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Journal of Virology, December 2005, p. 15265-15276, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15265-15276.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phylogenetic Analysis of the Main Neutralization and Hemagglutination Determinants of All Human Adenovirus Prototypes as a Basis for Molecular Classification and Taxonomy

Ijad Madisch, Gabi Harste, Heidi Pommer, and Albert Heim*

Institut für Virologie, Medizinische Hochschule Hannover, Hannover, Germany

Received 8 July 2005/ Accepted 29 September 2005

Human adenoviruses (HAdV) are responsible for a wide spectrum of diseases. The neutralization {varepsilon} determinant (loops 1 and 2) and the hemagglutination {gamma} determinant are relevant for the taxonomy of HAdV. Precise type identification of HAdV prototypes is crucial for detection of infection chains and epidemiology. {varepsilon} and {gamma} determinant sequences of all 51 HAdV were generated to propose molecular classification criteria. Phylogenetic analysis of {varepsilon} determinant sequences demonstrated sufficient genetic divergence for molecular classification, with the exception of HAdV-15 and HAdV-29, which also cannot be differentiated by classical cross-neutralization. Precise sequence divergence criteria for typing (<2.5% from loop 2 prototype sequence and <2.4% from loop 1 sequence) were deduced from phylogenetic analysis. These criteria may also facilitate identification of new HAdV prototypes. Fiber knob ({gamma} determinant) phylogeny indicated a two-step model of species evolution and multiple intraspecies recombination events in the origin of HAdV prototypes. HAdV-29 was identified as a recombination variant of HAdV-15 ({varepsilon} determinant) and a speculative, not-yet-isolated HAdV prototype ({gamma} determinant). Subanalysis of molecular evolution in hypervariable regions 1 to 6 of the {varepsilon} determinant indicated different selective pressures in subclusters of species HAdV-D. Additionally, {gamma} determinant phylogenetic analysis demonstrated that HAdV-8 did not cluster with -19 and -37 in spite of their having the same tissue tropism. The phylogeny of HAdV-E4 suggested origination by interspecies recombination between HAdV-B (hexon) and HAdV-C (fiber), as in simian adenovirus 25, indicating additional zoonotic transfer. In conclusion, molecular classification by systematic sequence analysis of immunogenic determinants yields new insights into HAdV phylogeny and evolution.

* Corresponding author. Mailing address: Institut für Virologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Phone: 49-511-5324311. Fax: 49-511-5325732. E-mail: Heim.Albert{at}mh-hannover.de.

Journal of Virology, December 2005, p. 15265-15276, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15265-15276.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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