Heparan sulfate proteoglycans interact exclusively with conformationally intact HPV L1 assemblies: basis for a virus-like particle ELISA.
In this article, we demonstrate that interaction of human papillomavirus-like particles (HPV-VLPs) with the putative glucosaminoglycan binding receptor is strictly dependent on conformational integrity. Such conformations are present on VLPs and capsomeres but not on monomers of the major capsid protein, L1, confirming reports that capsomeres can induce virus-neutralizing antibodies. Furthermore, we show the suitability of this specific interaction for development of VLP-based enzyme-linked immunosorbent assays (ELISAs), using heparin for indirect coupling of VLPs to microtiter plates, which may add an intrinsic quality control. This avoids presentation of linear, often highly cross-reactive epitopes of L1. In addition, heparin specifically interacts with a wide variety of HPV types, making it a prime candidate for a universal capture molecule.
Rommel
Oliver
O
Virofem Diagnostica GmbH, Wiesbaden, Germany.
Dillner
Joakim
J
Fligge
Claudia
C
Bergsdorf
Christian
C
Wang
Xiaohong
X
Selinka
Hans-Christoph
HC
Sapp
Martin
M
D000914:Antibodies, Viral; D036022:Capsid Proteins; D002499:Centrifugation, Density Gradient; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D000939:Epitopes; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D027383:Papillomaviridae / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D011991:Receptors, Virus / Q000378:metabolism*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D006025:Glycosaminoglycans; C114580:HPV L1 protein, Human papillomavirus; D019812:Heparan Sulfate Proteoglycans; D009856:Oncogene Proteins, Viral; D011991:Receptors, Virus; C020341:glucosaminoglycans; D006493:Heparin