This study presents the complete genome sequence of Mokola virus, a rabies-related lyssavirus, with particular focus on characterizing its RNA-dependent RNA polymerase (L protein). The L gene spans 6,384 nucleotides encoding a 2,127 amino acid polymerase. Comparative analysis of the Mokola L protein with polymerases from other viruses in the order Mononegavirales revealed three structural domains: a divergent NH2-terminal domain, a highly conserved central domain containing most functional motifs, and a COOH-terminal domain with alternating conserved and variable regions. The researchers identified six conserved blocks across mononegavirales polymerases and conducted statistical analysis showing that glycine, acidic amino acids (aspartate and glutamate), and basic amino acids (arginine, lysine, and histidine) are significantly enriched in invariant positions, indicating strong selective pressure for their conservation. The Mokola virus genome is 11,939 nucleotides with 90% coding sequence, and phylogenetic analysis using the conserved polymerase sequences accurately reflects established taxonomic classifications within Mononegavirales families and genera, suggesting the L protein is superior to other viral proteins for phylogenetic studies.

Key findings

• The complete Mokola virus genome sequence was determined (11,939 nucleotides), with the L gene encoding a 2,127 amino acid polymerase showing three structural domains similar to other mononegavirales polymerases.
• Glycine, acidic amino acids (D, E), and basic amino acids (K, R, H) are significantly over-represented in conserved positions of polymerase sequences, indicating strong functional constraints.
• Six conserved blocks were identified in L proteins across mononegavirales, with blocks II-V in the central domain showing the highest conservation and potential genus-specific functions in the COOH-terminal domain.
• L protein sequences are superior phylogenetic markers compared to other viral proteins, accurately reflecting taxonomic relationships within the order Mononegavirales across families and genera.
• Lyssaviruses show lower L protein divergence (22% between rabies and Mokola) than vesiculoviruses (34% between VSV strains), suggesting greater flexibility for genetic exchange among lyssaviruses.