Heparan sulfate glycosaminoglycans are involved in adenovirus type 5 and 2-host cell interactions

Gene therapy vectors derived from subgroup C adenoviruses of the serotype 5 (Ad5) and 2 (Ad2) resulted in inefficient infection of well differentiated respiratory cells, both in vitro and in vivo. The level of expression and localization of the primary receptor for Ad5 and Ad2, termed CAR, do not co mpletely explain why the infection efficiency varies greatly in different e xperimental conditions. The possibility that additional receptors like prot eoglycans are Involved in the infection of Ad5 and Ad2 was investigated, be cause several pathogenic microorganisms use heparan sulfate-glycosaminoglyc ans (HS-GAGs) as coreceptors for multistep attachment to target cells. The MS-GAG analog heparin decreased Ad5- and Ad2-mediated infection and binding starting from the concentration of 0.1 mu g/ml, up to a maximum of 50%. A similar reduction in Ad5 binding and infection was obtained by treatment of cells with heparin lyases I, II, and III but not with chondroitin ABC lyas e. The effect of heparin on Ad5 binding has not been observed in surface GA G-defective Raji cells and after treating A549 cells with heparin lyases I, II,and III. The binding of Ad5 was completely abolished when both CAR was blocked with RmcB antibody and HS-GAGs were competitively inhibited by hepa rin. Parallel experiments demonstrate that HS-GAGs are irrelevant to bindin g and infection of the subgroup B adenovirus type 3. Collectively, these re sults demonstrate for the first time that HS-GAGs expressed on the cell sur face are involved in the binding of Ad5 and Ad2 to host cells. (C) 2000 Aca demic Press.