The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2016 Jun 9

PMID 27276427

Citations 15

Authors

Zhihai Li

Xiaodong Yan

Hai Yu

Daning Wang

Shuo Song

Yunbing Li

Maozhou He

Qiyang Hong

Qingbing Zheng

Qinjian Zhao

Ying Gu

Jun Zhang

Mandy E W Janssen

Giovanni Cardone

Norman H Olson

Timothy S Baker

Shaowei Li

Ningshao Xia

Affiliations

Soon will be listed here.

Abstract

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.

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References

Touze A, Mahe D, El Mehdaoui S, Dupuy C, Bousarghin L, Sizaret P . The nine C-terminal amino acids of the major capsid protein of the human papillomavirus type 16 are essential for DNA binding and gene transfer capacity. FEMS Microbiol Lett. 2000; 189(1):121-7. DOI: 10.1111/j.1574-6968.2000.tb09217.x. View

Trabuco L, Schreiner E, Gumbart J, Hsin J, Villa E, Schulten K . Applications of the molecular dynamics flexible fitting method. J Struct Biol. 2010; 173(3):420-7. PMC: 3032011. DOI: 10.1016/j.jsb.2010.09.024. View

Roden R, Armstrong A, Haderer P, Christensen N, Hubbert N, Lowy D . Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope. J Virol. 1997; 71(8):6247-52. PMC: 191893. DOI: 10.1128/JVI.71.8.6247-6252.1997. View

Chen X, Garcea R, Goldberg I, Casini G, Harrison S . Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell. 2000; 5(3):557-67. DOI: 10.1016/s1097-2765(00)80449-9. View

Modis Y, Trus B, Harrison S . Atomic model of the papillomavirus capsid. EMBO J. 2002; 21(18):4754-62. PMC: 126290. DOI: 10.1093/emboj/cdf494. View

Chen V, Arendall 3rd W, Headd J, Keedy D, Immormino R, Kapral G . MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):12-21. PMC: 2803126. DOI: 10.1107/S0907444909042073. View

Zhao Q, Guo H, Wang Y, Washabaugh M, Sitrin R . Visualization of discrete L1 oligomers in human papillomavirus 16 virus-like particles by gel electrophoresis with Coomassie staining. J Virol Methods. 2005; 127(2):133-40. DOI: 10.1016/j.jviromet.2005.03.015. View

Roldao A, Mellado M, Castilho L, Carrondo M, Alves P . Virus-like particles in vaccine development. Expert Rev Vaccines. 2010; 9(10):1149-76. DOI: 10.1586/erv.10.115. View

Roden R, Kirnbauer R, Jenson A, Lowy D, Schiller J . Interaction of papillomaviruses with the cell surface. J Virol. 1994; 68(11):7260-6. PMC: 237166. DOI: 10.1128/JVI.68.11.7260-7266.1994. View

10.

Zhang X, Settembre E, Xu C, Dormitzer P, Bellamy R, Harrison S . Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction. Proc Natl Acad Sci U S A. 2008; 105(6):1867-72. PMC: 2542862. DOI: 10.1073/pnas.0711623105. View

11.

Sadeyen J, Tourne S, Shkreli M, Sizaret P, Coursaget P . Insertion of a foreign sequence on capsid surface loops of human papillomavirus type 16 virus-like particles reduces their capacity to induce neutralizing antibodies and delineates a conformational neutralizing epitope. Virology. 2003; 309(1):32-40. DOI: 10.1016/s0042-6822(02)00134-4. View

12.

Buck C, Thompson C, Pang Y, Lowy D, Schiller J . Maturation of papillomavirus capsids. J Virol. 2005; 79(5):2839-46. PMC: 548454. DOI: 10.1128/JVI.79.5.2839-2846.2005. View

13.

Trabuco L, Villa E, Mitra K, Frank J, Schulten K . Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics. Structure. 2008; 16(5):673-83. PMC: 2430731. DOI: 10.1016/j.str.2008.03.005. View

14.

Baker T, Newcomb W, Olson N, Cowsert L, Olson C, Brown J . Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J. 1991; 60(6):1445-56. PMC: 1260204. DOI: 10.1016/S0006-3495(91)82181-6. View

15.

Salunke D, Caspar D, Garcea R . Polymorphism in the assembly of polyomavirus capsid protein VP1. Biophys J. 1989; 56(5):887-900. PMC: 1280588. DOI: 10.1016/S0006-3495(89)82735-3. View

16.

Zur Hausen H . Papillomaviruses in the causation of human cancers - a brief historical account. Virology. 2009; 384(2):260-5. DOI: 10.1016/j.virol.2008.11.046. View

17.

Kucukelbir A, Sigworth F, Tagare H . Quantifying the local resolution of cryo-EM density maps. Nat Methods. 2013; 11(1):63-5. PMC: 3903095. DOI: 10.1038/nmeth.2727. View

18.

Ishii Y, Tanaka K, Kanda T . Mutational analysis of human papillomavirus type 16 major capsid protein L1: the cysteines affecting the intermolecular bonding and structure of L1-capsids. Virology. 2003; 308(1):128-36. DOI: 10.1016/s0042-6822(02)00099-5. View

19.

Delbende C, Verwaerde C, Mougel A, Tranchand Bunel D . Induction of therapeutic antibodies by vaccination against external loops of tumor-associated viral latent membrane protein. J Virol. 2009; 83(22):11734-45. PMC: 2772700. DOI: 10.1128/JVI.00578-09. View

20.

Kirnbauer R, Booy F, Cheng N, Lowy D, Schiller J . Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci U S A. 1992; 89(24):12180-4. PMC: 50722. DOI: 10.1073/pnas.89.24.12180. View