Deficiency of Cathelicidin-related Antimicrobial Peptide Promotes Skin Papillomatosis in Mus musculus Papillomavirus 1-infected Mice

Acta Derm Venereol. 2021 Jan 5;101(1):adv00367. doi: 10.2340/00015555-3733.

Abstract

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.

Keywords: CRAMP; MmuPV1; antiviral mechanisms; cathelicidin; skin papilloma; antimicrobial peptide.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Mice
  • Mice, Inbred C57BL
  • Papilloma* / chemically induced
  • Papillomaviridae* / genetics

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins