Sonja Dorfer, Katharina Strasser, Siegfried Reipert, Michael B. Fischer, Saeed Shafti-Keramat, Michael Bonelli, Georg Schröckenfuchs, Wolfgang Bauer, Stefanie Kancz, Lena Müller, Alessandra Handisurya
DOI: 10.2340/00015555-3733

Cathelicidins have been reported to inhibit human papillomavirus infection in vitro; however, nothing is known about their activity in vivo. In this study, experimental skin infection with Mus musculus papillomavirus 1 resulted in robust development of cutaneous papillomas in cyclosporine A-treated C57BL/6J mice deficient for the murine cathelicidin-related antimicrobial peptide (CRAMP), in contrast to wild-type controls. Analysis of the underlying mechanisms revealed moderate disruption of virion integrity and lack of interference with viral entry and intracellular trafficking by a synthetic CRAMP peptide. Differences in the immune response to Mus musculus papillomavirus 1 infection were observed between CRAMP-deficient and wild-type mice. These included a stronger reduction in CD4+ and CD8+ T-cell numbers in infected skin, and lack of Mus musculus papillomavirus 1-specific neutralizing antibodies in response to cyclosporine A in the absence of endogenous CRAMP. CRAMP has modest direct anti-papillomaviral effects in vitro, but exerts protective functions against Mus musculus papillomavirus 1 skin infection and disease development in vivo, primarily by modulation of cellular and humoral immunity.

Cathelicidins are host defence (antimicrobial) peptides. This study demonstrates that mice, which lack the murine cathelicidin-related antimicrobial peptide in their skin and immune cells, consistently developed large papillomas on the skin after infection with a mouse papillomavirus and concomitant immunosuppression. In contrast, the presence of cathelicidin-related antimicrobial peptide in control mice was protective against development of skin papillomas. The cathelicidin-related antimicrobial peptide-mediated protection against papillomavirus skin infection and associated disease was mediated by modulation of the host’s immune system. These results indicate cathelicidins as important targets for future anti-papillomaviral compounds.

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