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Published on: December 3, 2013
The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3
Dominique Sirena1, Zsolt Ruzsics, Walter Schaffner
1Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Abstract:
Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.
Insights
Human adenovirus 3 (Ad3) causes severe respiratory infections. Researchers sequenced the Ad3 genome, revealing its genetic makeup and potential for developing new viral vector therapies.
Area of Science:
- Virology
- Genomics
- Molecular Biology
Background:
- Human adenovirus (Ad) serotype 3 is a virulent pathogen responsible for significant respiratory infections, comprising approximately 13% of all Ad isolates.
- Understanding the genetic makeup of Ad3 is crucial for elucidating its pathogenicity and developing effective therapeutic strategies.
Purpose of the Study:
- To report the complete DNA sequence of the human adenovirus 3 (Ad3).
- To analyze the genomic organization and nucleotide identity of Ad3 in comparison to other adenovirus serotypes.
- To generate a recombinant E1-deleted Ad3 for potential therapeutic applications.
Main Methods:
- Complete genome sequencing of Ad3 (35,343 base pairs).
- Comparative nucleotide sequence analysis with related adenovirus serotypes (Ad7, Ad11, Ad5).
- Genomic organization analysis, identifying transcription units and open reading frames.
- Construction of a recombinant E1-deleted Ad3 using a bacterial artificial chromosome.
Main Results:
- The complete Ad3 DNA sequence was determined (GenBank accession DQ086466).
- Ad3 exhibits high nucleotide identity (96.43%) with Ad7, moderate identity with Ad11 (82.56%), and lower identity with Ad5 (62.75%).
- The genomic organization is conserved among human adenoviruses, featuring multiple transcription units and open reading frames.
- A recombinant E1-deleted Ad3 demonstrated efficient transduction of CD46-positive cells.
Conclusions:
- The Ad3 genome sequence provides a foundation for understanding its biology and pathogenesis.
- The characterized genomic organization and sequence identity offer insights into adenovirus evolution and virulence.
- The development of an E1-deleted Ad3 vector shows promise for enhancing gene therapy and other clinical applications.
