Yanling Feng1, Lvyin Hu2, Shuihua Lu3, Qingguo Chen3, Ye Zheng1, Dong Zeng1, Jun Zhang2, Anli Zhang4, Liang Chen5, Yunwen Hu6, Zhiyong Zhang7. 1. Department of Pathology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 2. Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 3. Department of Respiratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 4. Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 5. Department of Viral Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 6. Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 7. Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Abstract
AIMS: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
AIMS: 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 H7N9influenza virus induced an immunological response towards overt pulmonary inflammation and systemic lymphopenia which led to intense alveolar damage and respiratory failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
H7N9 influenza virus; in situ hybridization; inflammatory response;
Authors: Jørgen de Jonge; Harry van Dijken; Femke de Heij; Sanne Spijkers; Justin Mouthaan; Rineke de Jong; Paul Roholl; Eduardo Alfredo Adami; Milena Apetito Akamatsu; Paulo Lee Ho; Livia Brunner; Nicolas Collin; Martin Friede; José A Ferreira; Willem Luytjes Journal: NPJ Vaccines Date: 2020-05-11 Impact factor: 7.344