Protein Nucleotidylylation in +ssRNA Viruses

Eruera, Alice-Roza; McSweeney, Alice M.; McKenzie-Goldsmith, Geena M; Ward, Vernon K.

doi:10.3390/v13081549

Cited by 7 publications

(3 citation statements)

References 166 publications

(263 reference statements)

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“…In this process, 3D pol catalyzes the covalent attachment of two uridine monophosphate (UMP) molecules to the hydroxyl group of tyrosine 3 (Y3) of VPg and generates VPg-pUpU-OH, which serves as a primer to initiate the replication process ( 82 – 84 ). This process has been extensively studied in different members of the Picornaviridae family ( 37 , 85 – 90 ), and detailed information can be found in this Review ( 90 ). Subsequently, 3D pol catalyzes the synthesis of viral negative- and positive-sense RNA within the replication complex (RC) ( 91 ).…”

Section: Roles Of 3d Pol In Picornavirus Replicationmentioning

confidence: 99%

Multiple functions of the nonstructural protein 3D in picornavirus infection

Xu,

Wang,

Cheng

et al. 2024

Front. Immunol.

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3D polymerase, also known as RNA-dependent RNA polymerase, is encoded by all known picornaviruses, and their structures are highly conserved. In the process of picornavirus replication, 3D polymerase facilitates the assembly of replication complexes and directly catalyzes the synthesis of viral RNA. The nuclear localization signal carried by picornavirus 3D polymerase, combined with its ability to interact with other viral proteins, viral RNA and cellular proteins, indicate that its noncatalytic role is equally important in viral infections. Recent studies have shown that 3D polymerase has multiple effects on host cell biological functions, including inducing cell cycle arrest, regulating host cell translation, inducing autophagy, evading immune responses, and triggering inflammasome formation. Thus, 3D polymerase would be a very valuable target for the development of antiviral therapies. This review summarizes current studies on the structure of 3D polymerase and its regulation of host cell responses, thereby improving the understanding of picornavirus-mediated pathogenesis caused by 3D polymerase.

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Section: Roles Of 3d Pol In Picornavirus Replicationmentioning

confidence: 99%

Multiple functions of the nonstructural protein 3D in picornavirus infection

Xu,

Wang,

Cheng

et al. 2024

Front. Immunol.

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“…These two studies suggested that the lack of generation of single-stranded viral RNA with an altered CRE was due to the decrease in positive-strand RNA replication, although sufficient negative-strand replication occurred for the generation of a double-stranded RF [ 114 , 115 ]. The extent to which negative-strand initiation is dependent upon the generation of uridylated VPg via the CRE-2C has yet to be resolved [ 47 , 49 , 116 ].…”

Section: A Cis-acting Replication Element (Cre-2c) Plays a Role In Lo...mentioning

confidence: 99%

Persistent Enterovirus Infection: Little Deletions, Long Infections

Chapman

2022

Vaccines

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Enteroviruses have now been shown to persist in cell cultures and in vivo by a novel mechanism involving the deletion of varying amounts of the 5′ terminal genomic region termed domain I (also known as the cloverleaf). Molecular clones of coxsackievirus B3 (CVB3) genomes with 5′ terminal deletions (TD) of varying length allow the study of these mutant populations, which are able to replicate in the complete absence of wildtype virus genomes. The study of TD enteroviruses has revealed numerous significant differences from canonical enteroviral biology. The deletions appear and become the dominant population when an enterovirus replicates in quiescent cell populations, but can also occur if one of the cis-acting replication elements of the genome (CRE-2C) is artificially mutated in the element’s stem and loop structures. This review discusses how the TD genomes arise, how they interact with the host, and their effects on host biology.

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“…Viral protein genome-linked (VPg) is a small virally-encoded protein that has multifunctional roles in specific steps of some +ssRNA viral lifecycles including viral replication and translation. VPgs are encoded in +ssRNA viral genomes including animal, plant, and fungal RNA viruses and their functions have been primarily studied in picornaviruses, caliciviruses, and potyviruses (1, 2). VPg is covalently linked to the 5’ end of the viral RNA and serves as a primer for both positive- and negative-strand RNA synthesis (3).…”

Section: Introductionmentioning

confidence: 99%

Multiple viral protein genome-linked proteins compensate viral translation in a +ssRNA virus infection

Warsaba

Stoynov

Moon

et al. 2022

Preprint

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Viral protein genome-linked (VPg) protein plays an essential role in protein-primed replication of plus stranded RNA viruses. VPg is covalently linked to the 5’ end of the viral RNA genome via a phosphodiester bond typically at a conserved amino acid. Whereas most viruses have a single VPg, some viruses encode multiple VPgs that are proposed to have redundant yet undefined roles in viral replication. Here, we use the dicistrovirus, cricket paralysis virus (CrPV), which encodes four non-identical copies of VPg, as a model to characterize the role of VPg copies in infection. Dicistroviruses encode two main open reading frames (ORFs) that are driven by distinct IRESs. We systematically generated single and combinatorial deletions and mutations of VPg1-4 within the CrPV infectious clone and monitored viral yield in Drosophila S2 cells. Deletion of one to three VPg copies progressively decreased viral yield and delayed viral replication, suggesting a threshold number of VPgs for productive infection. Mass spectrometry analysis of CrPV VPg-linked RNAs revealed viral RNA linkage to either a serine or threonine in VPg, from which mutations in all VPgs attenuated infection. Mutating serine 4 in a single VPg abolished viral infection, indicating a dominant-negative effect. Using viral minigenome reporters that monitor dicistrovirus 5’ untranslated (UTR) and intergenic internal ribosome entry site (IRES) translation revealed a relationship between VPg copy number and the ratio of distinct IRES translation. We uncover a novel viral strategy whereby VPg copies in dicistrovirus genomes compensate for the relative IRES translation efficiencies to promote infection.

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Protein Nucleotidylylation in +ssRNA Viruses

Cited by 7 publications

References 166 publications

Multiple functions of the nonstructural protein 3D in picornavirus infection

Multiple functions of the nonstructural protein 3D in picornavirus infection

Persistent Enterovirus Infection: Little Deletions, Long Infections

Multiple viral protein genome-linked proteins compensate viral translation in a +ssRNA virus infection

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