A two-step mechanism for RIG-I activation by influenza virus mvRNAs

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Retinoic acid-inducible gene I (RIG-I) binds noncanonical Influenza A virus (IAV) RNAs.
• Innate immune activation by these RNAs is infrequent and poorly understood.
• The sequence- and structure-dependent mechanisms of RIG-I activation remain unclear.

Purpose of the Study:

• To investigate if RIG-I activation is stimulated by noncanonical or aberrant transcription of mini viral RNAs (mvRNAs).
• To understand the role of mvRNAs, which are overexpressed in highly pathogenic IAV infections, in innate immune response.

Main Methods:

• Studied the transcription termination mechanisms of mvRNAs.
• Analyzed the role of truncated polyadenylation signals and transient RNA structures in transcription termination.
• Investigated the ability of resulting capped complementary RNAs to activate RIG-I.

Main Results:

• mvRNAs induce noncanonical transcription termination via truncated polyadenylation signals or transient 5' RNA structures.
• This termination releases mvRNA and complementary RNA, which activate RIG-I in trans.
• Sequential rounds of aberrant viral replication and transcription are necessary for IAV RNA-mediated innate immune signaling.

Conclusions:

• Aberrant transcription of mvRNAs is a key mechanism for initiating innate immune signaling during IAV infection.
• The findings elucidate a multi-step process for RIG-I activation by viral RNA synthesis.
• This provides new insights into host-pathogen interactions and viral immune evasion strategies.