The control of paramyxovirus genome hexamer length and mRNA editing

Abstract

The unusual ability of a human parainfluenza virus type 2 (hPIV2) nucleoprotein point mutation (NP) to strongly enhance minigenome replication was found to depend on the absence of a functional, internal element of the bipartite replication promoter (CRII). This point mutation allows relatively robust CRII-minus minigenome replication in a CRII-independent manner, under conditions in which NP is essentially inactive. The nature of the amino acid at position 202 apparently controls whether viral RNA-dependent RNA polymerase (vRdRp) can, or cannot, initiate RNA synthesis in a CRII-independent manner. By repressing genome synthesis when vRdRp cannot correctly interact with CRII, gln of N, the only residue of the RNA-binding groove that contacts a nucleotide base in the N-RNA, acts as a gatekeeper for wild-type (CRII-dependent) RNA synthesis. This ensures that only hexamer-length genomes are replicated, and that the critical hexamer phase of the -acting mRNA editing sequence is maintained.

The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector

“…Like the genomes of other paramyxoviruses, SeV usually includes six genes, which encode six major proteins. The low rate of homologous RNA recombination in paramyxoviruses genomes probably results from the unusual genomic requirement for polyhexameric length (6n+0) [83]. Therefore, SeV infection provides a stable foreign gene expression system.…”

“…Like all other representatives of the Paramyxoviradae family and negative sense RNA viruses, SeV is genetically stable and evolves very slowly [ 80 ]. It belongs to a category of viruses that are governed by the “rule of six” [ 81 – 83 ]. Like the genomes of other paramyxoviruses, SeV usually includes six genes, which encode six major proteins.…”

The Nucleoprotein and Phosphoprotein of Measles Virus

“…With the help of NCs formed in vitro , we can identify both the binding of the 5′ end of the RNA to the first N protomer of the NCs, and the binding of the 3′ end on the final protomer of the NCs (Figure 5B): The lower part of N is still bound to the RNA but the upper part of N does not cover the terminal bases and only residue Q202 in the lower edge of the groove binds the last base at the 3′ end. Q202 is important for replication initiation in PIV2 because the mutant Q202A shows increased replication (Matsumoto et al, 2017, 2018). The fact that the 3′ end of the RNA is rather “open” may help the binding of L at the 3′ end of the vRNA.…”

Bipartite promoters and RNA editing of paramyxoviruses and filoviruses

“…le Mercier and Kolakofsky displaced. PE1 of N wt -RNA was found to contain a negative element, which when mutated (e.g., N Q202A ) allows robust PE2-independent RNA synthesis that is now also largely independent of overall genome length, that is, a strict rule of six no longer applies (Matsumoto et al 2017(Matsumoto et al , 2018. PE2 in N wt -RNAs is apparently needed to neutralize the negative effects of PE1, ensuring that the conserved hexamer alignment of the PE2 tripartite repeat is critical for the initiation of RNA synthesis.…”