IQGAP1 and IQGAP3 are critical host factors for Marburg virus replication, nucleocapsid transport, and cell-to-cell...

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• The IQGAP protein family (IQGAP1, IQGAP2, IQGAP3) has distinct cellular roles.
• IQGAP1 was previously shown to associate with Marburg virus (MARV) inclusion bodies and nucleocapsids.

Purpose of the Study:

• To investigate the specific roles of IQGAP protein isoforms in the MARV life cycle.
• To determine how the absence of IQGAP proteins affects MARV infection and viral processes.

Main Methods:

• Generation of Huh-7 cell lines with single, combined, or triple knockouts (KOs) of IQGAP isoforms.
• Assessment of MARV transcription, replication, virus release, cell-to-cell spread, and nucleocapsid transport in IQGAP-deficient cells.
• Restoration of IQGAP expression in triple KO cells to confirm isoform functionality.

Main Results:

• Loss of IQGAP proteins reduced MARV permissiveness and impaired viral processes.
• IQGAP3 KO predominantly affected transcription and replication efficiency and virus release.
• IQGAP1 KO cells showed impaired cell-to-cell spread, while both IQGAP1 and IQGAP3 KOs altered nucleocapsid transport.
• Restoration of individual IQGAPs partially rescued the wild-type phenotype.

Conclusions:

• IQGAP proteins are critical host factors supporting MARV transcription, replication, nucleocapsid transport, and viral spread.
• IQGAPs likely modulate actin dynamics to facilitate MARV infection.
• Understanding IQGAP roles provides insights into MARV pathogenesis and potential therapeutic targets.