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[Influenza encephalopathy and encephalitis]
1Department of Virology, Nagoya City University, Medical School.
Abstract:
Cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for the pathogenicity and even for the neurovirulence of influenza A viruses. WSN, a neurovirulent virus, adapted to mouse brain, grew in vitro in several types of cells including neuroblastoma cells in the absence of trypsin. When mice were intracerebrally inoculated with WSN, the viral antigen was found in the substantia nigra zona compacta and hippocampus. The mice inoculated with viruses isolated from children with acute encephalopathy associated with an influenza virus infection, on the other hand, showed no neurological symptoms. Furthermore, these viruses did not grow in the human neuroblastoma and glioblastoma cells. Since 1991, most of the human influenza A viruses have not agglutinated chicken erythrocytes. Whether this altered receptor binding specificity is related to the occurrence of influenza encephalitis and encephalopathy is now under investigation.
Insights
Neurovirulent influenza A virus (WSN) infects mouse brains, unlike human strains causing encephalopathy. This suggests altered hemagglutinin cleavage and receptor binding may influence influenza neurotropism and disease severity.
Area of Science:
- Virology
- Neuroscience
- Pathology
Context:
- Influenza A virus pathogenicity and neurovirulence depend on hemagglutinin (HA) cleavage by proteases.
- A neurovirulent strain (WSN) adapted to mouse brains can replicate in various cell types, including neuroblastoma cells, without exogenous trypsin.
- Human influenza viruses associated with acute encephalopathy do not exhibit neurovirulence in mice or replicate in human neural cell lines.
Purpose:
- To investigate the neurovirulence of influenza A virus WSN strain in a mouse model.
- To compare the in vitro growth characteristics of WSN and human influenza strains in neural cells.
- To explore the potential link between altered receptor binding specificity and the occurrence of influenza encephalitis/encephalopathy.
Summary:
- Intracerebral inoculation of WSN in mice resulted in viral antigen detection in the substantia nigra and hippocampus.
- Human influenza viruses from encephalopathy cases did not cause neurological symptoms in mice or grow in human neuroblastoma/glioblastoma cells.
- A shift in receptor binding specificity, indicated by reduced chicken erythrocyte agglutination since 1991, is being examined for its role in influenza-associated neurological diseases.
Impact:
- This research highlights differences in neurovirulence between adapted and recent human influenza A strains.
- Findings suggest that HA cleavage and receptor binding alterations may be critical factors in determining influenza neurotropism.
- The study underscores the need for further investigation into the mechanisms underlying influenza encephalitis and encephalopathy.