Adenovirus research group Current projects dealing with the adenovirus External links for students and researchers Research and published papers
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Adenovirus research group

Since 1988 a research group on adenoviruses is located at the Institute of Virology. This research group was closely linked to the German resource center for adenoviruses. Head of both units was Dr. Adrian, and later Dr. Pring-Åkerblom until the year 2000. Development of genotyping techniques by restriction fragment polymorphism and PCR methods for genus-, species- and type-specific PCR protocols were the first main goals. Research projects included studies on capsid structures of adenoviruses including elaborate sequencing studies on receptor binding sites and hemagglutination domains. Newer studies include the molecular phylogeny of the neutralization determinant (epsilon) and the hemagglutination determinant (gamma), as a basis for molecular classification and taxonomy for human adenoviruses. Results of this extensive project on molecular phylogeny indicated that all human adenoviruses can be unequivocally typed by simple sequencing of loop 2 of the neutralization determinant epsilon. Moreover, results demonstrated the significance of recombination events in the evolution of humen adenovirus types. Another project elucidated also the phylogeny of the penton base protein which binds to the secondary cellular receptor. Results of this study can be applied to the design of tissue specific gene therapy vectors. Another research focus is the pathogenesis of relevant diseases caused by adenoviruses, for example disseminated disease of the immunosuppressed patient and epidemic keratoconjunctivitis Projects focused on the virus load kinetics of disseminated adenovirus infections, including development of a quantitative PCR assay for adenoviruses. Furthermore, concentrations of adenovirus DNA in different organs and tissues were studied and correlated with symptoms. Molecular characterization of human adenovirus type 31 which caused several fatal infections in immunosuppressed patients is another research topic.



Staff

PD Dr. med. Albert Heim
    +49 (0)511 532 4311 | Heim.Albert@MH-Hannover.De

Gabriele Harste, MTA
    +49 (0)511 532 4327 | Harste.Gabriele@MH-Hannover.De

Sebastian Darr, Doktorand

    +49 (0)511 532 4327 | Darr.Sebastian@MH-Hannover.De

Rüdiger Stock, Doctoral candidate

Ijad Madisch, Doctoral candidate

    +49 (0)511 532 4311 | Madisch.Ijad@MH-Hannover.De

Sören Hofmayer, Doctoral candidate

    +49 (0)511 532 4311 | Hofmayer.Soeren@MH-Hannover.De

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Current research, project information and links

Project information

Phylogenetic Analysis and Structural Predictions of Human Adenovirus Penton Proteins as a Basis for Tissue-Specific Adenovirus Vector Design

Project summary:
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.

Project scientists:
  Ijad Madisch Sören Hofmayer
  Albert Heim

An Outbreak of Epidemic Keratoconjunctivitis Caused by a New Intermediate Adenovirus 22/H8 Identified by Molecular Typing

Project summary:
TIn a 4-week period, 12 patients contracted adenoviral keratoconjunctivitis. Eight of these patients had visited the same ophthalmologist's practice before onset of symptoms. Adenovirus was detected in swab specimens obtained from 9 patients. Sequence-based typing of 2 isolates revealed type 22/H8. This is, to our knowledge, the first report of a keratoconjunctivitis outbreak caused by an intermediate adenovirus type 22/H8. Moreover, the outbreak virus had a type 37 like sequence of the penton base. Therfore, a double reombination event between type 22 (neutralization properties), type 8 (hemaaglutination properties and binding of primary cellular receptor) and type 37 (binding site for secondary cellular receptor) must be considered in the phylogeny of this unusual keratokonjunctivitis type.

Project scientists:
  Ilka Engelmann Ijad Madisch
  Albert Heim

Development of a quantitative PCR for the diagnosis of disseminated adenovirus infections

