The PI3K/Akt pathway contributes to arenavirus budding

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Arenaviruses, including Lassa virus (LASV), cause significant human hemorrhagic fever (HF).
• Lymphocytic choriomeningitis virus (LCMV), a globally distributed arenavirus, is a neglected human pathogen.
• The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is crucial for cellular processes and viral replication.

Purpose of the Study:

• To investigate the role of the PI3K/Akt pathway in the life cycle of LCMV.
• To evaluate the potential of PI3K/Akt pathway inhibition as an antiviral strategy against LCMV.

Main Methods:

• Inhibition of the PI3K/Akt pathway in cultured cells infected with LCMV.
• Assessment of viral RNA synthesis and budding upon pathway inhibition.
• Treatment of LCMV-infected cells with BEZ-235, a PI3K inhibitor.

Main Results:

• Inhibition of the PI3K/Akt pathway significantly reduced LCMV budding and, to a lesser extent, RNA synthesis.
• Cell entry of LCMV was not affected by PI3K/Akt pathway inhibition.
• The PI3K inhibitor BEZ-235 effectively inhibited LCMV multiplication in cell culture.

Conclusions:

• The PI3K/Akt pathway is essential for LCMV replication, particularly for viral budding.
• Targeting the PI3K/Akt pathway represents a promising antiviral approach for human-pathogenic arenaviruses, including LCMV and Junin virus (JUNV).