Deficiency of Cathelicidin-related Antimicrobial Peptide Promotes Skin Papillomatosis in Mus musculus Papillomavirus 1-infected Mice
DOI:
https://doi.org/10.2340/00015555-3733Keywords:
antimicrobial peptide, cathelicidin, CRAMP, MmuPV1, skin papilloma, antiviral mechanismsAbstract
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.
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Copyright (c) 2021 Sonja Dorfer, Katharina Strasser, Siegfried Reipert, Michael B. Fischer, Saeed Shafti-Keramat, Michael Bonelli, Georg Schröckenfuchs, Wolfgang Bauer, Stefanie Kancz, Lena Müller, Alessandra Handisurya
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