Project summary:
Rapid diagnosis of human adenovirus (HAdV) infections was achieved by PCR in the recent years. However, conventional PCR has the risk of carry-over contamination due to open handling with its products, and results are only qualitative. Therefore, a quantitative "real-time" PCR with consensus primer and probe (dual fluorescence labeled, "TaqMan") sequences for a conserved region of the hexon gene was designed and evaluated. Real-time PCR detected all 51 HAdV prototypes. Sensitivity of the assay was smaller than 15 copies/run and the linear range of quantitation 1.5 x 10e1 to 1.5 x 10e8 copies/run. TaqMan PCR gave identical results compared to an established conventional one step PCR protocol in 218 (38 positive, 180 negative) of 234 clinical samples including blood, serum, eye swabs and faeces, and had divergent results in 16 samples (15 positive only in TaqMan PCR, all with low copy numbers, 1 positive in only conventional PCR) indicating a higher sensitivity of TaqMan PCR. Adenovirus viremia was detected by TaqMan PCR in 4 of 27 (14.8%) paediatric and 8 of 93 (8.6%) adult stem cell transplant recipients but only in 5 of 306 healthy controls (blood donors, 1.6%). Virus loads of pediatric patients (median 1.7 x 10e5) were significantly higher than in adult patients (median 2.3 x 10e3) and than in controls (all samples smaller than 1.7 x10e3 copies/ml). A few immunosuppressed children had very high virus loads (up to 1.1 x 10e10 copies/ml) which were associated with symptoms of disseminated disease. In conclusion, real-time PCR is a sensitive and quantitative procedure for the detection of adenovirus infections.

Project scientists:
  Carmen Ebnet Gabriele Harste
  Patricia Pring-Åkerblom Albert Heim
Testing of anti-adenoviral agents with help of DNA replication kinetics

Project summary:
Testing the anti-adenovirus activity of antiviral agents is not an easy task. In cell cultures, visual inspection of CPE is error prone. Therefore, CPE based antiviral activity data has high variabilities. Moreover, no real animal models exist which provides multiple rounds of virus replication for testing antiviral agents. Therefore, we are developing an assay for rapid testing of antiviral agents measuring the intracellular increase of adenovirus DNA during first round of virus replication. This assay is used for in vitro (cell culture) studies on antiviral agents but may be also used for first round of replication animal models.

Project scientists:
  Rüdiger Stock Gabriele Harste
  Albert Heim

Phylogenetic Analysis of Main Neutralization (epsilon) and Hemagglutination (gamma) Determinants of all Human Adenovirus Prototypes as a Basis for Molecular Classification and Taxonomy

Project summary:
Human adenoviruses (HAdV) are responsible for a wide spectrum of diseases. The neutralization ?determinant (epsilon, 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. Epsilon and gamma determinant sequences of all 51 HAdV were generated to propose molecular classification criteria. Phylogenetic analysis of epsilon ?determinant sequences demonstrated sufficient genetic divergence for molecular classification, with exception of HAdV-15 and HAdV-29, which also cannot be differentiated by classical cross-neutralization. Precise sequence divergence criteria for typing (smaller than 2.5% to loop 2 prototype sequence, smaller than 2.4 % loop 1) 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 (epsilon determinant) and a speculative, not yet isolated HAdV prototype (gamma determinant). Subanalysis of molecular evolution in hypervariable regions 1 - 6 of the epsilon 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 the same tissue tropism. Phylogeny of HAdV-E4 suggested origin 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 in HAdV phylogeny and evolution.

Project scientists:
  Ijad Madisch Gabriele Harste
  Albert Heim Heidi Pommer

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Software PNCH

PNCH - pairwise nucleotide comparison histogram maker- freeware von I. Madisch. Dieses Programm erstellt Histogramme aus Matrix (Sequenz-Identität) Dateien mit der Option diese als Grafik Datei zu exportieren. Das Programm ist ein "p file" des MatLab Softwarepakets und erfordert zur Ausführung eine lizensierte MatLab Installation. Die zu importierende Matrix Datei muß im Excel (*.xls) oder als Komma getrennte Tabelle (*.csv) vorliegen.

