title: The tree shrew provides a useful alternative model for the study of influenza H1N1 virus.
abstract: BACKGROUND
  The influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human.
  
  
  METHODS
  We investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID50 and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea.
  
  
  RESULTS
  The infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue.
  
  
  CONCLUSIONS
  Based on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of influenza H1N1 virus.
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, China, Clinical Virology Division, 1 Kangda Road, Guangzhou 510230, China. jeffyah@163.com
authors.forename: Zi-feng
authors.initials: ZF
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Yu-tong
authors.initials: YT
authors.lastname: Zhu
authors.forename: Yu-tao
authors.initials: YT
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Sui-shan
authors.initials: SS
authors.lastname: Zhao
authors.forename: Run-feng
authors.initials: RF
authors.lastname: Li
authors.forename: Chun-guang
authors.initials: CG
authors.lastname: Yang
authors.forename: Ji-qiang
authors.initials: JQ
authors.lastname: Li
authors.forename: Nan-shan
authors.initials: NS
authors.lastname: Zhong
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity* / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D044967:Serum / Q000276:immunology; D014132:Trachea / Q000473:pathology / Q000821:virology; D014418:Tupaiidae / Q000821:virology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral