Nonsegmented Negative-Sense RNA Viruses-Structural Data Bring New Insights Into Nucleocapsid Assembly

Viruses with a nonsegmented negative-sense RNA genome (NNVs) include important human pathogens as well as life-threatening zoonotic viruses. These viruses share a common RNA replication complex, including the genomic RNA and three proteins, the nucleoprotein (N), the phosphoprotein (P), and the RNA-dependent RNA polymerase (L). During genome replication, the RNA polymerase complex first synthesizes positive-sense antigenomes, which in turn serve as template for the production of negative-sense progeny genomes. These newly synthesized antigenomic and genomic RNAs must be encapsidated by N, and the source of soluble, RNA-free N, competent for the encapsidation is a complex between N and P, named the N⁰-P complex. In this review, we summarize recent progress made in the structural characterization of the different components of this peculiar RNA polymerase machinery. We discuss common features and replication strategies and highlight idiosyncrasies encountered in different viruses, along with the key role of the dual ordered/disordered architecture of protein components and the dynamics of the viral polymerase machinery. In particular, we focus on the N⁰-P complex and its role in the nucleocapsid assembly process. These new results provide evidence that the mechanism of NC assembly is conserved between the different families and thus support a divergent evolution from a common ancestor. In addition, the successful inhibition of infection due to different NNVs by peptides derived from P suggests that the mechanism of NC assembly is a potential target for antiviral development.