MEMBRANE-ASSOCIATED HEPARAN-SULFATE PROTEOGLYCAN IS A RECEPTOR FOR ADENOASSOCIATED VIRUS TYPE-2 VIRIONS

The human parvovirus adeno-associated virus (AAV) infects a broad rang e of cell types, including human, nonhuman primate, canine, murine, an d avian. Although little is known about the initial events of virus in fection, AAV is currently being developed as a vector for human gene t herapy, Using defined mutant CHO cell lines and standard biochemical a ssays, we demonstrate that heparan sulfate proteoglycans mediate both AAV attachment to and infection of target cells, Competition experimen ts using heparin, a soluble receptor analog, demonstrated dose-depende nt inhibition of AAV attachment and infection, Enzymatic removal of he paran but not chondroitin sulfate moieties fi om the cell surface grea tly reduced AAV attachment and infectivity. Finally, mutant cell lines that do not produce heparan sulfate proteoglycans Here significantly impaired for both AAV binding and infection, This is the first report that proteoglycan has a role in cellular attachment of a parvovirus, T ogether, these results demonstrate that membrane-associated heparan su lfate proteoglycan serves as the viral receptor for AAV type 2, and pr ovide an explanation for the broad host range of AAV. Identification o f heparan sulfate proteoglycan as a viral receptor should facilitate d evelopment of new reagents for virus purification and provide critical information on the use of AAV as a gene therapy vector.