Effects of temperature on viral RNA synthesis and RNA polymerase activity in a foot-and-mouth disease virus system

1970 ◽  
Vol 32 (4) ◽  
pp. 318-328 ◽  
Author(s):  
J. -F. Delagneau
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Rna Synthesis ◽  
Foot And Mouth Disease ◽  
Polymerase Activity ◽  
Viral Rna ◽  
Mouth Disease Virus ◽  
Rna Polymerase Activity ◽  
Effects Of Temperature ◽  
Virus System

scholarly journals Factors Required for the Uridylylation of the Foot-and-Mouth Disease Virus 3B1, 3B2, and 3B3 Peptides by the RNA-Dependent RNA Polymerase (3Dpol) In Vitro

2005 ◽  
Vol 79 (12) ◽  
pp. 7698-7706 ◽  
Author(s):  
Arabinda Nayak ◽  
Ian G. Goodfellow ◽  
Graham J. Belsham
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Rna Synthesis ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coding Region ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Positive Strand Rna

ABSTRACT The 5′ terminus of picornavirus genomic RNA is covalently linked to the virus-encoded peptide 3B (VPg). Foot-and-mouth disease virus (FMDV) is unique in encoding and using 3 distinct forms of this peptide. These peptides each act as primers for RNA synthesis by the virus-encoded RNA polymerase 3Dpol. To act as the primer for positive-strand RNA synthesis, the 3B peptides have to be uridylylated to form VPgpU(pU). For certain picornaviruses, it has been shown that this reaction is achieved by the 3Dpol in the presence of the 3CD precursor plus an internal RNA sequence termed a cis-acting replication element (cre). The FMDV cre has been identified previously to be within the 5′ untranslated region, whereas all other picornavirus cre structures are within the viral coding region. The requirements for the in vitro uridylylation of each of the FMDV 3B peptides has now been determined, and the role of the FMDV cre (also known as the 3B-uridylylation site, or bus) in this reaction has been analyzed. The poly(A) tail does not act as a significant template for FMDV 3B uridylylation.

scholarly journals (F)uridylylated Peptides Linked to VPg1 of Foot-and- Mouth Disease Virus (FMDV): Design, Synthesis and X-Ray Crystallography of the Complexes with FMDV RNA-Dependent RNA Polymerase

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2360 ◽  
Author(s):  
Sonia de Castro ◽  
Cristina Ferrer-Orta ◽  
Alberto Mills ◽  
Gloria Fernández-Cureses ◽  
Federico Gago ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Viral Rna ◽  
Hydroxyl Group ◽  
Rna Dependent Rna Polymerase ◽  
X Ray ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) is an RNA virus belonging to the Picornaviridae family that contains three small viral proteins (VPgs), named VPg1, VPg2 and VPg3, linked to the 5′-end of the viral genome. These VPg proteins act as primers for RNA replication, which is initiated by the consecutive binding of two UMP molecules to the hydroxyl group of Tyr3 in VPg. This process, termed uridylylation, is catalyzed by the viral RNA-dependent RNA polymerase named 3Dpol. 5-Fluorouridine triphosphate (FUTP) is a potent competitive inhibitor of VPg uridylylation. Peptide analysis showed FUMP covalently linked to the Tyr3 of VPg. This fluorouridylylation prevents further incorporation of the second UMP residue. The molecular basis of how the incorporated FUMP blocks the incorporation of the second UMP is still unknown. To investigate the mechanism of inhibition of VPg uridylylation by FUMP, we have prepared a simplified 15-mer model of VPg1 containing FUMP and studied its x-ray crystal structure in complex with 3Dpol. Unfortunately, the fluorouridylylated VPg1 was disordered and not visible in the electron density maps; however, the structure of 3Dpol in the presence of VPg1-FUMP showed an 8 Å movement of the β9-α11 loop of the polymerase towards the active site cavity relative to the complex of 3Dpol with VPg1-UMP. The conformational rearrangement of this loop preceding the 3Dpol B motif seems to block the access of the template nucleotide to the catalytic cavity. This result may be useful in the design of new antivirals against not only FMDV but also other picornaviruses, since all members of this family require the uridylylation of their VPg proteins to initiate the viral RNA synthesis.

scholarly journals Effect of actinomycin D and guanidine on the formation of a ribonucleic acid polymerase induced by foot-and-mouth-disease virus and on the replication of virus and viral ribonucleic acid

1969 ◽  
Vol 112 (3) ◽  
pp. 317-323 ◽  
Author(s):  
D. N. Black ◽  
F. Brown
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Ribonucleic Acid ◽  
Actinomycin D ◽  
Foot And Mouth Disease ◽  
Growth Cycle ◽  
Mouth Disease ◽  
Viral Rna ◽  
Mouth Disease Virus ◽  
Foot And Mouth

The RNA-dependent RNA polymerase induced in baby-hamster kidney cells by infection with foot-and-mouth-disease virus can be detected as early as 60min. after infection, which is 60min. before viral RNA synthesis commences. The time at which the polymerase can first be detected coincides with the latest time at which actinomycin D (50μg./107 cells) or guanidine (1mg./107 cells) inhibits virus replication. However, by increasing the concentration of guanidine, viral replication can be inhibited later in the growth cycle, casting doubt on the validity of the hypothesis that guanidine acts specifically on the formation of the viral RNA polymerase.

scholarly journals BothcisandtransActivities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

2016 ◽  
Vol 90 (15) ◽  
pp. 6864-6883 ◽  
Author(s):  
Morgan R. Herod ◽  
Cristina Ferrer-Orta ◽  
Eleni-Anna Loundras ◽  
Joseph C. Ward ◽  
Nuria Verdaguer ◽  
...  
Keyword(s):  
Disease Virus ◽  
Viral Genome ◽  
Foot And Mouth Disease ◽  
Rna Replication ◽  
Mouth Disease ◽  
Viral Rna ◽  
Genome Replication ◽  
Replication Complex ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACTThePicornaviridaeis a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided intrans(i.e., via expression from a separate RNA molecule), while others are required incis(i.e., expressed from the template RNA molecule).In vitrostudies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymaticcis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that thiscis-acting role of 3D is distinct from the catalytic activity, which is predominantlytransacting. Immunofluorescence studies suggest that bothcis- andtrans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts inciswith RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further.IMPORTANCEFoot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., intrans) while others must originate from the template (i.e., incis). Here, we present an analysis ofcisandtransactivities of the RNA-dependent RNA polymerase 3D. We demonstrate a novelcis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen.

scholarly journals RNA Polymerase Activity Assay on Biochips: Correlation between Template DNA Density and RNA Synthesis

2010 ◽  
Vol 31 (7) ◽  
pp. 2107-2109 ◽  
Author(s):  
Bok-Hui Lee ◽  
Hyun-Jung Seo ◽  
So-Hyun Kim ◽  
Woong Jung ◽  
Dong-Woon Kim ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Synthesis ◽  
Polymerase Activity ◽  
Activity Assay ◽  
Rna Polymerase Activity ◽  
Template Dna ◽  
Dna Density

scholarly journals Structure of Foot-and-Mouth Disease Virus RNA-dependent RNA Polymerase and Its Complex with a Template-Primer RNA

2004 ◽  
Vol 279 (45) ◽  
pp. 47212-47221 ◽  
Author(s):  
Cristina Ferrer-Orta ◽  
Armando Arias ◽  
Rosa Perez-Luque ◽  
Cristina Escarmís ◽  
Esteban Domingo ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Rna Dependent Rna Polymerase ◽  
Virus Rna ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Primer Rna
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