Software download

Molecular Identification of Adenovirus Sequences: a Rapid Scheme for Early Typing of Human Adenoviruses in Diagnostic Samples of Immunocompetent and Immunodeficient Patients

Project summery:
Precise typing of human adenoviruses (HAdV) is fundamental for epidemiology and the detection of infection chains. As only few of the 51 adenovirus types are associated with life threatening disseminated diseases in immunodeficient patients, detection of one of these types may have prognostic value and lead to immediate therapeutic intervention. A recently published molecular typing scheme consisting of two steps (sequencing of a generic PCR product closely adjacent to loop1 of the main neutralization determinant e, and for species HAdV-B, -C and -D the sequencing of loop 2) was applied to 119 clinical samples. HAdV DNA was typed unequivocally even in cases of culture negative samples, for example in immunodeficient patients before HAdV causes high virus loads and disseminated disease. Direct typing results demonstrated the predominance of HAdV-1, -2, -5 and -31 in immunodeficient patients suggesting the significance of the persistence of these viruses for the pathogenesis of disseminated disease. In contrast, HAdV-3 predominated in immunocompetent patients and cocirculation of four subtypes was demonstrated. Typing of samples from a conjunctivitis outbreak in multiple military barracks demonstrated various HAdV types (2, 4, 8, 19) and not the suspected unique adenovirus etiology. This suggests that our molecular typing scheme will be also useful for epidemiological investigations. In conclusion, our two step molecular typing system will permit the precise and rapid typing of clinical HAdV isolates and even of HAdV DNA in clinical samples without the need of time consuming virus isolation prior to typing.

Project scientists:
  Ijad Madisch Gabriele Harste
  Albert Heim Heidi Pommer



For simplifying molecular typing you can download the following databases which only contain relevant human adenovirus sequences.

Protein typing database local blast (zip)

Nucleotide typing database local blast (zip)


Based on this database an online adenovirus local Blast search with the relevant adenovirus sequences for typing is provided by Professor Balazs Harrach and Dr. Peter Elo (Veterinary Medical Research Institute, Hungarian Academy of Sciences). This website permits rapid and simple typing results after submitting hexon loop2 or hexon 5´end (generic PCR) sequences

Direct Blast Server for Molecular Typing of Adenoviruses (Two step concept including L2-Sequences)



External resources

For short descriptions of adenoviruses:
www.virology.net/garryfavweb11.html
www.uct.ac.za/depts/mmi/stannard/adeno.html
www.stanford.edu/group/virus/adeno/adeno.html
www.fda.gov/ohrms/dockets/ac/01/slides/3868s1_05_flomenberg/sld024.htm

More detailed descriptions of adenoviruses for students and scientists:

www.vu-wien.ac.at/i123/SPEZVIR/ADENOGEN1.HTML

ICTV taxonomic information
www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/01000000.htm

Lots of data and links
www.nlv.ch/Adenovirus/Adenofactsheet.htm A review about adenovirus vectors in gene therapy:
www.socgenmicrobiol.org.uk/JGVDirect/17217/17217ft.htm A special blast service for adenovirus sequences:
www.vmri.hu/blast.htm A visual sequence database:
www.vmri.hu/~harrach/adenoseq.htm A general taxonomy based sequence browser:
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy


For scientists:

A review about adenovirus vectors in gene therapy:
www.socgenmicrobiol.org.uk/JGVDirect/17217/17217ft.htm

A special blast service for adenovirus sequences:
www.vmri.hu/blast.htm

A visual sequence database:
www.vmri.hu/~harrach/ADENOSEQ.HTM

A general taxonomy based sequence browser:
www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

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Published papers

Madisch I, Heim A (2007) Extent of circulation of incorrectly labeled adenovirus 50 and 51 prototype preparations. J Clin Microbiol 45:2092


Madisch I, Hofmayer S, Moritz C, Grintzalis A, Hainmueller J, Pring-Akerblom P, Heim A (2007) Phylogenetic analysis and structural predictions of human adenovirus penton proteins as a basis for tissue-specific adenovirus vector design. J Virol 81:8270-81.


Hoffmann D, Heim A, Nettelbeck DM, Steinstraesser L, Wildner O. (2007) Evaluation of Twenty Human Adenoviral Types and One Infectivity-Enhanced Adenovirus for the Therapy of Soft Tissue Sarcoma. Hum Gene Ther. 2006 Dec 18: 51-62.


Engelmann I, Madisch I, Pommer H, Heim A. (2006) An outbreak of epidemic keratoconjunctivitis caused by a new intermediate adenovirus 22/H8 identified by molecular typing. Clin Infect Dis. 43:e64-6.


