scholarly journals Foot-and-Mouth Disease Virus Counteracts on Internal Ribosome Entry Site Suppression by G3BP1 and Inhibits G3BP1-Mediated Stress Granule Assembly via Post-Translational Mechanisms

2018 ◽  
Vol 9 ◽  
Author(s):  
Xu Ye ◽  
Ting Pan ◽  
Dang Wang ◽  
Liurong Fang ◽  
Jun Ma ◽  
...  
Keyword(s):  
Disease Virus ◽  
Internal Ribosome Entry Site ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Stress Granule ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Translational Mechanisms

scholarly journals Identification and Characterization of a cis-Acting Replication Element (cre) Adjacent to the Internal Ribosome Entry Site of Foot-and-Mouth Disease Virus

2002 ◽  
Vol 76 (19) ◽  
pp. 9686-9694 ◽  
Author(s):  
Peter W. Mason ◽  
Svetlana V. Bezborodova ◽  
Tina M. Henry
Keyword(s):  
Disease Virus ◽  
Internal Ribosome Entry Site ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Wild Type ◽  
Coding Region ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Over the last few years, an essential RNA structure known as the cis-acting replicative element (cre) has been identified within the protein-coding region of several picornaviruses. The cre, a stem-loop structure containing a conserved AAACA motif, functions as a template for addition of U residues to the protein primer 3B. By surveying the genomes of representatives of several serotypes of foot-and-mouth disease virus (FMDV), we discovered a putative cre in the 5′ untranslated region of the genome (contiguous with the internal ribosome entry site [IRES]). To confirm the role of this putative cre in replication, we tested the importance of the AAACA motif and base pairing in the stem in FMDV genome replication. To this end, cre mutations were cloned into an FMDV replicon and into synthetic viral genomes. Analyses of the properties of these replicons and genomes revealed the following. (i) Mutations in the AAACA motif severely reduced replication, and all viruses recovered from genomes containing mutated AAACA sequences had reverted to the wild-type sequence. (ii) Mutations in the stem region showed that the ability to form this base-paired structure was important for replication. Although the cre was contiguous with the IRES, the mutations we created did not significantly reduce IRES-mediated translation in vivo. Finally, the position of the cre at the 5′ end of the genome was shown not to be critical for replication, since functional replicons and viruses lacking the 5′ cre could be obtained if a wild-type cre was added to the genome following the 3Dpol coding region. Taken together, these results support the importance of the cre in replication and demonstrate that the activity of this essential element does not require localization within the polyprotein-encoding region of the genome.

scholarly journals Sequence and secondary structure requirements in a highly conserved element for foot-and-mouth disease virus internal ribosome entry site activity and eIF4G binding

2004 ◽  
Vol 85 (9) ◽  
pp. 2555-2565 ◽  
Author(s):  
Gergis Bassili ◽  
Eleni Tzima ◽  
Yutong Song ◽  
Lanja Saleh ◽  
Kerstin Ochs ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Disease Virus ◽  
Internal Ribosome Entry Site ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Primary Sequence ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) and other picornaviruses initiate translation of their positive-strand RNA genomes at the highly structured internal ribosome entry site (IRES), which mediates ribosome recruitment to an internal site of the virus RNA. This process is facilitated by eukaryotic translation initiation factors (eIFs), such as eIF4G and eIF4B. In the eIF4G-binding site, a characteristic, discontinuous sequence element is highly conserved within the cardio- and aphthovirus subgroup (including FMDV) of the picornaviruses. This conserved element was mutated in order to investigate its primary sequence and secondary structure requirements for IRES function. Both binding of eIF4G to the IRES and IRES-directed translation are seriously impaired by mutations in two unpaired dinucleotide stretches that are exposed from the double-stranded (ds)RNA. In the base-paired regions of the conserved element, maintenance of the double-stranded secondary structure is essential, whilst in some cases, the primary sequence within the dsRNA regions is also important for IRES function. Extra eIF4F added to the translation reaction does not restore full IRES activity or eIF4G binding, indicating that disturbances in the structure of this conserved element cannot be overcome by increased initiation factor concentrations.

scholarly journals The RNA pseudoknots in foot-and-mouth disease virus are dispensable for genome replication but essential for the production of infectious virus

2020 ◽  
Author(s):  
Joseph C. Ward ◽  
Lidia Lasecka-Dykes ◽  
Chris Neil ◽  
Oluwapelumi Adeyemi ◽  
Sarah Gold ◽  
...  
Keyword(s):  
Disease Virus ◽  
Infectious Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Genome Replication ◽  
Entry Site ◽  
Stem Loop ◽  
Initiation Of Translation ◽  
Mouth Disease Virus ◽  
Foot And Mouth

AbstractThe positive stranded RNA genomes of picornaviruses comprise a single large open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). Foot-and-mouth disease virus (FMDV) has an unusually large 5′ UTR (1.3 kb) containing five structural domains. These include the internal ribosome entry site (IRES), which facilitates initiation of translation, and the cis-acting replication element (cre). Less well characterised structures are a 5′ terminal 360 nucleotide stem-loop, a variable length poly-C-tract of approximately 100-200 nucleotides and a series of two to four tandemly repeated pseudoknots (PKs). We investigated the structures of the PKs by selective 2′ hydroxyl acetylation analysed by primer extension (SHAPE) analysis and determined their contribution to genome replication by mutation and deletion experiments. SHAPE and mutation experiments confirmed the importance of the previously predicted PK structures for their function. Deletion experiments showed that although PKs are not essential for replication, they provide genomes with a competitive advantage. However, although replicons and full-length genomes lacking all PKs were replication competent, no infectious virus was rescued from genomes containing less than one PK copy. This is consistent with our earlier report describing the presence of putative packaging signals in the PK region.

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