title: Antiviral activity of recombinant mouse β-defensin 3 against influenza A virus in vitro and in vivo.
abstract: BACKGROUND
  Influenza causes significant morbidity and mortality. Mammalian β-defensins are small peptides of about 4.5-6 kDa in mass and are effectors of the innate immune response with potent antimicrobial activity. In this paper, we focused on the anti-influenza A activity of the recombinant mouse β-defensin 3 (rMBD-3) in vivo and in vitro.
  
  
  METHODS
  The rMBD-3 peptide was added to Madin-Darby canine kidney (MDCK) cells at different stages of influenza A virus (IAV) A/PR/8/34 (H1N1) infection and its virus inhibitory properties were determined. Mice were infected with IAV and treated with rMBD-3 peptide from 12 h post-infection. The effect of rMBD-3 peptide was determined by pulmonary viral load, pathology and mortality. In addition, the expression of interleukin (IL)-12, interferon (IFN)-γ and tumour necrosis factor (TNF)-α genes in mice with or without rMBD-3 treatment was determined by semi-quantitative reverse transcriptase PCR.
  
  
  RESULTS
  rMBD-3 was shown to protect MDCK cells against IAV infection and had a major role in inhibition of adsorption and uptake by cells infected with IAV. Following the addition of 100 μg/ml rMBD-3 to MDCK cells medium, approximately 80% of cells were protected from infection in vitro. rMBD-3 given by tail vein injection (10 mg/kg/day) was the most effective method to improve the survival rate of the mice. Treatment with rMBD-3 was found to up-regulate IFN-γ and IL-12 gene expression, but reduced expression of the TNF-α gene.
  
  
  CONCLUSIONS
  These results demonstrate that rMBD-3 possesses anti-influenza virus activity both in vivo and in vitro that might be of therapeutic use.
authors.affiliation: Department of Microbiology, Guiyang Medical College, Guiyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.forename: Wanyi
authors.initials: W
authors.lastname: Li
authors.forename: Baoning
authors.initials: B
authors.lastname: Wang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Jiang
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D023083:beta-Defensins / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000998:Antiviral Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C540070:beta-defensin 3, mouse; D018664:Interleukin-12; D007371:Interferon-gamma