# Sequences and Structures of Viral Proteins Linked to the Genomes (VPg) of RNA Viruses

## TL;DR

This paper reviews the structure and function of VPg proteins linked to RNA virus genomes, highlighting conserved motifs and their roles in viral replication.

## Contribution

The paper identifies conserved motifs and structural patterns in VPg proteins across diverse RNA viruses using mutagenesis and HMM analysis.

## Key findings

- A conserved 5 amino acid motif at the N-termini of picornaviral VPgs is crucial for covalent bonding to RNA.
- VPgs in picornaviruses, dicistroviruses, and comoviruses bind RNA through tyrosine, serine, or threonine residues.
- Lysine and positively charged residues in VPgs may facilitate interactions with RNA and host factors.

## Abstract

In the mid-1970s, it was revealed that the 5′ end of the RNA genome of poliovirus (PV) was covalently linked to a peptide called VPg (viral protein, genome-linked). Subsequently, VPgs have been found attached to many other viruses and even phages. This review summarizes the patterns of physicochemical properties that are conserved within the VPgs of plus-strand RNA viruses where short-peptide VPgs have been identified. Mutagenesis and structural data indicate the importance of a 5 aa conserved motif at the N-termini of picornaviral VPgs (around the tyrosine 3 residue, which forms a covalent bond to UMP and the RNA). Hidden Markov models have been used to find motifs and VPgs in additional genera of picornaviruses, as well as dicistroviruses in insects and comoviruses in plants. These latter VPgs are bound to the RNA termina through linkages to serine or threonine. The role of free VPg and VPgpU needs clarification, especially in light of multiple genome copies in many of the viruses. Lysine and other positively charged side chains are hallmarks of VPgs. These may contribute to interactions with the viral RNA, polymerase, membranes and cellular proteins. The larger protein VPgs from potyviruses and noroviruses/caliciviruses may also show some areas of similar properties to these small peptides.