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Low-pH-induced fusion of Vero cells infected with Junin virus
1Laboratorio de Virologia, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Abstract:
Junin virus (JV) infected Vero cells were used to investigate virus capacity to induce cell-cell fusion. Polykaryocyte formation due to JV was found to be pH and temperature-dependent. A reduced fusion activity was detected on BHK-21 cells. Different JV-strains exhibited a similar extent and pH dependence of their fusion activity. Neutralizing antibodies against the main viral glycoprotein (GP38) inhibited syncytium production and GP38 conformational changes in response to acid treatment were detected by an immunoprecipitation assay.
Insights
Junin virus (JV) causes cell fusion in a pH and temperature-dependent manner. Neutralizing antibodies targeting the viral glycoprotein (GP38) block this fusion process, indicating GP38
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Junin virus (JV) is an arenavirus responsible for Argentinian hemorrhagic fever.
- Understanding JV's cell-to-cell fusion mechanism is crucial for developing antiviral strategies.
- Viral glycoproteins often mediate cell fusion, a key step in viral entry and spread.
Purpose of the Study:
- To investigate the capacity of Junin virus to induce cell-cell fusion.
- To determine the factors influencing JV-mediated syncytia formation.
- To elucidate the role of the viral glycoprotein (GP38) in the fusion process.
Main Methods:
- Infection of Vero and BHK-21 cells with Junin virus.
- Assessment of polykaryocyte (syncytia) formation under varying pH and temperature conditions.
- Immunoprecipitation assays to detect conformational changes in GP38 upon acid treatment.
- Inhibition assays using neutralizing antibodies against GP38.
Main Results:
- Junin virus infection induced significant cell-cell fusion (polykaryocyte formation) in Vero cells.
- Fusion activity was dependent on both pH and temperature.
- BHK-21 cells showed reduced susceptibility to JV-induced fusion.
- Different JV strains displayed similar fusion extent and pH dependence.
- Neutralizing antibodies against GP38 effectively inhibited syncytium production.
- GP38 exhibited conformational changes when exposed to acidic conditions.
Conclusions:
- Junin virus possesses a potent cell-cell fusion capacity mediated by its glycoprotein, GP38.
- The fusion process is regulated by environmental factors like pH and temperature.
- GP38 undergoes acid-induced conformational changes, suggesting a role in membrane fusion.
- Targeting GP38 with neutralizing antibodies is a viable strategy to inhibit JV spread.