Structural and Functional Motifs in Influenza Virus RNAs

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• Influenza A viruses (IAV) cause significant human and animal epidemics and pandemics.
• IAV possess an eight-segment negative-sense viral RNA (vRNA) genome, forming ribonucleoproteins (vRNPs).
• Viral RNA replication and transcription involve vRNAs, complementary RNAs (cRNAs), and viral messenger RNAs (vmRNAs) with distinct structural and functional properties.

Purpose of the Study:

• To compile and review known structural motifs within the different RNA classes of influenza A viruses.
• To elucidate the functional roles of these RNA structural motifs in the viral replication cycle.
• To highlight the current state and future directions of structural studies on viral RNAs.

Main Methods:

• Review of existing literature on influenza A virus RNA structures.
• Analysis of structural studies using techniques like in vitro RNA probing, crosslinking, and next-generation RNA sequencing.
• Integration of findings from bioinformatics predictions and experimental validation of RNA structures.

Main Results:

• Structural motifs in viral RNA promoters are critical for polymerase binding and function.
• Complementary RNAs (cRNAs) form ribonucleoproteins (cRNPs) and serve as templates for vRNA synthesis.
• Viral messenger RNAs (vmRNAs) possess unique 5' cap-snatching and 3' polyadenylation, with some requiring splicing for protein synthesis.

Conclusions:

• Recent advancements in structural biology, particularly for the influenza polymerase complex, have enhanced understanding of viral RNA processes.
• Structural studies of vRNAs within native vRNPs and experimentally validated vmRNA structures are advancing rapidly.
• A comprehensive understanding of viral RNA structures is essential for deciphering the influenza A virus life cycle and developing targeted therapeutics.