Human papillomavirus infection requires cell surface heparan sulfate

Using pseudoinfection of cell lines, we demonstrate that cell surface hepar an sulfate is required for infection by human papillomavirus type 16 (HPV-1 6) and HPV-33 pseudovirions. Pseudoinfection was inhibited by heparin but n ot dermatan or chondroitin sulfate, reduced by reducing the level of surfac e sulfation, and abolished by heparinase treatment. Carboxy-terminally dele ted HPV-33 virus-like particles still bound efficiently to heparin. The kin etics of postattachment neutralization by antiserum or heparin indicated th at pseudovirions were shifted on the cell surface from a heparin sensitive into a heparin-resistant mode of binding, possibly involving a secondary re ceptor. Alpha-6 integrin is not a receptor for HPV-33 pseudoinfection.