Molecular characterization of the heparin-dependent transduction domain on the capsid of a novel adeno-associated virus isolate, AAV(VR-942).
A new adeno-associated virus (AAV), referred to as AAV(VR-942), has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities.
Schmidt
Michael
M
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Govindasamy
Lakshmanan
L
Afione
Sandra
S
Kaludov
Nick
N
Agbandje-McKenna
Mavis
M
Chiorini
John A
JA
D000595:Amino Acid Sequence; D024361:Amino Acids, Basic; D000818:Animals; D019556:COS Cells; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D000229:Dependovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D019143:Evolution, Molecular; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014161:Transduction, Genetic
D024361:Amino Acids, Basic; D036022:Capsid Proteins; D019812:Heparan Sulfate Proteoglycans; D049452:Green Fluorescent Proteins