title: Staphylococcus aureus α-toxin modulates skin host response to viral infection.
abstract: BACKGROUND
  Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined.
  
  
  OBJECTIVE
  We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models.
  
  
  METHODS
  NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays.
  
  
  RESULTS
  We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P < .05) in murine skin inoculated with an α-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin-deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs.
  
  
  CONCLUSIONS
  The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections.
authors: Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors: Lianghua
authors: L
authors: Bin
authors: Byung Eui
authors: BE
authors: Kim
authors: Anne
authors: A
authors: Brauweiler
authors: Elena
authors: E
authors: Goleva
authors: Joanne
authors: J
authors: Streib
authors: Yinduo
authors: Y
authors: Ji
authors: Patrick M
authors: PM
authors: Schlievert
authors: Donald Y M
authors: DY
authors: Leung
mesh_terms: D051722:ADAM Proteins / Q000502:physiology; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006460:Hemolysin Proteins / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000821:virology*; D017193:Skin Diseases, Viral / Q000821:virology*; D018089:Superantigens / Q000494:pharmacology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D001427:Bacterial Toxins; D004279:DNA, Viral; D006460:Hemolysin Proteins; D008565:Membrane Proteins; D018089:Superantigens; C021091:staphylococcal alpha-toxin; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human