Interactome profiling reveals the LCMV nucleoprotein co-opts DDX helicases through conserved interfaces

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• The nucleocapsid protein (NP) of lymphocytic choriomeningitis virus (LCMV) is crucial for viral replication and immune evasion.
• Its complete interactions with host proteins are not fully understood.

Purpose of the Study:

• To systematically map the global interactome of LCMV NP.
• To elucidate the functional consequences of NP-host protein interactions.

Main Methods:

• Proximity-dependent biotinylation and mass spectrometry in HEK293T cells.
• Functional enrichment analysis and genetic validation.
• All-atom molecular dynamics simulations.

Main Results:

• NP selectively binds to host RNA-binding proteins, particularly DEAD-box RNA helicases (DDX5, DDX17, DDX36, DDX56).
• These interactions dysregulate host RNA processing, translation, autophagy, and oxidative stress.
• NP-DDX5 binding induces conformational changes, potentially aiding viral RNA translation and assembly.

Conclusions:

• LCMV NP co-opts DEAD-box helicases to subvert host cell functions.
• A structural basis for replication complex assembly is provided.
• These findings suggest potential antiviral intervention strategies targeting NP-helicase interactions.