title: Distribution of sialic acid receptors and experimental infections with different subtypes of influenza A viruses in Qinghai-Tibet plateau wild pika.
abstract: BACKGROUND
  The plateau pika (Ochotona curzoniae) is a small rabbit-like mammal that lives at high altitudes in the Qinghai-Tibet plateau and is in close contact with birds. Following the outbreak of highly pathogenic avian influenza (HPAI) H5N1 during 2005 in the migratory birds of Qinghai Lake, two clades of H5N1 have been found in pikas. However, the influenza virus receptor distribution in different tissues of this animal and its susceptibility to influenza A viruses have remained unclear.
  
  
  METHODS
  The sialic acid receptor distribution tropism in pika was investigated using fluorescent Sambucus nigra and biotinylated Maackia amurensis I and II. Furthermore, the replication of three influenza A viruses H1N1, H3N2, and H5N1 in this animal was examined by immunohistochemistry and RT-PCR. Morphological and histopathological changes caused by infection were also analyzed with hematoxylin and eosin (H & E) staining.
  
  
  RESULTS
  Human influenza virus-recognizing SAα2,6Gal receptors are widely expressed in the lung, kidney, liver, spleen, duodenum, ileum, rectum, and heart, whereas avian influenza virus-recognizing SAα2,3Gal receptors are strongly expressed in the trachea and lung of pika. M1 could be detected in the lungs of pikas infected with H1N1, H3N2, and H5N1 by either immunostaining or RT-PCR, and in the brain of H5N1-infected pikas. Additionally, three subtypes of influenza A viruses were able to infect pika and caused varying degrees of pneumonia with epithelial desquamation and alveolar inflammatory cell infiltration. Slight pathological changes were observed in H1N1-infected lungs. A few small bronchi and terminal bronchioles were infiltrated by lymphocytic cells in H3N2-infected lungs. In contrast, serious lung damage, such as alveolar capillary hyperemia, edema, alveolar collapse, and lymphocytic infiltrations was observed in H5N1-infected group. Furthermore, neural system changes were present in the brains of H5N1-infected pikas.
  
  
  CONCLUSIONS
  SAα2,6Gal receptors are extensively present in many of the tissues and organs in wild plateau pika, whereas SA2,3Gal-linked receptors are dominant on the tracheal epithelial cells. H1N1, H3N2, and H5N1 were able to infect pika and caused different degrees of pathogenic changes in the lungs. Altogether, these results suggest that wild pika has the potential to be a host for different subtypes of influenza A viruses.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. sxpgly@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. xiao_hx@tib.cas.cn.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. huangbiology@126.com.
authors.forename: Chaobin
authors.initials: C
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. sunharbour@163.com.
authors.forename: Haigang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, China. lxli@nwipb.cas.cn.
authors.forename: Laixing
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. suzhang@cau.edu.cn.
authors.forename: Jingliang
authors.initials: J
authors.lastname: Su
authors.affiliation: Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. ma@im.ac.cn.
authors.forename: Juncai
authors.initials: J
authors.lastname: Ma
authors.affiliation: Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. liud@im.ac.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. twoidiots@163.com.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. liuwj@im.ac.cn.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn.|Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China. gaof@im.ac.cn.|College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. gaof@im.ac.cn.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn.|Office of Director-General, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. gaof@im.ac.cn.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: State Key Laboratory of the Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. xiangdongli68@126.com.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. yanjh@im.ac.cn.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
mesh_terms: D000820:Animal Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D000818:Animals; D005260:Female; D009980:Influenza A virus / Q000145:classification / Q000235:genetics; D007793:Lagomorpha / Q000821:virology*; D009928:Organ Specificity; D009976:Orthomyxoviridae Infections / Q000662:veterinary*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; C092488:sialic acid receptor