H5N1 infection of the respiratory tract and beyond: a molecular pathology study.
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.
Gu
Jiang
J
Infectious Disease Centre, Peking University, Beijing, China. jianggu@bjmu.edu.cn
Xie
Zhigang
Z
Gao
Zhancheng
Z
Liu
Jinhua
J
Korteweg
Christine
C
Ye
Juxiang
J
Lau
Lok Ting
LT
Lu
Jie
J
Gao
Zifen
Z
Zhang
Bo
B
McNutt
Michael A
MA
Lu
Min
M
Anderson
Virginia M
VM
Gong
Encong
E
Yu
Albert Cheung Hoi
AC
Lipkin
W Ian
WI
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