Initiation of protein-primed picornavirus RNA synthesis

Abstract

Plus strand RNA viruses use different mechanisms to initiate the synthesis of their RNA chains. The Picornaviridae family constitutes a large group of plus strand RNA viruses that possess a small terminal protein (VPg) covalently linked to the 5’-end of their genomes. The RNA polymerases of these viruses use VPg as primer for both minus and plus strand RNA synthesis. In the first step of the initiation reaction the RNA polymerase links a UMP to the hydroxyl group of a tyrosine in VPg using as template a cis-replicating element (cre) positioned in different regions of the viral genome. In this review we will summarize what is known about the intiation reaction of protein-primed RNA synthesis by the RNA polymerases of the Picornaviridae. As an example we will use the RNA polymerase of poliovirus, the prototype of Picornaviridae. We will also discuss models of how these nucleotidylylated protein primers might be used, together with viral and cellular replication proteins and other cis-replicating RNA elements, during minus and plus strand RNA synthesis.

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

“…Our results suggest that the Sabin 2 5′UTR is incompatible with the P2 region of EV-C 99–68229. This incompatibility may be due to intra- or intermolecular interactions during replication, because the 2 C region contains the cis -acting replication element ( cre ), a 61 nt-long sequence involved in initiating the synthesis of negative and positive genomic strands through VPg uridylation2. However, the 26 nt-long minimal cre sequences present in the genomes of the two viruses are identical (see Supplementary Fig.…”

“…This genome consists of two untranslated regions (5′UTR and 3′UTR) flanking a single large open reading frame. The 5′UTR and 3′UTR contain secondary structures involved in initiating the translation and replication of the genome234. The open reading frame is translated into a single polyprotein that is proteolytically processed to yield the four capsid proteins (VP1–4), which are encoded by the P1 region of the genome, and the non-structural proteins, encoded by the P2 and P3 regions.…”

A novel passerivirus (family Picornaviridae) in an outbreak of enteritis with high mortality in estrildid finches (Uraeginthus sp.)

“…The nucleotide sequence motif AAAC/G forms the cis-acting replication element (CRE) [7,15] and is presumed to be active when present in the apical loop of the secondary structure [4,6,7,15]. Based on RNA secondary structure prediction, the thermodynamically most favoured site (A1338AACG or A1346AACA in the loop of the structure with ΔG = -21.1 kcal/mol) of CRE motifs is located between nt 1338 and 1342 or nt 1346 and 1350 in the L protein coding region (Fig.…”

Domain I of the 5′ non-translated genomic region in coxsackievirus B3 RNA is not required for productive replication

“…As domain I is one of 4 characterized cis-acting replication elements [CRE; (Paul and Wimmer, 2015)] which aid enteroviral replicational efficiency, we were curious to determine whether larger deletions of domain I were lethal, thus accounting for failing to detect them. We experimentally deleted nucleotides 1-77 from an infectious cDNA copy of a CVB3 genome (Tracy et al, 2002), thereby excising domain I through stem-loop d. This construct, CVB3-TD78, was viable and produced infectious progeny virus.…”