Potential secondary and tertiary structure in the genomic RNA of foot and mouth disease virus

Clarke, Berwyn; Brown, Aaron; Currey, Kathleen M.; Newton, Susan E; Rowlands, David J.; Carroll, Anthony R.

doi:10.1093/nar/15.17.7067

Cited by 85 publications

(69 citation statements)

References 31 publications

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“…These domains in the polioviruses correspond to sequences beginning at BeAn nucleotides 792 and 849, an area that is in the center of the translation enhancing region for cardioviruses and aphthoviruses (46). The primary and secondary structure of the cardioviruses (including the TMEV) and the aphthoviruses in this location is highly conserved (47,48). Whether the attenuating effect observed in TMEV chimera 2 is due to a relative block in translation in neocortical neurons remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Genomic regions of neurovirulence and attenuation in Theiler murine encephalomyelitis virus.

Calenoff

Faaberg

Lipton

1990

Proc. Natl. Acad. Sci. U.S.A.

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Full-length cDNA clones of two Theiler murine encephalomyelitis virus (TMEV) strains, one highly virulent and the other less virulent, were constructed in the bacterial plasmid pGEMR-3. Transfection of BHK-21 cells with RNA transcribed from these cDNAs yielded progeny viruses with the exact in vitro growth phenotype and mouse neurovirulence pattern of the respective parental virus strains. RNA transcripts derived from recombinant chimeras constructed by exchanging corresponding genomic regions [5' noncoding, leader/P1 (L/P1), P2, P3, and 3' noncoding] between the parental cDNAs were infectious and enabled analysis of the growth characteristics in vitro and mouse neurovirulence of the chimeras. A correlation was found between plaque size and temperature sensitivity and the origin of the L/P1 region. Neurovirulence mapped primarily to the L/P1 region encoding the leader and coat proteins. Depending on parental origin, the 5' noncoding region either influenced virus attenuation or augmented virulence.Theiler murine encephalomyelitis viruses (TMEVs) are naturally occurring enteric pathogens of mice. They constitute a separate serological group within the picornavirus family (1), and, based on the complete nucleotide sequence and genome organization, TMEVs have been unofficially classified as cardioviruses, along with encephalomyocarditis virus and Mengo virus (2, 3). TMEVs can be divided into two groups on the basis of their growth characteristics in vitro and neurovirulence after intracerebral (i.c.) inoculation (4, 5). The first group consists oftwo highly virulent viruses, GDVII and FA, which produce a rapidly fatal encephalitis in adult mice. All of the remaining isolates, referred to as TO strains because they resemble Theiler's original isolates (6), belong to the second group. These viruses are much less virulent than GDVII and FA but still cause central nervous system disease in the form of poliomyelitis (early onset) followed by a chronic, inflammatory demyelinating disease (late onset), which is due to viral persistence (4, 7). The difference in virulence between the two groups is substantial, on the order of magnitude of 2105 plaque-forming units per LD50 (8).Therefore, the existence of two distinct neurovirulence groups makes the TMEV particularly useful for studying the molecular pathogenesis of picornaviruses.Recently, we sequenced strains representing both neurovirulence groups, the highly virulent GDVII virus and the less virulent BeAn virus (2, 9). Computer-generated comparisons of GDVII and BeAn reveal 90.4% identity at the nucleotide level and 95.7% identity at the amino acid level (9). Because the 775 nucleotide and 99 amino acid differences are dispersed throughout the genome, sequence analysis alone is not sufficient to identify the genomic regions or gene products responsible for pathogenetic properties, such as virulence and attenuation.We have now constructed full-length cDNAs of the GDVII and BeAn virus RNAs and produced infectious transcripts in vitro. To identify the determinants...

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Section: Discussionmentioning

confidence: 99%

Genomic regions of neurovirulence and attenuation in Theiler murine encephalomyelitis virus.

Calenoff

Faaberg

Lipton

1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The 5'NCR (about 1 200 nt) is divided by a poly C tract located about 400 nt from the 5' end [41]. Little is known about the RNA region upstream of the poly C, except that a clover leaf structure is predicted at the 5' end [53]. A similar clover leaf structure found in poliovirus RNA is involved in the synthesis of positive strand RNA [7].…”

Section: Genomic Organisationmentioning

confidence: 99%

“…The poly C tract is present only in aphthoviruses and cardioviruses; its length varies among isolates [41,88] and it has been associated with viral virulence [114,253] although definitive proof is still lacking. Highly structured pseudoknot motives, present in different number among isolates [88], whose function remains unknown, are predicted downstream of the poly C [53]. The translation initiation of the FMDV RNA starts at two AUG codons separated by 84 nt [23], following ribosome recognition of the upstream internal ribosome entry site (IRES), which spans the 465 nt preceding the first functional AUG [26,132].…”

Section: Genomic Organisationmentioning

confidence: 99%

Foot-and-mouth disease virus: a long known virus, but a current threat

et al. 2001

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-Foot-and-mouth disease virus (FMDV) was the first animal virus identified. Since then, FMDV has become a model system in animal virology and a considerable amount of information on its structure, biology and vaccinology has been obtained. However, the disease that this virus produces (FMD) still constitutes one of the main animal health concerns. In this review, we have attempted to summarise the state of the knowledge in different basic and applied areas of FMDV research, with emphasis on those aspects relevant to the control of the disease. FMDV / structure / immunity / vaccine / variability / diagnosisRésumé -Le virus de la fièvre aphteuse : un virus connu de longue date, qui demeure une menace. Le virus de la fièvre aphteuse a été le premier virus animal identifié. Depuis lors, il est devenu un système modèle en virologie animale, et une quantité importante d'informations sur sa structure, sa biologie et sa vaccinologie a été obtenue. Cependant la maladie provoquée par ce virus constitue encore une inquiétude majeure en santé animale. Dans cette revue, nous avons tenté de résumer l'état des connaissances dans différents domaines de recherche, à la fois fondamentaux et appliqués, sur le virus de la fièvre aphteuse, en mettant l'accent sur les aspects relatifs au contrôle de la maladie. virus de la fièvre aphteuse / immunité / vaccin / variabilité / diagnostic

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“…The increased G + C content may reflect the fact that secondary structure plays an important role in the function of the 5' UTR, and stable structures can be derived by computer predictions. One folding model for the aphthoviruses predicts a highly ordered structure, much of the region consisting of a linear, double-stranded arrangement (Clarke et al, 1987). A second model, for which there are biochemical data derived from experiments with singleand double-strand-specific probes, is more complex and defines five main structural domains (Pilipenko et al, 1989a).…”

Section: G Stanwaymentioning

confidence: 99%