Immunologic characterization of human papillomavirus type 16

Abstract

Papillomaviruses (PV) are small DNA viruses which infect human and animal species, and are associated with benign and malignant proliferative lesions. Human papillomaviruses (HPV) are etiologically associated with the development of cervical cancer. Peptides from the carboxyterminus of HPV-16 L1 and L2 open reading frames (ORF)s, selected on the basis of hydrophilicity and secondary structure, were synthesized and used to generate high titered polyclonal and monoclonal anti-peptide sera. The HPV type specificity of these anti-peptide sera was determined by Western blot analysis using a panel of recombinant HPV proteins. Antisera to a HPV-16 L1 carboxyterminal peptide reacted specifically with L1 fusion proteins from HPV-16, but not with HPVs -1, -6, -11, -18, or BPV-1 or -2. Antisera to a HPV-16 L2 carboxyterminal peptide reacted with L2 proteins from HPV-16 and HPV-6, but not BPV-1. Computer analysis of carboxyterminal amino acid sequences of PV L1 proteins showed no significant homology between HPV-16 L1 and L1 proteins of other HPV types or BPV. In contrast, there was considerable similarity between carboxyterminal amino acid sequences of HPV-16 L2 and L2 proteins of other genital HPV, but not nongenital HPV or BPV. Antisera to the HPV-16 L1 peptide recognized nuclear antigen(s) in formal in-fixed, paraffin embedded cervical lesions infected with several genital HPV types, including HPV-16, 11, and 18, using immunoperoxidase techniques. Anti-L2 peptide sera did not react with capsid proteins in tissues. In addition, anti-16 L1 peptide serum immunoprecipitated an HPV-16 L1 recombinant protein, but not BPV-L2 proteins. Thus, antisera to carboxyterminal amino acids in HPV-16 major capsid proteins identified an HPV-16 type specific linear epitope in the L1 protein and a partially type-common epitope(s) in the L2 protein.;We have demonstrated antibodies reactive with bovine papillomavirus (BPV) virions in sera of many HPV-infected patients. We were unable to detect serologic responses to several HPV-16 L1 and L2 synthetic peptides. Preliminary data shows few humoral immune responses to HPV L1 recombinant proteins expressed in bacteria, but not to early PV proteins. The specificity of these responses has not been delineated.