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.
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Michael
M
Schmidt
Lakshmanan
L
Govindasamy
Sandra
S
Afione
Nick
N
Kaludov
Mavis
M
Agbandje-McKenna
John A
JA
Chiorini
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