Internal ribosomal entry site-mediated translation initiation in equine rhinitis A virus: similarities to and differences from that of foot-and-mouth disease virus.
Abstract: Equine rhinitis A virus (ERAV) has recently been classified as an aphthovirus, a genus otherwise comprised of the different serotypes of Foot-and-mouth disease virus (FMDV). FMDV initiates translation via a type II internal ribosomal entry site (IRES) and utilizes two in-frame AUG codons to produce the leader proteinases Lab and Lb. Here we show that the ERAV 5' nontranslated region also possesses the core structures of a type II IRES. The functional activity of this region was characterized by transfection of bicistronic plasmids into BHK-21 cells. In this system the core type II structures, stem-loops D to L, in addition to a stem-loop (termed M) downstream of the first putative initiation codon, are required for translation of the second reporter gene. In FMDV, translation of Lb is more efficient than that of Lab despite the downstream location of the Lb AUG codon. The ERAV genome also has putative initiation sites in positions similar to those utilized in FMDV, except that in ERAV these are present as two AUG pairs (AUGAUG). Using the bicistronic expression system, we detected initiation from both AUG pairs, although in contrast to FMDV, the first site is strongly favored over the second. Mutational analysis of the AUG codons indicated that AUG2 is the major initiation site, although AUG1 can be accessed, albeit inefficiently, in the absence of AUG2. Further mutational analysis indicated that codons downstream of AUG2 appear to be accessed by a mechanism other than leaky scanning. Furthermore, we present preliminary evidence that it is possible for ribosomes to access downstream of the two AUG pairs. This study reveals important differences in IRES function between aphthoviruses.
Publication Date: 2000-11-23 PubMed ID: 11090170PubMed Central: PMC112453DOI: 10.1128/jvi.74.24.11708-11716.2000Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examined how the Equine rhinitis A virus (ERAV) starts protein production, noting similarities and differences with the Foot-and-mouth disease virus (FMDV). It revealed that ERAV’s method of starting protein production requires certain structures, has two potential start points, and functions differently compared to FMDV.
Introduction and Objective
- The main purpose of this study was to explore how the Equine rhinitis A virus (ERAV) begins protein synthesis, a process known as translation initiation. The researchers drew comparisons and highlighted differences with a similar virus, Foot-and-mouth disease virus (FMDV).
- ERAV was recently classified into the genus aphthovirus, which previously only included the different serotypes of FMDV, prompting a closer look at their similarities and differences.
Methodology
- The researchers used a lab technique involving the transfection of bicistronic plasmids into BHK-21 cells to study ERAV’s translation initiation.
- This study involved the analysis of a region of ERAV’s genome and the identification of core structures associated with a type II internal ribosomal entry site (IRES) that are crucial for translation initiation.
- The researchers also looked into initiation sites inside ERAV’s genome that are similar to the ones used in FMDV, more specifically, the two AUG pairs (AUG sequences are recognized by the translation initiation system as the start codon).
Key Findings
- ERAV was found to possess the core structures of a type II IRES, similar to FMDV. However, its translation initiation requires these structures, along with a specific stem-loop structure, to successfully produce proteins.
- Two putative initiation sites were detected in ERAV, represented by two AUG pairs, suggesting there are two potential starting points for protein production. However, unlike FMDV, ERAV strongly favors the first site over the second.
- Further analysis revealed that in relation to the AUG codons, AUG2 was observed as the more preferred initiation site, though the lesser preferred AUG1 could also be accessed, albeit less efficiently.
- The researchers found evidence suggesting that the ribosomes could access areas downstream of the two AUG pairs, implying potential variations in protein translation patterns.
Conclusion
- The study concludes by asserting that, despite ERAV and FMDV being in the same genus, there are marked differences in their IRES function, highlighting the complexity and variations in translation initiation among similar virus types.
Cite This Article
APA
Hinton TM, Li F, Crabb BS.
(2000).
Internal ribosomal entry site-mediated translation initiation in equine rhinitis A virus: similarities to and differences from that of foot-and-mouth disease virus.
J Virol, 74(24), 11708-11716.
https://doi.org/10.1128/jvi.74.24.11708-11716.2000 Publication
Researcher Affiliations
- Department of Microbiology and Immunology and the CRC for Vaccine Technology, The University of Melbourne, Parkville, Victoria 3010, Australia.
MeSH Terms
- Amino Acid Sequence
- Animals
- Aphthovirus / physiology
- Foot-and-Mouth Disease / virology
- Molecular Sequence Data
- Picornaviridae / physiology
- Picornaviridae Infections / virology
- Protein Biosynthesis
- Ribosomes
- Virus Replication
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