Stock R, Harste G, Madisch I, Heim A. (2006) A rapid quantitative PCR-based assay for testing antiviral agents against human adenoviruses demonstrates type specific differences in ribavirin activity. Antiviral Res. 72:34-41.


Madisch I, Wolfel R, Harste G, Pommer H, Heim A (2006) Molecular identification of adenovirus sequences: A rapid scheme for early typing of human adenoviruses in diagnostic samples of immunocompetent and immunodeficient patients. J Med Virol. 78, 1210-17.


Madisch I., Harste G., Pommer H., Heim A. " Phylogenetic Analysis of Main Neutralization (e) and Hemagglutination (g) Determinants of all Human Adenovirus Prototypes as a Basis for Molecular Classification and Taxonomy" J. Virol, 79, 15265-76.


van Heerden J., Ehlers MM, Heim A., Grabow WOK. "Prevalence, quantification and typing of adenoviruses detected in river and treated drinking water in South Africa." J Appl. Microbiol. 2005, 99: 234-242.


Seidemann K., Heim A., Pfister E., Koditz H., Beilken A., Sander A., Melter M., Sykora KW, Sasse M., Wessel A. "Monitoring of adenovirus infection in pediatric transplant recipients by quantitative PCR." Am J Transplant, 2004, 4(12): 2102-8.


Sauerbrei A., Sehr K., Brandstadt A., Heim A., Reimer K., Wutzler P. "Sensitivity of human adenoviruses to different groups of chemical biocides." J Hosp Infect, 2004, 57: 59-66.


Friedrichs N., Eis-Hubinger AM., Heim A., Platen E., Zhou H., Buettner R. "Acute adenoviral infection of a graft by serotype 35 following renal transplantation." Pathol Res Pract, 2003; 199: 565-570.


Heim A., Ebnet C., Harste G., Pring-Åkerblom P. "Rapid and Quantitative Detection of Human Aenovirus DNA by Real-Time PCR." J Med Virology, 2003 70:228-239.


Arnberg N., Kidd AH, Edlund K., Nilsson J., Pring-Åkerblom P., Wadell G. "Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction." Virology. 2002 Oct 10;302(1):33-43.


Arnberg N., Pring-Åkerblom P., Wadell G. "Adenovirus type 37 uses sialic acid as a cellular receptor on Chang C cells." J Virol. 2002 Sep;76(1 7):8834-41.


Blusch JH, Deryckere F., Windheim M., Ruzsics Z., Arnberg N., Adrian T., Burgert HG. "The novel early region 3 protein E3/49K is specifically expressed by adenoviruses of subgenus D: implications for epidemic keratoconjunctivitis and adenovirus evolution." Virology. 2002 Apr 25;296(1):94-106.


Cichon G., Boeckh-Herwig S., Schmidt HH., Wehnes E., Muller T., Pring-Åkerblom P., Burger R. "Complement activation by recombinant adenoviruses." Gene Ther. 2001 Dec;8(23):1794-800.


Pring-Åkerblom P., Trijssenaar FE., Adrian T., Hoyer H. "Multiplex polymerase chain reaction for subgenus-specific detection of human adenoviruses in clinical samples." J Med Virol. 1999 May;58(1):87-92.


Grumbach IM, Heim A., Pring-Åkerblom P., Vonhof S., Hein WJ, Muller G., Figulla HR. "Adenoviruses and enteroviruses as pathogens in myocarditis and dilated cardiomyopathy." Acta Cardiol. 1999 Apr;54(2):83-8.


Liebermann H., Mentel R., Bauer U., Pring-Åkerblom P., Dolling R., Modrow S., Seidel W. ."Receptor binding sites and antigenic epitopes on the fiber knob of human adenovirus serotype 3." J Virol. 1998 Nov;72(11):9121-30.


Pring-Åkerblom P., Heim A., Trijssenaar FE. "Molecular characterization of hemagglutination domains on the fibers of subgenus D adenoviruses." J Virol. 1998 Mar;72(3):2297-304.


Eiz B., Pring-Åkerblom P. "Molecular characterization of the type-specific gamma-determinant located on the adenovirus fiber." J Virol. 1997 Sep;71(9):6576-81.


Pring-Åkerblom P., Blazek K., Schramlova J., Kunstyr I. "Polymerase chain reaction for detection of guinea pig adenovirus." J Vet Diagn Invest. 1997 Jul;9(3):232-6.


