Avian Influenza NS1 Proteins Inhibit Human, but Not Duck, RIG-I Ubiquitination and Interferon Signaling

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Influenza A virus nonstructural protein 1 (NS1) is a virulence factor.
• NS1 inhibits type I interferon induction, potentially by targeting the RIG-I receptor and TRIM25.
• Duck TRIM25 interaction with NS1 is uncharacterized, despite ducks being a natural reservoir.

Purpose of the Study:

• To investigate if NS1 inhibition of TRIM25 is strain-dependent and conserved in ducks.
• To compare NS1 interaction with human and duck TRIM25.
• To assess the impact on RIG-I ubiquitination and signaling in both species.

Main Methods:

• Coimmunoprecipitation and microscopy to assess NS1-TRIM25 interactions.
• Analysis of RIG-I ubiquitination and interferon promoter activity in human and duck cells.
• Use of NS1 proteins from various avian and mouse-adapted influenza A strains.

Main Results:

• Avian NS1 proteins potently inhibited human RIG-I ubiquitination and interferon production, unlike mouse-adapted PR8 NS1.
• All tested NS1 proteins suppressed interferon in infected human alveolar cells.
• Avian NS1 proteins did not suppress duck RIG-I ubiquitination or interferon production, despite interacting with duck TRIM25.

Conclusions:

• Influenza A virus NS1 proteins exhibit host-specific inhibition of the RIG-I antiviral pathway.
• Avian NS1 proteins can evade duck immune responses, contributing to their resistance to influenza.
• Understanding these host-pathogen dynamics is crucial for avian influenza surveillance and zoonotic disease prevention.