Influenza a virus antiparallel helical nucleocapsid-like pseudo-atomic structure

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Influenza A viruses cause seasonal epidemics and potential pandemics.
• Viral ribonucleoproteins (vRNPs), composed of nucleoprotein (NP) and RNA, are essential for influenza virus transcription and replication.
• Understanding vRNP structure is key to controlling influenza.

Purpose of the Study:

• To determine the high-resolution structure of an antiparallel helical RNP-like complex of influenza A virus.
• To elucidate the mechanism of RNA packaging and NP-NP interactions within vRNPs.
• To explain the inherent flexibility of influenza A virus vRNPs.

Main Methods:

• Assembly of an antiparallel helical RNP-like complex using recombinant N-terminally truncated NP and synthetic RNA.
• 3.0 Å cryo-electron microscopy (cryo-EM) structure determination.
• Analysis of RNA pathway and NP-NP interfaces.

Main Results:

• The cryo-EM structure reveals the complete RNA path through NP and details NP-NP interactions driving helical assembly.
• The structure accommodates RNA in both major and minor grooves.
• NP binds a variable number of nucleobases (estimated 20-24), explaining RNA flexibility.

Conclusions:

• The study provides unprecedented structural detail of influenza A virus vRNPs.
• Findings clarify the mechanism of genome encapsidation and the flexibility of vRNPs.
• This knowledge can inform future antiviral strategies targeting influenza virus replication.