title: H5N1 infection of the respiratory tract and beyond: a molecular pathology study.
abstract: BACKGROUND
  Human infection with avian influenza H5N1 is an emerging infectious disease characterised by respiratory symptoms and a high fatality rate. Previous studies have shown that the human infection with avian influenza H5N1 could also target organs apart from the lungs.
  
  
  METHODS
  We studied post-mortem tissues of two adults (one man and one pregnant woman) infected with H5N1 influenza virus, and a fetus carried by the woman. In-situ hybridisation (with sense and antisense probes to haemagglutinin and nucleoprotein) and immunohistochemistry (with monoclonal antibodies to haemagglutinin and nucleoprotein) were done on selected tissues. Reverse-transcriptase (RT) PCR, real-time RT-PCR, strand-specific RT-PCR, and nucleic acid sequence-based amplification (NASBA) detection assays were also undertaken to detect viral RNA in organ tissue samples.
  
  
  RESULTS
  We detected viral genomic sequences and antigens in type II epithelial cells of the lungs, ciliated and non-ciliated epithelial cells of the trachea, T cells of the lymph node, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. Viral genomic sequences (but no viral antigens) were detected in the intestinal mucosa. In the fetus, we found viral sequences and antigens in the lungs, circulating mononuclear cells, and macrophages of the liver. The presence of viral sequences in the organs and the fetus was also confirmed by RT-PCR, strand-specific RT-PCR, real-time RT-PCR, and NASBA.
  
  
  CONCLUSIONS
  In addition to the lungs, H5N1 influenza virus infects the trachea and disseminates to other organs including the brain. The virus could also be transmitted from mother to fetus across the placenta.
authors: Infectious Disease Centre, Peking University, Beijing, China. jianggu@bjmu.edu.cn
authors: Jiang
authors: J
authors: Gu
authors: Zhigang
authors: Z
authors: Xie
authors: Zhancheng
authors: Z
authors: Gao
authors: Jinhua
authors: J
authors: Liu
authors: Christine
authors: C
authors: Korteweg
authors: Juxiang
authors: J
authors: Ye
authors: Lok Ting
authors: LT
authors: Lau
authors: Jie
authors: J
authors: Lu
authors: Zifen
authors: Z
authors: Gao
authors: Bo
authors: B
authors: Zhang
authors: Michael A
authors: MA
authors: McNutt
authors: Min
authors: M
authors: Lu
authors: Virginia M
authors: VM
authors: Anderson
authors: Encong
authors: E
authors: Gong
authors: Albert Cheung Hoi
authors: AC
authors: Yu
authors: W Ian
authors: WI
authors: Lipkin
mesh_terms: D000328:Adult; D005260:Female; D005333:Fetus / Q000473:pathology*; D016679:Genome, Viral; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D018445:Infectious Disease Transmission, Vertical; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D007251:Influenza, Human / Q000473:pathology* / Q000635:transmission / Q000821:virology; D008297:Male; D011247:Pregnancy; D012137:Respiratory System / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021161:Self-Sustained Sequence Replication / Q000379:methods