Numb-associated kinases regulate sandfly-borne Toscana virus entry

Area of Science:

• Virology
• Molecular Biology
• Neuroscience

Background:

• Toscana virus (TOSV), a sandfly-borne phlebovirus, is endemic in Europe and North Africa.
• TOSV causes mild febrile illness but is neurovirulent, contributing to summer meningitis.
• Limited knowledge exists regarding molecular mechanisms and host factors in phlebovirus infections.

Purpose of the Study:

• To characterize the early stages of Toscana virus infection.
• To identify host factors involved in TOSV entry.
• To evaluate potential therapeutic targets for TOSV and related phleboviruses.

Main Methods:

• Investigated early steps of TOSV infection.
• Identified host kinases regulating TOSV entry using molecular biology techniques.
• Tested FDA-approved kinase inhibitors for antiviral activity against TOSV.

Main Results:

• Adaptor-associated kinase 1 (AAK1) and cyclin G-associated kinase (GAK) were identified as key regulators of TOSV entry.
• Inhibitors targeting AAK1 and GAK demonstrated significant inhibition of TOSV infection.
• These findings highlight the role of Numb-associated kinases in TOSV pathogenesis.

Conclusions:

• AAK1 and GAK are crucial host factors for early TOSV infection.
• Targeting AAK1 and GAK with existing drugs offers a potential therapeutic strategy.
• This study provides a foundation for developing treatments against TOSV and other phleboviruses.