ABSTRACT
Eczema vaccinatum is a potentially fatal, disseminated viral skin infection that develops in individuals with atopic dermatitis after exposure to the vaccinia virus (VV). Despite advances in modern medicine, there are few options for those suffering from disseminated VV infections. Ceragenins (CSAs) are synthetic antimicrobial compounds designed to mimic the structure and function of endogenous antimicrobial peptides (AMPs). We show that CSA-13 exhibits potent antiviral activity against VV by (1) direct antiviral effects against VV; and (2) stimulating the expression of endogenous AMPs with known antiviral activity against VV. In addition, we show that a topical application of CSA-13 penetrates the skin and reduces subsequent satellite lesion formation. This suggests that treatment with CSA-13 may be an intervention for individuals with a disseminated VV skin infection.
Subject(s)
Antiviral Agents/pharmacology , Dermatitis/drug therapy , Dermatitis/virology , Steroids/pharmacology , Vaccinia virus/drug effects , Vaccinia/drug therapy , Animals , Antiviral Agents/chemistry , Chlorocebus aethiops , Dermatitis/immunology , Humans , Keratinocytes/cytology , Keratinocytes/immunology , Keratinocytes/virology , Kidney/cytology , Mice , Mice, Hairless , Mice, SCID , Skin/virology , Steroids/chemistry , Vaccinia/immunology , Vaccinia virus/immunology , Vero Cells , Viral Envelope Proteins/immunologyABSTRACT
Degranulation of basophils and mast cells plays a central role in allergic reactions. Degranulation is a response to cell surface receptor aggregation caused by association of receptors with antibodies bound to multivalent antigens. Tools used in studying this process have included small-molecule divalent antigens, but they suffer from weak signaling apparently due to small aggregate size. We have prepared trivalent antigens that allow formation of larger aggregates and potent responses from mast cells.