Pring-Åkerblom P., Adrian T., Kostler T. "PCR-based detection and typing of human adenoviruses in clinical samples." Res Virol. 1997 May-Jun;148(3):225-31.


Pring-Åkerblom P., Heim A., Trijssenaar FE. "Conserved sequences in the fibers of epidemic keratoconjunctivitis associated human adenoviruses." Arch Virol. 1997;142(1):205-11.


Eiz B., Adrian T., Pring-Åkerblom P. "Recombinant fibre proteins of human adenoviruses Ad9, Ad15 and Ad19: localization of the haemagglutination properties and the type-specific determinant." Res Virol. 1997 Jan-Feb;148(1):5-10.


Adrian T. "Genome polymorphism of human adenoviruses of subgenus C." Arch Virol. 1996;141(6):1021-31.


Eiz B., Adrian T., Pring-Åkerblom P. "Immunological adenovirus variant strains of subgenus D: comparison of the hexon and fiber sequences." Virology. 1995 Nov 10;213(2):313-20.


Pring-Åkerblom P., Trijssenaar FE., Adrian T.. "Hexon sequence of adenovirus type 7 and comparison with other serotypes of subgenus B." Res Virol. 1995 Nov-Dec;146(6):383-388.


Pring-Åkerblom P., Trijssenaar FE., Adrian T. "Sequence characterization and comparison of human adenovirus subgenus B and E hexons." Virology. 1995 Sep 10;212(1):232-6.


Pring-Åkerblom P., Adrian T. "Sequence characterization of the adenovirus 31 fibre and comparison with serotypes of subgenera A to F." Res Virol. 1995 Sep-Oct;146(5):343-54.


Pring-Åkerblom P., Adrian T. "Characterization of adenovirus subgenus D fiber genes." Virology. 1995 Jan 10;206(1):564-71.


Pring-Åkerblom P., Adrian T. "Type- and group-specific polymerase chain reaction for adenovirus detection." Res Virol. 1994 Jan-Feb;145(1):25-35.


Pring-Åkerblom P., Adrian T. "The hexon genes of adenoviruses of subgenus C: comparison of the variable regions." Res Virol. 1993 Mar-Apr;144(2):117-27.


Adrian T., Brunnemann H., Wigand R. "Adenovirus isolations from patients with conjunctivitis in Thuringia." Zentralbl Bakteriol. 1993 Feb;278(1):127-31.


Adrian T. "Genome type analysis of adenovirus type 4." Intervirology. 1992;34(4):180-3.


Adrian T., Wigand R. "Restriction site mapping of subgenus D adenoviruses, prototypes 42-47, intermediate and atypical strains." Zentralbl Bakteriol. 1991 Dec;276(1):107-19.


Wigand R., Adrian T. "A rational system for classifying and denominating adenovirus genome types." Res Virol. 1991 Jan-Feb;142(1):47-56.


Adrian T., Wolf U., Lauer HJ., Wigand R. "Restriction site mapping of adenovirus type 8 genome types." Res Virol. 1990 Nov-Dec;141(6):611-24.


Adrian T., Sassinek J., Wigand R. "Genome type analysis of 480 isolates of adenovirus types 1, 2, and 5." Arch Virol. 1990;112(3-4):235-48.


Wigand R., Adrian T. "Restriction site mapping of adenovirus prototypes of subgenus D." Med Microbiol Immunol (Berl). 1990;179(2):67-75.


Adrian T., Wolf U. "Adenovirus 6 genome types: mapping of restriction site alterations on the genome." Res Virol. 1989 Nov-Dec;140(6):545-50.


Adrian T., Schlipkoter U., Roggendorf M., Wigand R. "Nosocomial and endemic infections with a genome type of adenovirus type 5." Zentralbl Bakteriol. 1989 Sep;271(3):339-44. PMID: 2553041 [PubMed - indexed for MEDLINE]


Adrian T, Best B, Hierholzer JC, Wigand R. "Molecular epidemiology and restriction site mapping of adenovirus type 3 genome types." J Clin Microbiol. 1989 Jun;27(6):1329-34.


