Orf virus infection of human keratinocytes and dermal fibroblasts: Limited virus detection and interference with intercellular adhesion molecule‐1 up‐regulation

Orf virus (Parapoxvirus ovis, ORFV ) is a dermatotropic virus causing pustular dermatitis in small ruminants and humans. We analysed isolated human primary keratinocytes ( KC ) and dermal fibroblasts ( FB ) for cell death and virus replication by infection with a patient‐derived ORFV isolate. ORFV infection was associated with rapid induction of cell death in KC allowing for considerable virus removal. Upon infection with ORFV , KC and FB harboured intracytoplasmic ORFV and showed viral protein presence; however, missing virus spread indicated an abortive infection. Upon ORFV exposure, KC but not FB secreted the pro‐inflammatory cytokine interleukin ( IL )‐6. ORFV infection enhanced the frequency of KC expressing intercellular adhesion molecule ( ICAM )‐1 which was independent of IL ‐6. Interestingly, ORFV inhibited ICAM ‐1 up‐regulation on infected but not on non‐infected KC . Even interferon‐γ, a potent inducer of ICAM ‐1, up‐regulated ICAM ‐1 only on non‐infected KC . Transfer of ORFV ‐free supernatant from infected to non‐infected KC induced ICAM ‐1 on non‐infected KC pointing to the involvement of soluble mediator(s). Similarly as in KC , in FB interference with ICAM ‐1 up‐regulation by ORFV infection was also observed. In conclusion, we shed light on epidermal and dermal defense mechanisms to ORFV infection and point to a novel ICAM ‐1‐related immune evasion mechanism of ORFV in human skin.