Heparan sulfate-independent cell binding and infection with furin-precleaved papillomavirus capsids.
Papillomavirus infection normally involves virion binding to cell surface heparan sulfate proteoglycans (HSPGs). However, we found that human papillomavirus type 16 pseudovirions efficiently bound and infected cells lacking HSPGs if their L2 capsid protein was precleaved by furin, a cellular protease required for infection. The inability of pseudovirions to efficiently bind and infect cultured primary keratinocytes was also overcome by furin precleavage, suggesting that the defect involves altered HSPG modification. We conclude that the primary function of HSPG binding is to enable cell surface furin cleavage of L2 and that binding to a distinct cell surface receptor(s) is a subsequent step of papillomavirus infection.
Day
Patricia M
PM
Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD,USA. pmd@nih.gov
Lowy
Douglas R
DR
Schiller
John T
JT
D002213:Capsid / Q000378:metabolism*; D002478:Cells, Cultured; D045683:Furin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D027383:Papillomaviridae / Q000378:metabolism*; D053586:Virus Internalization
D045683:Furin; D006497:Heparan Sulfate; D008024:Ligands