AUTHOR=Hasche Daniel , Ahmels Melinda , Braspenning-Wesch Ilona , Stephan Sonja , Cao Rui , Schmidt Gabriele , Müller Martin , Rösl Frank 

TITLE=Isoforms of the Papillomavirus Major Capsid Protein Differ in Their Ability to Block Viral Spread and Tumor Formation

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.811094

DOI=10.3389/fimmu.2022.811094

ISSN=1664-3224

ABSTRACT=<p>Notably, the majority of papillomaviruses associated with a high cancer risk have the potential to translate different isoforms of the L1 major capsid protein. In an infection model, the cutaneous <italic>Mastomys natalensis</italic> papillomavirus (MnPV) circumvents the humoral immune response of its natural host by first expressing a 30 amino acid extended L1 isoform (L1<sub>LONG</sub>). Although inducing a robust seroconversion, the raised antibodies are not neutralizing <italic>in vitro</italic>. In contrast, neutralizing antibodies induced by the capsid-forming isoform (L1<sub>SHORT</sub>) appear delayed by several months. We now provide evidence that, although L1<sub>LONG</sub> vaccination showed a strong seroconversion, these antibodies were not protective. As a consequence, virus-free animals subsequently infected with MnPV still accumulated high numbers of transcriptionally active viral genomes, ultimately leading to skin tumor formation. In contrast, vaccination with L1<sub>SHORT</sub> was completely protective. This shows that papillomavirus L1<sub>LONG</sub> expression is a unique strategy to escape from antiviral immune surveillance.</p>