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Analysis of viral and cellular parameters which affect the fusion process of influenza viruses
A T Barbosa1, M O Luiz, N P Gusmão
1Departamento de Virologia, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Brasil.
Abstract:
In the present investigation we studied the fusogenic process developed by influenza A, B and C viruses on cell surfaces and different factors associated with virus and cell membrane structures. The biological activity of purified virus strains was evaluated in hemagglutination, sialidase and fusion assays. Hemolysis by influenza A, B and C viruses ranging from 77.4 to 97.2%, from 20.0 to 65.0% from 0.2 to 93.7% and from 9.0 to 76.1% was observed when human, chicken, rabbit and monkey erythrocytes, respectively, were tested at pH 5.5. At this pH, low hemolysis indexes for influenza A, B and C viruses were observed if horse erythrocytes were used as target cells for the fusion process, which could be explained by an inefficient receptor binding activity of influenza on N-glycolyl sialic acids. Differences in hemagglutinin receptor binding activity due to its specificity to N-acetyl or N-glycolyl cell surface oligosaccharides, density of these cellular receptors and level of negative charges on the cell surface may possibly explain these results, showing influence on the sialidase activity and the fusogenic process. Comparative analysis showed a lack of dependence between the sialidase and fusion activities developed by influenza B viruses. Influenza A viruses at low sialidase titers (< 2) also exhibited clearly low hemolysis at pH 5.5 (15.8%), while influenza B viruses with similarly low sialidase titers showed highly variable hemolysis indexes (0.2 to 78.0%). These results support the idea that different virus and cell-associated factors such as those presented above have a significant effect on the multifactorial fusion process.
Insights
Influenza viruses fuse with cells through a complex process influenced by viral and cellular factors. Receptor specificity and cell surface properties significantly impact viral fusion efficiency.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Influenza viruses mediate cell fusion, a critical step in viral infection.
- Understanding the factors governing this fusogenic process is key to viral pathogenesis.
Purpose of the Study:
- To investigate the fusogenic process of influenza A, B, and C viruses.
- To identify virus and cell membrane factors influencing viral fusion.
Main Methods:
- Purified influenza virus strains were used.
- Biological activity was assessed using hemagglutination, sialidase, and fusion assays.
- Hemolysis assays were performed on various erythrocytes at pH 5.5.
Main Results:
- Influenza viruses exhibited variable hemolysis across different erythrocyte types and species.
- Horse erythrocytes showed low hemolysis, potentially due to inefficient binding to N-glycolyl sialic acids.
- Sialidase activity and fusion activity showed a lack of direct dependence in influenza B viruses.
- Influenza A viruses with low sialidase titers showed low hemolysis, unlike influenza B viruses.
Conclusions:
- Viral fusion is a multifactorial process influenced by viral hemagglutinin specificity, receptor density, and cell surface charge.
- These factors collectively modulate sialidase activity and the overall fusogenic process.
- Distinct viral and cellular components significantly affect influenza virus-mediated cell fusion.