Cutaneous infections of mice with vaccinia or cowpox viruses and efficacy of cidofovir

Abstract

Orthopoxviruses, including smallpox, monkeypox and molluscipox, pose risks to human health through bioterrorist acts or natural transmission. There is no approved therapy for orthopoxvirus infections; however, cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of adverse effects following smallpox vaccination. For evaluation of new therapies directed against orthopoxvirus infections, we have utilized immunocompetent, hairless mice (SKH-1) inoculated by a cutaneous route with cowpox virus (CV) or vaccinia virus (VV). Mice subsequently developed skin lesions and virus was recovered from the site of inoculation and quantified. Skin biopsies were evaluated microscopically, revealing brick-like eosinophilic, intracytoplasmic inclusion bodies characteristic of orthopoxvirus infection. SKH-1 mice fully recovered from either CV or VV infection. Immunodeficient Athymic or Rhino mice inoculated with CV or VV had more lesions and severe disease than SKH-1 mice. CV-infected SKH-1 mice were treated either with systemic or topical CDV. Although some protection was achieved with systemic treatment, 5% topical CDV was most effective at reducing virus titers in skin, lung, kidney, and spleen. These models may provide a means for evaluating efficacy of new therapies directed against orthopoxvirus diseases and further confirm the topical activity of CDV against cutaneous infections.

Fig. 1

(A) Orofacial area of SKH-1 mouse. White arrow indicates site of inoculation. Yellow arrow indicates general location of facial skin lesions. (B) Rash-like lesions on infected SKH-1 mouse. (C) Vesicular lesions on lateral thorax. (D) Histopathology of biopsy of vesicular lesion from CV-infected SKH-1 mouse 6 days post-viral inoculation.

Fig. 2

Alteration of VV–WR virus titers in organs of SKH-1 mice treated topically three times daily with 5% CDV or i.p. once daily with 50 mg/kg CDV beginning at 24 h after infection and continued through day 7.