Structural basis of oligosaccharide receptor recognition by human papillomavirus.
High risk human papillomavirus types 16 (HPV16) and 18 (HPV18) can cause cervical cancer. Efficient infection by HPV16 and HPV18 pseudovirions requires interactions of particles with cell-surface receptor heparan sulfate oligosaccharide. To understand the virus-receptor interactions for HPV infection, we determined the crystal structures of HPV16 and HPV18 capsids bound to the oligosaccharide receptor fragment using oligomeric heparin. The HPV-heparin structures revealed multiple binding sites for the highly negatively charged oligosaccharide fragment on the capsid surface, which is different from previously reported virus-receptor interactions in which a single type of binding pocket is present for a particular receptor. We performed structure-guided mutagenesis to generate mutant viruses, and cell binding and infectivity assays demonstrated the functional role of viral residues involved in heparin binding. These results provide a basis for understanding virus-heparan sulfate receptor interactions critical for HPV infection and for the potential development of inhibitors against HPV infection.
Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
Jhimli
J
Dasgupta
Malgorzata
M
Bienkowska-Haba
Marcos E
ME
Ortega
Hetalkumar D
HD
Patel
Sabrina
S
Bodevin
Dorothe
D
Spillmann
Brooke
B
Bishop
Martin
M
Sapp
Xiaojiang S
XS
Chen
D001665:Binding Sites; D018360:Crystallography, X-Ray; D006497:Heparan Sulfate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D006497:Heparan Sulfate