title: Differential dependence on host cell glycosaminoglycans for infection of epithelial cells by high-risk HPV types.
abstract: Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind and enter through a GAG-independent mechanism. Infections of primary human keratinocytes, natural host cells for HPV infections, support our conclusions. Further, this renders the different virus types differentially susceptible to carrageenan, a microbicide targeting virus entry. Our data demonstrates that ordered maturation of papillomavirus particles in a differentiating epithelium may alter the virus entry mechanism. This study should facilitate a better understanding of the attachment and infection by the main oncogenic HPV types, and development of inhibitors of HPV infection.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Cruz
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
mesh_terms: D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D002704:Chlorates / Q000494:pharmacology; D005260:Female; D006025:Glycosaminoglycans / Q000172:deficiency / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D052161:Human papillomavirus 18 / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D058952:Human papillomavirus 31 / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D013045:Species Specificity; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
chemical_list: D002704:Chlorates; D006025:Glycosaminoglycans; D002351:Carrageenan; D006493:Heparin; C032706:sodium chlorate