Flavivirus Capsid Proteins Inhibit the Interferon Response.

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Zika virus (ZIKV) causes persistent infections, leading to congenital defects and neurological diseases.
• ZIKV nonstructural proteins, like NS5, are known to suppress the interferon (IFN) response.
• The role of ZIKV structural proteins in modulating the host immune response remains less understood.

Purpose of the Study:

• To investigate the role of ZIKV structural proteins, specifically capsid proteins, in modulating the host immune response.
• To determine if ZIKV capsid proteins can suppress the type I interferon (IFN) pathway.

Main Methods:

• RNA-sequencing (RNA-seq) analysis to assess gene expression changes.
• Interactome assays to identify protein-protein interactions.
• In vitro ubiquitination assays to study protein modification.

Main Results:

• ZIKV capsid proteins were found to suppress the expression of type I IFN and IFN-stimulated genes across six flaviviruses.
• ZIKV capsid protein interacts with and inhibits the ubiquitination of RIG-I by TRIM25, a key host factor in IFN induction.
• Other flavivirus capsid proteins also interacted with TRIM25, indicating a conserved mechanism.

Conclusions:

• ZIKV capsid proteins play a significant role in suppressing the host's innate antiviral defense, specifically the IFN response.
• This suppression mechanism, involving interference with TRIM25 and RIG-I, may occur early in infection, potentially preceding nonstructural protein activity.
• The findings highlight a conserved strategy among flaviviruses to evade host immunity via capsid protein interactions.