Possible bioterrorism with
smallpox has led to the resumption of
smallpox (vaccinia virus) immunization. One complication,
eczema vaccinatum, occurs primarily in patients with
atopic dermatitis (AD). Skin lesions of patients with AD, but not
psoriasis, is deficient in the
cathelicidin antimicrobial peptide (LL-37) and human beta-defensin-2 (HBD-2). We hypothesized that this defect may explain the susceptibility of patients with AD to
eczema vaccinatum. The Wyeth
vaccine strain of vaccinia virus was incubated with varying concentrations of human (LL-37) and murine (
CRAMP)
cathelicidins, human
alpha-defensin (HBD-1, HBD-2), and a control
peptide. Outcomes included quantification of viral PFU,
vaccinia viral gene expression by quantitative real-time RT-PCR, and changes in virion structure by transmission electron microscopy.
CRAMP knockout mice and control animals were inoculated by skin pricks with 2 x 10(5) PFU of
vaccinia and examined daily for pox development. Physiologic amounts of human and murine
cathelicidins (10-50 micro M), but not human
defensins, which had antibacterial activity, resulted in the in vitro reduction of
vaccinia viral plaque formation (p < 0.0001),
vaccinia mRNA expression (p < 0.001), and alteration of
vaccinia virion structure. In vivo
vaccinia pox formation occurred in four of six
CRAMP knockout animals and in only one of 15 control mice (p < 0.01). These data support a role for
cathelicidins in the inhibition of orthopox virus (
vaccinia) replication both in vitro and in vivo. Susceptibility of patients with AD to
eczema vaccinatum may be due to a deficiency of
cathelicidin.