Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus

J Clin Pathol. 2015 Jan;68(1):57-63. doi: 10.1136/jclinpath-2014-202441. Epub 2014 Nov 6.

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.

Keywords: H7N9 influenza virus; in situ hybridization; inflammatory response;.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Animals
  • Antigens, CD / analysis
  • Antigens, CD / biosynthesis
  • Fatal Outcome
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Influenza A Virus, H7N9 Subtype*
  • Influenza, Human / immunology*
  • Influenza, Human / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pathology, Molecular
  • Pulmonary Surfactants / analysis

Substances

  • Antigens, CD
  • Pulmonary Surfactants