Co-folding and RNA activation of poliovirus 3Cpro polyprotein precursors

Campagnola, Grace; Peersen, Olve

doi:10.1016/j.jbc.2023.105258

Cited by 5 publications

(5 citation statements)

References 37 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HRV-14 3C binds to the stem-loop d of the cloverleaf, while HAV 3C, 3CD, and 3ABC show efficient binding to both the 5 and 3 UTR [127,152,[167][168][169][170][171]. 3ABC has a stronger binding capacity, while 3CD has a weaker RNA-binding ability [8]. In the absence of both 3C and 3CD, 3B 3 3C and 3B 123 3C serve as alternative substrates for uridylylation [172].…”

Section: Roles Of 3c(d) and Other 3c-containing Polyproteins In Picor...mentioning

confidence: 99%

“…The picornaviral virion and genome structures are highly conserved in nature. The genome consists of one open reading frame coding for a single polyprotein that can be targeted by viral proteases [3,[6][7][8]. The P1 region encodes for the capsid proteins of the virus, while the P2 and P3 portions encode the non-structural proteins (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA

Mondal,

Sarvari,

Boehr

2023

Viruses

View full text Add to dashboard Cite

The Picornaviridae family comprises a large group of non-enveloped viruses with enormous impact on human and animal health. The picornaviral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteases. The picornaviral 3C proteases share similar three-dimensional structures and play a significant role in the viral life cycle and virus–host interactions. Picornaviral 3C proteins also have conserved RNA-binding activities that contribute to the assembly of the viral RNA replication complex. The 3C protease is important for regulating the host cell response through the cleavage of critical host cell proteins, acting to selectively ‘hijack’ host factors involved in gene expression, promoting picornavirus replication, and inactivating key factors in innate immunity signaling pathways. The protease and RNA-binding activities of 3C are involved in viral polyprotein processing and the initiation of viral RNA synthesis. Most importantly, 3C modifies critical molecules in host organelles and maintains virus infection by subtly subverting host cell death through the blocking of transcription, translation, and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Here, we discuss the molecular mechanisms through which 3C mediates physiological processes involved in promoting virus infection, replication, and release.

show abstract

Section: Roles Of 3c(d) and Other 3c-containing Polyproteins In Picor...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA

Mondal,

Sarvari,

Boehr

2023

Viruses

View full text Add to dashboard Cite

show abstract

“…The 5′ UTR harbors an internal ribosomal entry site (IRES) that recruits ribosomes and other host factors and mediates cap-independent translation ( 11 , 12 ). The ORF initially encodes a single polyprotein that is co and posttranslationally cleaved by viral proteases to release the capsid proteins VP0, VP1, and VP3 and nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C, 3D), as well as some stable precursors, such as 3AB or 3CD, that are essential for the replication of viral RNA ( 13 – 15 ). Recently, a second ORF termed the upstream ORF (uORF) was identified in enteroviruses ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Multiple functions of the nonstructural protein 3D in picornavirus infection

Xu,

Wang,

Cheng

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

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.

show abstract

“…The genome of PV encodes a single large 2 polyprotein (about 2,200 amino acid[aa] residues) that is subsequently processed into each viral protein, and a small protein derived from an upstream open reading frame (uORF) (2). The polyprotein is initially processed into three precursor proteins, P1 (coding VP4VP2VP3VP1), P2 (coding 2A2B2C), and P3 (coding 3A3B3C3D), by viral proteases (2A pro and 3C pro /3CD pro /3ABC pro ) (3)(4)(5). Subsequently, P1 is processed into viral capsid proteins (VP4VP2[VP0], VP3, VP1), P2 is processed into proteins that have roles in viral RNA synthesis and also in virion production/release (2A pro protease, 2B viroporin, 2C ATPase/hel ATPase/helicase) (3,(6)(7)(8)(9)(10), and P3 is processed into proteins that most directly serve for RNA synthesis (3A [unknown enzymatic function / recruitment of host proteins GBF1/ACBD3/PI4KB], 3B [also known as VPg, the primer for RNA synthesis], 3C pro proteases, 3D pol polymerase) (1,(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

An Efficient Trans Complementation System for In Vivo Replication of Defective Poliovirus Mutants

Arita

2024

Preprint

View full text Add to dashboard Cite

The picornavirus genome encodes a large single polyprotein that is processed by viral proteases to form an active replication complex. The replication complex is formed with the viral genome, host proteins, and viral proteins that are produced/translated directly from each of the viral genomes (cis-provided viral proteins). Efficient complementation in vivo of replication complex formation by trans-provided viral proteins, thus exogenous or ectopically expressed viral proteins, remains to be demonstrated. Here we report an efficient trans-complementation system for the replication of defective poliovirus (PV) mutants by a viral polyprotein precursor in HEK 293 cells. Viral 3AB in the polyprotein, but not 2BC, was processed exclusively in cis. Replication of a defective PV replicon mutant, with a disrupted cleavage site for viral 3Cpro protease between 3Cpro and 3Dpol (3C/D[A/G] mutant) could be rescued by a trans-provided viral polyprotein. Only a defect of 3Dpol activity, of the replicon could be rescued in trans; inactivating mutations in 2CATPase/hel, 3B, and 3Cpro of the replicon completely abrogated the trans-rescued replication. An intact N-terminus of the 3Cpro moiety, of the trans-provided 3CDpro, was essential for the trans-rescue activity. By using this trans-complementation system, a high-titer defective PV pseudovirus (> 107 infectious units per mL) could be produced with the defective mutants, whose replication was completely dependent on trans-complementation. This work reveals potential roles of exogenous viral proteins in PV replication and offers insights into protein/protein and protein/RNA interactions during picornavirus infection.

show abstract

Co-folding and RNA activation of poliovirus 3Cpro polyprotein precursors

Cited by 5 publications

References 37 publications

Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA

Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA

Multiple functions of the nonstructural protein 3D in picornavirus infection

An Efficient Trans Complementation System for In Vivo Replication of Defective Poliovirus Mutants

Contact Info

Product

Resources

About