Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus.
OBJECTIVE
To investigate the histopathological manifestations of two fatal cases of H7N9 influenza A virus infection.


METHODS
Pulmonary and hepatic specimens from two fatal cases of H7N9 influenza virus infection were examined using H&E staining. Additionally, in situ hybridisation was performed with probes (ViewRNA) targeting H7N9 RNA and IP-10, interleukin (IL)-6 mRNA. The distribution of surfactant protein A (SP-A), surfactant protein B (SP-B), CD3, CD4, CD8, CD68 and C4d were determined with immunohistochemistry.


RESULTS
Apart from the typical diffuse alveolar damage and hyaline membrane observed in severe influenza infection, we detected H7N9 RNA and massive intrapulmonary production of IP-10 and IL-6 mRNA using in situ hybridisation. Hyperplasia of type II pneumocytes was observed by H&E staining and immunohistochemistry. Proliferating macrophages and clustered neutrophils in the infected lungs were observed, whereas T lymphocytes, especially CD4T helper cells, were markedly depleted. No obvious complement deposition was found in lung tissues.


CONCLUSIONS
Our findings suggest that H7N9 influenza virus induced an immunological response towards overt pulmonary inflammation and systemic lymphopenia which led to intense alveolar damage and respiratory failure.
Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Yanling
Y
Feng
Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Lvyin
L
Hu
Department of Respiratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Shuihua
S
Lu
Department of Respiratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Qingguo
Q
Chen
Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Ye
Y
Zheng
Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Dong
D
Zeng
Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Jun
J
Zhang
Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Anli
A
Zhang
Department of Viral Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Liang
L
Chen
Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Yunwen
Y
Hu
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Zhiyong
Z
Zhang
D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D064766:Influenza A Virus, H7N9 Subtype; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057089:Pathology, Molecular; D011663:Pulmonary Surfactants / Q000032:analysis
D015703:Antigens, CD; D011663:Pulmonary Surfactants
H7N9 influenza virus; in situ hybridization; inflammatory response;