cross-neutralization potential of native human papillomavirus n-terminal l2 epitopes交叉中和本地人类乳头状瘤病毒n端l2抗原表位的潜力.pdfVIP

Cross-Neutralization Potential of Native Human Papillomavirus N-Terminal L2 Epitopes 1 1 1 2 1 Michael J. Conway , Linda Cruz , Samina Alam , Neil David Christensen , Craig Meyers * 1 Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America, 2 Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America Abstract Background: Human papillomavirus (HPV) capsids are composed of 72 pentamers of the major capsid protein L1, and an unknown number of L2 minor capsid proteins. An N-terminal ‘‘external loop’’ of L2 contains cross-neutralizing epitopes, and native HPV16 virions extracted from 20-day-old organotypic tissues are neutralized by anti-HPV16 L2 antibodies but virus from 10-day-old cultures are not, suggesting that L2 epitopes are more exposed in mature, 20-day virions. This current study was undertaken to determine whether cross-neutralization of other HPV types is similarly dependent on time of harvest and to screen for the most effective cross-neutralizing epitope in native virions. Methodology and Principal Findings: Neutralization assays support that although HPV16 L2 epitopes were only exposed in 20-day virions, HPV31 or HPV18 epitopes behaved differently. Instead, HPV31 and HPV18 L2 epitopes were exposed in 10- day virions and remained so in 20-day virions. In contrast, presumably due to sequence divergence, HPV45 was not cross- neutralized by any of the anti-HPV16 L2 antibodies. We found that the most effective cross-neutralizing antibody was a polyclonal antibody named anti-P56/75 #1, which was raised against a peptide consisting of highly conserved HPV16 L2 amino acids 56 to 75. Co