Pulmonary fibrosis induced by H5N1 viral infection in mice.
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.
Qiao
Jian
J
Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. qiaojian@cau.edu.cn
Zhang
Miaojie
M
Bi
Jianmin
J
Wang
Xun
X
Deng
Guangcun
G
He
Guimei
G
Luan
Zhihua
Z
Lv
Nana
N
Xu
Tong
T
Zhao
Lihong
L
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
D003094:Collagen; D006909:Hydroxyproline