Adrian T., Wigand R. "Genome type analysis of certain adenovirus serotypes of subgenus D." Zentralbl Bakteriol Mikrobiol Hyg [A]. 1989 Mar;270(4):527-33.


Adrian T., Wigand R., Knocke KW., Schafer G., Grundmann M. "Genome type analysis of adenoviruses: isolates from one year from the Hannover area." Arch Virol. 1989;105(1-2):89-101.


Adrian T., Becker M., Hierholzer JC., Wigand R. "Molecular epidemiology and restriction site mapping of adenovirus 7 genome types." Arch Virol. 1989;106(1-2):73-84.


Adrian T., Bastian B., Wagner V. "Restriction site mapping of adenovirus types 9 and 15 and genome types of intermediate adenovirus. "15/H9. Intervirology. 1989;30(3):169-76.


Wigand R, Adrian T. "Intermediate adenovirus strains of subgenus D occur in extensive variety." Med Microbiol Immunol (Berl). 1989;178(1):37-44.

Friedrichs N., Eis-Hubinger AM., Heim A., Platen E., Zhou H., Buettner R. "Acute adenoviral infection of a graft by serotype 35 following renal transplantation." Pathol Res Pract, 2003; 199: 565-570.


Heim A., Ebnet C., Harste G., Pring-Åkerblom P. "Rapid and Quantitative Detection of Human Aenovirus DNA by Real-Time PCR." J Med Virology, 2003 70:228-239.


Arnberg N., Kidd AH, Edlund K., Nilsson J., Pring-Åkerblom P., Wadell G. "Adenovirus type 37 binds to cell surface sialic acid through a charge-dependent interaction." Virology. 2002 Oct 10;302(1):33-43.


Arnberg N., Pring-Åkerblom P., Wadell G. "Adenovirus type 37 uses sialic acid as a cellular receptor on Chang C cells." J Virol. 2002 Sep;76(1 7):8834-41.


Blusch JH, Deryckere F., Windheim M., Ruzsics Z., Arnberg N., Adrian T., Burgert HG. "The novel early region 3 protein E3/49K is specifically expressed by adenoviruses of subgenus D: implications for epidemic keratoconjunctivitis and adenovirus evolution." Virology. 2002 Apr 25;296(1):94-106.


Cichon G., Boeckh-Herwig S., Schmidt HH., Wehnes E., Muller T., Pring-Åkerblom P., Burger R. "Complement activation by recombinant adenoviruses." Gene Ther. 2001 Dec;8(23):1794-800.


Pring-Åkerblom P., Trijssenaar FE., Adrian T., Hoyer H. "Multiplex polymerase chain reaction for subgenus-specific detection of human adenoviruses in clinical samples." J Med Virol. 1999 May;58(1):87-92.


Grumbach IM, Heim A., Pring-Åkerblom P., Vonhof S., Hein WJ, Muller G., Figulla HR. "Adenoviruses and enteroviruses as pathogens in myocarditis and dilated cardiomyopathy." Acta Cardiol. 1999 Apr;54(2):83-8.


Liebermann H., Mentel R., Bauer U., Pring-Åkerblom P., Dolling R., Modrow S., Seidel W. ."Receptor binding sites and antigenic epitopes on the fiber knob of human adenovirus serotype 3." J Virol. 1998 Nov;72(11):9121-30.


Pring-Åkerblom P., Heim A., Trijssenaar FE. "Molecular characterization of hemagglutination domains on the fibers of subgenus D adenoviruses." J Virol. 1998 Mar;72(3):2297-304.


Eiz B., Pring-Åkerblom P. "Molecular characterization of the type-specific gamma-determinant located on the adenovirus fiber." J Virol. 1997 Sep;71(9):6576-81.


Pring-Åkerblom P., Blazek K., Schramlova J., Kunstyr I. "Polymerase chain reaction for detection of guinea pig adenovirus." J Vet Diagn Invest. 1997 Jul;9(3):232-6.


Pring-Åkerblom P., Adrian T., Kostler T. "PCR-based detection and typing of human adenoviruses in clinical samples." Res Virol. 1997 May-Jun;148(3):225-31.


