The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction.
Cervical cancer is the second most prevalent malignant tumor among women worldwide. High-risk human papillomaviruses (HPVs) are believed to be the major causative pathogens of mucosal epithelial cancers including cervical cancer. The HPV capsid is made up of 360 copies of major (L1) and 72 copies of minor (L2) capsid proteins. To date, limited high-resolution structural information about the HPV capsid has hindered attempts to understand details concerning the mechanisms by which HPV assembles and infects cells. In this study, we have constructed a pseudo-atomic model of the HPV59 L1-only capsid and demonstrate that the C-terminal arm of L1 participates in virus-host interactions. Moreover, when conjugated to a scaffold protein, keyhole limpet hemocyanin (KLH), this arm is immunogenic in vivo. These results provide new insights that will help elucidate HPV biology, and hence pave a way for the design of next-generation HPV vaccines.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Zhihai
Z
Li
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China; Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA; Institute of Engineering (Hangzhou), College of Engineering Peking University, Hangzhou 311121, China.
Xiaodong
X
Yan
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Hai
H
Yu
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Daning
D
Wang
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Shuo
S
Song
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Yunbing
Y
Li
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Maozhou
M
He
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Qiyang
Q
Hong
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Qingbing
Q
Zheng
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Qinjian
Q
Zhao
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Ying
Y
Gu
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Jun
J
Zhang
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA.
Mandy E W
ME
Janssen
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA.
Giovanni
G
Cardone
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA.
Norman H
NH
Olson
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA. Electronic address: tsb@ucsd.edu.
Timothy S
TS
Baker
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China. Electronic address: shaowei@xmu.edu.cn.
Shaowei
S
Li
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen University, Xiamen 361102, China.
Ningshao
N
Xia
D036022:Capsid Proteins / Q000737:chemistry* / Q000276:immunology*; D045744:Cell Line, Tumor; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology / Q000502:physiology*; D011487:Protein Conformation; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology
D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16