Sören Hofmayer

Publications

• 3.76

  Impact points

  Unique sequence features of the Adenovirus 31 complete genomic sequence are conserved in clinical isolates.

  Soeren Hofmayer, Ijad Madisch, Sebastian Darr, Fabienne Rehren, Albert Heim

  BMC genomics. 11/2009; 10(1):557.

  ABSTRACT: BACKGROUND: Human adenoviruses (HAdV) are causing a broad spectrum of diseases. One of the most severe forms of adenovirus infection is a disseminated disease resulting in significant morbidity and mortality. Several reports in recent years have identified HAdV-31 from species A (HAdV-A31)... [more] ABSTRACT: BACKGROUND: Human adenoviruses (HAdV) are causing a broad spectrum of diseases. One of the most severe forms of adenovirus infection is a disseminated disease resulting in significant morbidity and mortality. Several reports in recent years have identified HAdV-31 from species A (HAdV-A31) as a cause of disseminated disease in children following haematopoetic stem cell transplantation (hSCT) and liver transplantation. We sequenced and analyzed the complete genome of the HAdV-A31 prototype strain to uncover unique sequence motifs associated with its high virulence. Moreover, we sequenced coding regions known to be essential for tropism and virulence (early transcription units E1A, E3, E4, the fiber knob and the penton base) of HAdV-A31 clinical isolates from patients with disseminated disease. RESULTS: The genome size of HAdV-A31 is 33763 base pairs (bp) in length with a GC content of 46.36%. Nucleotide alignment to the closely related HAdV-A12 revealed an overall homology of 84.2%. The genome organization into early, intermediate and late regions is similar to HAdV-A12. Sequence analysis of the prototype strain showed unique sequence features such as an immunoglobulin-like domain in the species A specific gene product E3 CR1 beta and a potentially integrin binding RGD motif in the C-terminal region of the protein IX. These features were conserved in all analyzed clinical isolates. Overall, amino acid sequences of clinical isolates were highly conserved compared to the prototype (99.2 to 100%), but a synonymous/non synonymous ratio (S/N) of 2.36 in E3 CR1-beta suggested positive selection. CONCLUSIONS: Unique sequence features of HAdV-A31 may enhance its ability to escape the host's immune surveillance and may facilitate a promiscuous tropism for various tissues. Moderate evolution of clinical isolates did not indicate the emergence of new HAdV-A31 subtypes in the recent years.

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• 3.26

  Impact points

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

  Sebastian Darr, Ijad Madisch, Sören Hofmayer, Fabienne Rehren, Albert Heim

  The Journal of general virology. 09/2009;

  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... [more] 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.

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• Unique sequence features of the Adenovirus 31 prototype complete genomic sequence are conserved in clinical isolates from cases of disseminated infection

  S. Hofmayer, I. Madisch, A. Heim

  60. DGHM, Dresden; 09/2008

• Unique sequence features of the Adenovirus 31 prototype complete genomic sequence are conserved in clinical isolates from cases of disseminated infection

  Sören Hofmayer, Ijad Madisch, Fabienne Rehren, Albert Heim

  01/2008
• 5.15

  Impact points

  Phylogenetic analysis and structural predictions of human adenovirus penton proteins as a basis for tissue-specific adenovirus vector design.

  Ijad Madisch, Soeren Hofmayer, Christian Moritz, Alexander Grintzalis, Jens Hainmueller, Patricia Pring-Akerblom, Albert Heim

  Journal of virology. 09/2007; 81(15):8270-81.

  The penton base is a major capsid protein of human adenoviruses (HAdV) which forms the vertices of the capsid and interacts with hexon and fiber protein. Two hypervariable loops of the penton are exposed on the capsid surface. Sequences of these and 300 adjacent amino acid residues of all 51 HAdV an... [more] The penton base is a major capsid protein of human adenoviruses (HAdV) which forms the vertices of the capsid and interacts with hexon and fiber protein. Two hypervariable loops of the penton are exposed on the capsid surface. Sequences of these and 300 adjacent amino acid residues of all 51 HAdV and closely related simian adenoviruses were studied. Adjacent sequences and predicted overall secondary structure were conserved. Phylogenetic analysis revealed clustering corresponding to the HAdV species and recombination events in the origin of HAdV prototypes. All HAdV except serotypes 40 and 41 of species F exhibited an integrin binding RGD motif in the second loop. The lengths of the loops (HVR1 and RGD loops) varied significantly between HAdV species with the longest RGD loop observed in species C and the longest HVR1 in species B. Long loops may permit the insertion of motifs that modify tissue tropism. Genetic analysis of HAdV prime strain p17'H30, a neutralization variant of HAdV-D17, indicated the significance of nonhexon neutralization epitopes for HAdV immune escape. Fourteen highly conserved motifs of the penton base were analyzed by site-directed mutagenesis of HAdV-D8 and tested for sustained induction of early cytopathic effects. Thus, three new motifs essential for penton base function were identified additionally to the RGD site, which interacts with a secondary cellular receptor responsible for internalization. Therefore, our penton primary structure data and secondary structure modeling in combination with the recently published fiber knob sequences may permit the rational design of tissue-specific adenoviral vectors.

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• Phylogenetic analysis and structural predictions of human adenovirus penton proteins: Basis for tissue specific adenoviral vector design.

  Madisch, Hofmayer, Moritz, Grintzalis, Akerblom, Heim A.

  Adenovirus: Basic research and application meeting, Ulm; 01/2007

• Molecular Phylogeny of the Penton Protein: Implications for the Molecular Evolution of Human Adenoviruses (HAdV).

  Madisch, Hofmayer, Harste, Pommer, Heim A.

  Annual Meeting GfV, Munich; 01/2006