This article is about the protein and gene. For the Vehicle Production Group, seeMV-1. For other uses, seeVPG.
VPg (viral protein genome-linked) is a protein that iscovalently attached to the 5′ end of positive strand viralRNA and acts as aprimer duringRNA synthesis in a variety of virus families includingPicornaviridae,Potyviridae,Astroviridae andCaliciviridae. There are some studies showing that a possible VPg protein is also present inastroviridae, however, experimentalevidence for this has not yet been provided and requires further study.[1] The primer activity of VPg occurs when the protein becomes uridylated, providing a freehydroxyl that can be extended by the virally encodedRNA-dependent RNA polymerase. For some virus families, VPg also has a role in translation initiation by acting like a 5'mRNA cap.
VPg was first described in initial investigations ofpoliovirus RNA as a protein covalently attached to the 5' end of the genome.[2][3] and later seen in caliciviruses.[4]
VPg must undergo post-translational uridylylation before it can act as a primer for replication. 3Dpol (the RdRp) is able to synthesize VPg-pUpU-OH by using a polyA sequence within a stem-loop structure (cis-acting replication element) of 2C-ATPase as a template.[5][6][7] Furthermore, a 5' terminal cloverleaf is required in cis to form the 3Dpol preinitiation RNA replication complex involved in uridylylating VPg.[8]
3CDpro (aprotease) cleaves VPg from membrane-bound 3AB.
Studies that usedproteinase K to cleave VPg from the viral genome discovered that calicivirus vesicular exanthema virus lacking VPg is no longer infectious[9] whereas poliovirus retains infectivity even with the absence of VPg.[10] Because VPg sits at the 5' end of the genome, similar to eukaryotic5' mRNA caps, several experiments were performed to explore its function in translation. Poliovirus utilizes aninternal ribosome entry site (IRES) instead of a cap for translation initiation, abrogating the requirement of VPg in initial infection[11] whereas studies with feline calicivirus confirmed that the VPg protein interacts directly with the cap-binding protein of theribosome, eIF4E, and that this interaction is essential for viral translation.[12]
^Flanegan JB, Petterson RF, Ambros V, Hewlett MJ, Baltimore D. Covalent linkage of a protein to a defined nucleotide sequence at the 5′-terminus of virion and replicative intermediate rnas of poliovirus. Proc Natl Acad Sci U SA. 1977;74:961–965.
^Lee YF, Nomoto A, Detjen BM, Wimmer E. The genome-linked protein of picornaviruses i. A protein covalently linked to poliovirus genome rna. Proc Natl Acad Sci U S A. 1977;74:59–63.
^Schaffer FL, Ehresmann DW, Fretz MK, Soergel MI. A protein, vpg, covalently linked to 36s calicivirus rna. J Gen Virol. 1980;47(1):215–220.
^Goodfellow I, Chaudhry Y, Richardson A, Meredith J, Almond J W, Barclay W, Evans D J. Identification of a cis-acting replication element within the poliovirus coding region. J Virol. 2000;74:4590–4600.
^Paul A V, Rieder E, Kim D W, van Boom J H, Wimmer E. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J Virol. 2000;74:10359–10370.
^Rieder E, Paul A V, Kim D W, van Boom J H, Wimmer E. Genetic and biochemical studies of poliovirus cis-acting replication element cre in relation to VPg uridylylation. J Virol. 2000;74:10371–10380.
^Lyons T, Murray KE, Roberts AW, Barton DJ. Poliovirus 5′-terminal cloverleaf RNA is required in cis for VPg uridylylation and the initiation of negative-strand RNA synthesis. J Virol. 2001;75(22):10696–708.
^Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus rna. J Gen Virol. 1978;41(2):443–446.
^Van der Werf S, Bradley J, Wimmer E, Studier FW, Dunn JJ. Synthesis of infectious poliovirus rna by purified t7 rna polymerase. Proc Natl Acad Sci. 1986;83:2330–2334.
^Fitzgerald KD, Semler BL. Bridging ires elements in mrnas to the eukaryotic translation apparatus. Biochim Biophys Acta. 2009;1789(9-10):518–528.
^Goodfellow I, Chaudhry Y, Gioldasi I, Gerondopoulos A, Natoni A, Labrie L, Laliberte JF, Roberts L. Calicivirus translation initiation requires an interaction between vpg and eif 4 e. EMBO Rep. 2005;6(10):968–972.
