VPg (viral protein genome-linked) is a protein that is
covalent
A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
ly attached to the 5′ end of positive strand viral
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
and acts as a
primer
Primer may refer to:
Arts, entertainment, and media Films
* ''Primer'' (film), a 2004 feature film written and directed by Shane Carruth
* ''Primer'' (video), a documentary about the funk band Living Colour
Literature
* Primer (textbook), a t ...
during
RNA synthesis
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
in a variety of virus families including
Picornaviridae
Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm i ...
,
Potyviridae
''Potyviridae'' is a family of positive-strand RNA viruses that encompasses more than 30% of known plant viruses, many of which are of great agricultural significance. The family has 12 genera and 235 species, three of which are unassigned to a ...
and
Caliciviridae
The ''Caliciviridae'' are a family of "small round structured" viruses, members of Class IV of the Baltimore scheme. Caliciviridae bear resemblance to enlarged picornavirus and was formerly a separate genus within the picornaviridae. They are p ...
. There are some studies showing that a possible VPg protein is also present in
astroviridae
''Astroviridae'' is a family of non-enveloped ssRNA viruses that cause infections in different animals. The family name is derived from the Greek word ''astron'' ("star") referring to the star-like appearance of spikes projecting from the surface ...
, however, experimental
evidence
Evidence for a proposition is what supports this proposition. It is usually understood as an indication that the supported proposition is true. What role evidence plays and how it is conceived varies from field to field.
In epistemology, evidenc ...
for this has not yet been provided and requires further study.
[ ]The primer activity of VPg occurs when the protein becomes uridylated, providing a free
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
that can be extended by the virally encoded
RNA-dependent RNA polymerase
RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t ...
. For some virus families, VPg also has a role in translation initiation by acting like a 5'
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
cap.
VPg was first described in initial investigations of
poliovirus
A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3.
Poliovirus is composed of an ...
RNA as a protein covalently attached to the 5' end of the genome.
[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.] and later seen in caliciviruses.
[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.]
Attachment during RNA synthesis
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 ''Cis-acting replication elements'' bring together the 5′ and 3′ ends during replication of positive-sense single-stranded RNA viruses (for example Picornavirus, Flavivirus, coronavirus, togaviruses, Hepatitis C virus) and double-stranded RNA vi ...
) of 2C-ATPase as a template.
[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.] Furthermore, a 5' terminal cloverleaf is required in cis to form the 3Dpol preinitiation RNA replication complex involved in uridylylating VPg.
[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.]
3CDpro (a
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
) cleaves VPg from membrane-bound 3AB.
Function as a 5' cap
Studies that used
proteinase K
In molecular biology Proteinase K (, ''protease K'', ''endopeptidase K'', ''Tritirachium alkaline proteinase'', ''Tritirachium album serine proteinase'', ''Tritirachium album proteinase K'') is a broad-spectrum serine protease. The enzyme was dis ...
to cleave VPg from the viral genome discovered that calicivirus vesicular exanthema virus lacking VPg is no longer infectious
[Burroughs JN, Brown F. Presence of a covalently linked protein on calicivirus rna. J Gen Virol. 1978;41(2):443–446.] whereas poliovirus retains infectivity even with the absence of VPg.
[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.] Because VPg sits at the 5' end of the genome, similar to eukaryotic
5' mRNA caps, several experiments were performed to explore its function in translation. Poliovirus utilizes an
internal ribosome entry site An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at t ...
(IRES) instead of a cap for translation initiation, abrogating the requirement of VPg in initial infection
[Fitzgerald KD, Semler BL. Bridging ires elements in mrnas to the eukaryotic translation apparatus. Biochim Biophys Acta. 2009;1789(9-10):518–528.] whereas studies with feline calicivirus confirmed that the VPg protein interacts directly with the cap-binding protein of the
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
, eIF4E, and that this interaction is essential for viral translation.
[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.]
Sources
''Principles of Virology'' by S.J. Flint, L.W. Enquist, V.R. Racaniello, A.M. Skalka ()
{{DEFAULTSORT:Vpg
Viral nonstructural proteins