title: Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus.
abstract: A new avian-origin influenza virus A (H7N9) recently crossed the species barrier and infected humans; therefore, there is an urgent need to establish mammalian animal models for studying the pathogenic mechanism of this strain and the immunological response. In this study, we attempted to develop mouse models of H7N9 infection because mice are traditionally the most convenient models for studying influenza viruses. We showed that the novel A (H7N9) virus isolated from a patient could infect inbred BALB/c and C57BL/6 mice as well as outbred Institute of Cancer Research (ICR) mice. The amount of bodyweight lost showed differences at 7 days post infection (d.p.i.) (BALB/c mice 30%, C57BL/6 and ICR mice approximately 20%), and the lung indexes were increased both at 3 d.p.i. and at 7 d.p.i.. Immunohistochemistry demonstrated the existence of the H7N9 viruses in the lungs of the infected mice, and these findings were verified by quantitative real-time polymerase chain reaction (RT-PCR) and 50% tissue culture infectious dose (TCID50) detection at 3 d.p.i. and 7 d.p.i.. Histopathological changes occurred in the infected lungs, including pulmonary interstitial inflammatory lesions, pulmonary oedema and haemorrhages. Furthermore, because the most clinically severe cases were in elderly patients, we analysed the H7N9 infections in both young and old ICR mice. The old ICR mice showed more severe infections with more bodyweight lost and a higher lung index than the young ICR mice. Compared with the young ICR mice, the old mice showed a delayed clearance of the H7N9 virus and higher inflammation in the lungs. Thus, old ICR mice could partially mimic the more severe illness in elderly patients.
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Bisheng
authors.initials: B
authors.lastname: Shi
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Xu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Boyin
authors.initials: B
authors.lastname: Qin
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Guan
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China.
authors.forename: Wenjiang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China ; Key laboratory of Medical Molecular Virology of the Ministries of Education, School of Basic Medical Science, Fudan Univeristy, Shanghai 200032, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University , Shanghai 201508, China ; Key laboratory of Medical Molecular Virology of the Ministries of Education, School of Basic Medical Science, Fudan Univeristy, Shanghai 200032, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
keywords: H7N9; avian influenza virus; mice