Institut für Virologie (Hannover)

¹ E-mail: heim.albert{at}mh-hannover.de

The fiber shaft of human adenoviruses (HAdV) is essential for bringing the penton base in proximity to the secondary cellular receptor. Fiber shaft sequences of all 53 HAdV types were studied. Phylogeny of the fiber shaft revealed clustering corresponding to the HAdV species concept. An intraspecies recombination hot spot was found at the shaft/knob boundary, a highly conserved sequence stretch. For example, HAdV-D20 clustered with -D23 in the fiber shaft but with HAdV-D47 in the fiber knob. Although all shafts exhibited the typical pseudorepeats, sequence divergence was found to be as high as 92% interspecies and 54% intraspecies. In contrast to a previous study, a flexibility motif (KXGGLXFD/N) was found in eight HAdV-D types whereas the putative heparan sulfate binding site (KKTK) was only found in species HAdV-C. Our results suggest that pseudotyping of gene therapy vectors at the shaft/knob-boundary is feasible but flexibility data of shafts should be considered.

Received 19 June 2009; accepted 4 August 2009.