Structure of a rabies virus polymerase complex from electron cryo-microscopy

Area of Science:

• Structural Biology
• Virology
• Molecular Biology

Background:

• Nonsegmented negative-stranded (NNS) RNA viruses, including rabies virus (RABV), are significant human pathogens.
• The viral large polymerase (L) protein is essential for transcription and replication, possessing RNA polymerization, mRNA capping, and cap methylation activities.

Purpose of the Study:

• To elucidate the structural basis of NNS RNA virus transcription and replication.
• To characterize the complete structure of the RABV L-P complex.

Main Methods:

• Electron cryo-microscopy (cryo-EM) was employed to determine the structure.
• The resolution achieved was 3.3 Å.

Main Results:

• The complete structure of the RABV L protein bound to its phosphoprotein cofactor (P) was determined.
• The RABV L-P complex structure closely resembles that of vesicular stomatitis virus (VSV) L-P, with notable local differences.
• The determined structure represents a preinitiation conformation, distinct from elongation complexes of other NNS RNA viruses.
• Analysis of internal cavities suggests specific pathways for template and product entry/exit during RNA synthesis.

Conclusions:

• The structural data provides a detailed view of the RABV L-P complex in a preinitiation state.
• Comparison with other viral polymerase structures highlights differences between initiation and elongation complexes.
• Understanding these structural features can inform the development of antiviral strategies targeting viral RNA synthesis.