Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization

Journal Article · Tue Sep 15 04:00:00 EDT 2015 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2015.04.016· OSTI ID:22470188

Guan, Jian ^[1]; Bywaters, Stephanie M.; Brendle, Sarah A. ^[2]; Lee, Hyunwook; Ashley, Robert E. ^[1]; Makhov, Alexander M.; Conway, James F. ^[3]; Christensen, Neil D. ^[2]; Hafenstein, Susan ^[1]

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1. Department of Medicine, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 (United States)
2. Department of Pathology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 (United States)
3. Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Ave, Pittsburgh, PA 15260 (United States)

Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays. - Highlights: • We present HPV16-Fab complexes from neutralizing mAbs: H16.1A, H16.14J, and H263.A2. • The structure-function analysis revealed predominantly monovalent binding of each mAb. • Capsid–Fab interactions involved multiple loops from symmetry related L1 proteins. • Besides the known FG and HI loops, epitope mapping also identified DE, EF, and BC loops. • Neutralizing assays complement the structures to show multiple neutralization mechanisms.

• OSTI ID: 22470188
• Journal Information: Virology, Journal Name: Virology Vol. 483; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
COMPARATIVE EVALUATIONS
CROSS-LINKING
ELECTRON MICROSCOPY
HUMAN POPULATIONS
INTERACTIONS
STRUCTURE FUNCTIONS
SURFACES
VIRUSES