Deficiency of cathelicidin-related antimicrobial peptide promotes skin papillomatosis in mus musculus papillomavirus 1-infected mice

Abstract

ActaDVADmVCathelicidins have been reported to inhibit human papillomavirus infection in vitro; however, nothing is known about their activity in vivo. In this study, exper-imental skin infection with Mus musculus papilloma-virus 1 resulted in robust development of cutaneous papillomas in cyclosporine A-treated C57BL/6J mice deficient for the murine cathelicidin-related antimicro-bial peptide (CRAMP), in contrast to wild-type controls. Analysis of the underlying mechanisms revealed mo-derate disruption of virion integrity and lack of inter-ference 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 ab sence 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.