Pring-Åkerblom P., Heim A., Trijssenaar FE. "Conserved sequences in the fibers of epidemic keratoconjunctivitis associated human adenoviruses." Arch Virol. 1997;142(1):205-11.


Eiz B., Adrian T., Pring-Åkerblom P. "Recombinant fibre proteins of human adenoviruses Ad9, Ad15 and Ad19: localization of the haemagglutination properties and the type-specific determinant." Res Virol. 1997 Jan-Feb;148(1):5-10.


Adrian T. "Genome polymorphism of human adenoviruses of subgenus C." Arch Virol. 1996;141(6):1021-31.


Eiz B., Adrian T., Pring-Åkerblom P. "Immunological adenovirus variant strains of subgenus D: comparison of the hexon and fiber sequences." Virology. 1995 Nov 10;213(2):313-20.


Pring-Åkerblom P., Trijssenaar FE., Adrian T.. "Hexon sequence of adenovirus type 7 and comparison with other serotypes of subgenus B." Res Virol. 1995 Nov-Dec;146(6):383-388.


Pring-Åkerblom P., Trijssenaar FE., Adrian T. "Sequence characterization and comparison of human adenovirus subgenus B and E hexons." Virology. 1995 Sep 10;212(1):232-6.


Pring-Åkerblom P., Adrian T. "Sequence characterization of the adenovirus 31 fibre and comparison with serotypes of subgenera A to F." Res Virol. 1995 Sep-Oct;146(5):343-54.


Pring-Åkerblom P., Adrian T. "Characterization of adenovirus subgenus D fiber genes." Virology. 1995 Jan 10;206(1):564-71.


Pring-Åkerblom P., Adrian T. "Type- and group-specific polymerase chain reaction for adenovirus detection." Res Virol. 1994 Jan-Feb;145(1):25-35.


Pring-Åkerblom P., Adrian T. "The hexon genes of adenoviruses of subgenus C: comparison of the variable regions." Res Virol. 1993 Mar-Apr;144(2):117-27.


Adrian T., Brunnemann H., Wigand R. "Adenovirus isolations from patients with conjunctivitis in Thuringia." Zentralbl Bakteriol. 1993 Feb;278(1):127-31.


Adrian T. "Genome type analysis of adenovirus type 4." Intervirology. 1992;34(4):180-3.


Adrian T., Wigand R. "Restriction site mapping of subgenus D adenoviruses, prototypes 42-47, intermediate and atypical strains." Zentralbl Bakteriol. 1991 Dec;276(1):107-19.


Wigand R., Adrian T. "A rational system for classifying and denominating adenovirus genome types." Res Virol. 1991 Jan-Feb;142(1):47-56.


Adrian T., Wolf U., Lauer HJ., Wigand R. "Restriction site mapping of adenovirus type 8 genome types." Res Virol. 1990 Nov-Dec;141(6):611-24.


Adrian T., Sassinek J., Wigand R. "Genome type analysis of 480 isolates of adenovirus types 1, 2, and 5." Arch Virol. 1990;112(3-4):235-48.


Wigand R., Adrian T. "Restriction site mapping of adenovirus prototypes of subgenus D." Med Microbiol Immunol (Berl). 1990;179(2):67-75.


Adrian T., Wolf U. "Adenovirus 6 genome types: mapping of restriction site alterations on the genome." Res Virol. 1989 Nov-Dec;140(6):545-50.


Adrian T., Schlipkoter U., Roggendorf M., Wigand R. "Nosocomial and endemic infections with a genome type of adenovirus type 5." Zentralbl Bakteriol. 1989 Sep;271(3):339-44. PMID: 2553041 [PubMed - indexed for MEDLINE]


Adrian T, Best B, Hierholzer JC, Wigand R. "Molecular epidemiology and restriction site mapping of adenovirus type 3 genome types." J Clin Microbiol. 1989 Jun;27(6):1329-34.


Adrian T., Wigand R. "Genome type analysis of certain adenovirus serotypes of subgenus D." Zentralbl Bakteriol Mikrobiol Hyg [A]. 1989 Mar;270(4):527-33.


Adrian T., Wigand R., Knocke KW., Schafer G., Grundmann M. "Genome type analysis of adenoviruses: isolates from one year from the Hannover area." Arch Virol. 1989;105(1-2):89-101.


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