Terminal Loop Sequences in Viral Double-Stranded RNAs Modulate RIG-I Signaling

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Foreign RNA detection is key for innate immunity against viruses.
• Retinoic acid-inducible gene I (RIG-I) is a cytoplasmic sensor triggering antiviral responses via interferon (IFN) expression.
• The precise molecular triggers for RIG-I activation during viral infections are not fully understood.

Purpose of the Study:

• To investigate novel RNA structures that activate RIG-I signaling.
• To elucidate the role of RNA stem loops in RIG-I activation and IFN expression.
• To explore the potential of viral RNA motifs as immunostimulants.

Main Methods:

• Analysis of immune-activating copy-back viral genomes (cbVGs).
• Identification and characterization of RNA stem loop structures within cbVGs.
• Assessment of RIG-I signaling and IFN expression in response to viral RNA motifs.
• In vivo studies in mice using synthetic cbVG-derived stem loops.

Main Results:

• Immune-activating cbVGs possess RNA stem loops away from the 5' end that enhance RIG-I signaling and IFN production.
• The sequence of terminal loops within these motifs modulates the strength of IFN expression.
• Synthetic cbVG-derived stem loops effectively trigger innate immune responses in mice.

Conclusions:

• RNA stem loops, particularly their terminal loop sequences, are critical determinants of RIG-I activation and innate immune responses.
• These findings provide new insights into viral RNA recognition by RIG-I.
• cbVG-derived stem loops represent promising candidates for in vivo immunostimulant development.