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J Virol, February 1998, p. 1438-1445, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Membrane-Associated Heparan Sulfate Proteoglycan Is
a Receptor for Adeno-Associated Virus Type 2 Virions
Candace
Summerford and
Richard Jude
Samulski*
Gene Therapy Center and Department of
Pharmacology, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina 27599
Received 22 September 1997/Accepted 28 October 1997
The human parvovirus adeno-associated virus (AAV) infects a broad
range of cell types, including human, nonhuman primate, canine, murine,
and avian. Although little is known about the initial events of virus
infection, AAV is currently being developed as a vector for human gene
therapy. Using defined mutant CHO cell lines and standard biochemical
assays, we demonstrate that heparan sulfate proteoglycans mediate both
AAV attachment to and infection of target cells. Competition
experiments using heparin, a soluble receptor analog, demonstrated
dose-dependent inhibition of AAV attachment and infection. Enzymatic
removal of heparan but not chondroitin sulfate moieties from the cell
surface greatly reduced AAV attachment and infectivity. Finally, mutant
cell lines that do not produce heparan sulfate proteoglycans were
significantly impaired for both AAV binding and infection. This is the
first report that proteoglycan has a role in cellular attachment of a
parvovirus. Together, these results demonstrate that
membrane-associated heparan sulfate proteoglycan serves as the viral
receptor for AAV type 2, and provide an explanation for the broad host
range of AAV. Identification of heparan sulfate proteoglycan as a viral receptor should facilitate development of new reagents for virus purification and provide critical information on the use of AAV as a
gene therapy vector.
*
Corresponding author. Mailing address: Gene Therapy
Center, 7119 Thurston-Bowles, CB 7352, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 962-3285. Fax: (919)
966-0907. E-mail: RJS{at}med.unc.edu.
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