Henipavirus W Proteins Interact with 14-3-3 To Modulate Host Gene Expression

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Nipah virus (NiV) and Hendra virus (HeV) are highly lethal zoonotic pathogens belonging to the Henipavirus genus.
• The W protein, expressed via mRNA editing from the P gene, plays a role in modulating innate immune responses.
• The precise host interactions enabling W protein's immune modulation remain incompletely understood.

Purpose of the Study:

• To investigate the host interactions of NiV and HeV W proteins in modulating innate immunity.
• To elucidate the role of 14-3-3 proteins in henipavirus pathogenesis.
• To identify novel functions of the W protein in host cellular processes.

Main Methods:

• Co-crystallization of the NiV W protein C-terminal binding motif with 14-3-3.
• Interaction studies between NiV/HeV W proteins and all seven isoforms of 14-3-3.
• Transcriptomic analysis of cells expressing wild-type or mutant W proteins.

Main Results:

• NiV and HeV W proteins interact with all seven isoforms of 14-3-3, dependent on a phosphorylated serine residue.
• The cocrystal structure provides insights into the Mode III 14-3-3 binding motif.
• Transcriptomic analysis revealed W protein's regulation of cellular metabolism, extracellular matrix organization, and apoptosis.

Conclusions:

• The interaction between henipavirus W proteins and 14-3-3 proteins is a key mechanism for modulating host innate immunity.
• This interaction influences cellular metabolic processes, extracellular matrix organization, and apoptosis, suggesting new therapeutic targets.
• Structural and functional characterization of the W:14-3-3 complex advances understanding of henipavirus-host interactions.