Non-heparan sulfate GAG-dependent infection of cells using an adenoviral vector with a chimeric fiber conserving its KKTK motif

Recently, the potential involvement of the putative heparan sulfate proteoglycans (HSPG) binding motif, KKTK, in mediating HAdV-5 liver cell infection following intravascular virus delivery has been debated. In the present study, we demonstrated that HSPGs were not involved in the in vitro infection process of an adenoviral vector harboring chimeric fibers without mutation in the KKTK motif, HAdV-5-F2/BAdV-4. The entry of HAdV-5-F2/BAdV-4 into cells occurs by two mechanisms 1) the attachment of HAdV-5-F2/BAdV-4 to the surface of cells requires N-glycosylation, 2) the uptake of the virus is effective after interaction with a co-receptor, putatively the chondroitin sulfate C. Together, these results contribute to improving our understanding of the molecular mechanisms determining HAdV's infectivity in vitro and may aid in designing novel HAdV-based vectors for gene therapy applications.