Assessment of Kinome-Wide Activity Remodeling upon Picornavirus Infection

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Picornaviridae are RNA viruses infecting humans and animals, including enteroviruses and cardioviruses.
• Viruses manipulate host cell machinery, including kinase activity, for replication.
• A comprehensive view of kinase regulation during picornavirus infection is currently lacking.

Purpose of the Study:

• To investigate the proteome-wide changes in cellular kinase activity during picornavirus infection.
• To identify specific kinases regulated by picornavirus infection.
• To assess the role of these kinases in viral replication and explore their potential as antiviral targets.

Main Methods:

• Utilized targeted mass spectrometry assays to analyze approximately 40% of the human kinome.
• Monitored kinase activity changes in cells infected with picornaviruses.
• Employed pharmacological kinase inhibitors to determine the essentiality of activated kinases for viral replication.

Main Results:

• Picornavirus infection led to the activation of mitogen-activated protein kinase (MAPK) pathway kinases (e.g., ERK1/2, JNK1/2/3, p38).
• Kinases involved in cell cycle regulation (e.g., CDK1/2, GWL, DYRK3) were inactivated upon infection.
• The DNA damage response kinase CHK2 was activated, and several activated kinases proved essential for encephalomyocarditis virus replication.

Conclusions:

• Picornavirus infection induces significant, quantifiable alterations in cellular kinome activity.
• Activated kinases, particularly those in the MAPK pathway, are critical for viral replication.
• Understanding these kinase dynamics provides a valuable resource for developing novel antiviral strategies against picornaviruses.