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

Abstract

AimsTo investigate the histopathological manifestations of two fatal cases of H7N9 influenza A virus infection.MethodsPulmonary 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.

Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains

“…Both granulocytosis (as part of the acute phase reaction) and lymphopenia have been well documented in viral pneumonia in humans (e.g. [13]). The temporary drop in lymphocytes, which is the stronger determinant of the early changes in GRA/LYM and LYM% in both mouse strains (Figure 2) might be due to migration/retention of lymphocytes in lung and/or lymphoid tissue.…”

Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment

“…Drug repurposing, or the use of clinical drug candidates, may help to overcome this lengthy process of drug development and reduce the impact of H7N9‐induced disease. H7N9 disease results in a potent immune response believed to contribute to tissue destruction and pathology 16 . The host's immune response towards H7N9 infection has not been fully characterized, which is an issue for the discovery of novel therapeutics and target identification for drug repurposing.…”

“…In studies of fatal H7N9 infections in humans, there is evidence of immune pathological changes caused by a heightened innate immune response 16 . Proliferation of H7N9 in the lower respiratory tract causes excessive activation of the innate immune response 16 . This leads to production of inflammatory mediators, many expressed by intrapulmonary macrophages and alveolar cells 16 .…”

“…Proliferation of H7N9 in the lower respiratory tract causes excessive activation of the innate immune response 16 . This leads to production of inflammatory mediators, many expressed by intrapulmonary macrophages and alveolar cells 16 . Some of the major histological characteristics of H7N9 infection include diffuse alveolar damage, hyaline membrane and fibroproliferation in the lung, and spotty necrosis in the liver 16 .…”

“…This leads to production of inflammatory mediators, many expressed by intrapulmonary macrophages and alveolar cells 16 . Some of the major histological characteristics of H7N9 infection include diffuse alveolar damage, hyaline membrane and fibroproliferation in the lung, and spotty necrosis in the liver 16 . Histological observations have shown a depletion of T cells, a fluctuating numbers of neutrophils, and highly abundant and activated macrophages which are characteristic of H7N9 infection in the alveoli 16 .…”