title: Pulmonary fibrosis induced by H5N1 viral infection in mice.
abstract: BACKGROUND
  Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus.
  
  
  METHODS
  Eight-week-old BALB/c mice were inoculated intranasally with 1 x 101 MID50 of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation.
  
  
  RESULTS
  H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice.
  
  
  CONCLUSIONS
  Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.
authors.affiliation: Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. qiaojian@cau.edu.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Qiao
authors.forename: Miaojie
authors.initials: M
authors.lastname: Zhang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Bi
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Guangcun
authors.initials: G
authors.lastname: Deng
authors.forename: Guimei
authors.initials: G
authors.lastname: He
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Luan
authors.forename: Nana
authors.initials: N
authors.lastname: Lv
authors.forename: Tong
authors.initials: T
authors.lastname: Xu
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000150:complications / Q000821:virology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000821:virology; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000821:virology
chemical_list: D003094:Collagen; D006909:Hydroxyproline