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Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication
Laura Albentosa-González1, Rosario Sabariegos1,2,3, Armando Arias1,3,4
1Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, C/Almansa 14, 02008 Albacete, Spain.
Pathogens (Basel, Switzerland)
|March 6, 2021
Summary
Usutu virus (USUV) replication involves the cellular kinase Akt. Inhibiting Akt significantly reduced USUV titers, suggesting Akt is a potential antiviral target for controlling this emerging flavivirus.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Usutu virus (USUV) is an emerging flavivirus primarily infecting birds via mosquitoes, with increasing human health concerns.
- Limited data exists on USUV's host cell targets, hindering effective infection control strategies.
Purpose of the Study:
- To investigate the interaction and co-localization between cellular kinase Akt and USUV polymerase NS5.
- To determine if Akt phosphorylates NS5 and its role in viral replication.
Main Methods:
- Co-immunoprecipitation (Co-IP) assays to assess protein interaction.
- Confocal microscopy to confirm protein co-localization.
- In vitro kinase assays to test NS5 phosphorylation by Akt.
- Chemical silencing of Akt using inhibitors (MK-2206, honokiol, ipatasertib) in infected cells.
Main Results:
- Akt and USUV NS5 were found to interact and co-localize within cells.
- Akt was confirmed to phosphorylate NS5 in vitro.
- Inhibition of Akt led to a significant decrease (>10-fold) in USUV titers in infected cells.
Conclusions:
- The cellular kinase Akt plays a crucial role in Usutu virus replication.
- The PI3K/Akt/mTOR pathway represents a promising antiviral target for USUV infection control.
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