Abstract
Homologous recombination is a dominant force in evolution and results in genetic mosaics. To detect evidence of recombination events and assess the biological significance of genetic mosaics, genome sequences for various viral populations of reasonably large size are now available in the GenBank. We studied a multi-functional viral gene, the adeno-associated virus (AAV) cap gene, which codes for three capsid proteins, VP1, VP2 and VP3. VP1-3 share a common C-terminal domain corresponding to VP3, which forms the viral core structure, while the VP1 unique N-terminal part contains an enzymatic domain with phospholipase A2 activity. Our recombinant detection program (RecI) revealed five novel recombination events, four of which have their cross-over points in the N-terminal, VP1 and VP2 unique region. Comparison of phylogenetic trees for different cap gene regions confirmed discordant phylogenies for the recombinant sequences. Furthermore, differences in the phylogenetic tree structures for the VP1 unique (VP1u) region and the rest of cap highlighted the mosaic nature of cap gene in the AAV population: two dominant forms of VP1u sequences were identified and these forms are linked to diverse sequences in the rest of cap gene. This observation together with the finding of frequent recombination in the VP1 and 2 unique regions suggests that this region is a recombination hot spot. Recombination events in this region preserve protein blocks of distinctive functions and contribute to convergence in VP1u and divergence of the rest of cap. Additionally the possible biological significance of two dominant VP1u forms is inferred.
Highlights
Parvoviruses are eukaryotic viruses that infect a wide variety of hosts from insects to human and non-human primates
The capsid of Associated Viruses (AAV) is formed by three proteins, VP1, VP2 and VP3 which are encoded by the same cap gene and differ in their N-terminal domain (Fig 1A)
Available AAV cap nucleotide sequences, including those of human, mammalian, avian and reptilian origins, were retrieved from Genbank and aligned (n = 156). This alignment was used for recombinant sequence screening (Fig 1) and generation of phylogenetic trees for different regions of the cap gene (Fig 2) as described in Materials and Methods
Summary
Parvoviruses are eukaryotic viruses that infect a wide variety of hosts from insects to human and non-human primates. Studies of the carnivore parvovirus subgroup have allowed the observation of cross species transmission between cat and dog populations This host range shift was due to a high mutation rate in the capsid protein gene that enabled rapid adaptation to a new cell surface receptor [1,2]. The common C-terminal domain corresponds to VP3 and folds into capsomer units that display a typical beta-barrel structure [4] with solvent exposed loops of variable amino-acids sequences. These variable regions of VP3 form the structural elements that recognize cell surface receptors. About one tenth of the capsomers are VP1 or VP2 and display additional N-terminal domains
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
