New advances in animal and human virus vaccines.
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Amino Acid Sequence↗
Biomedical subjects
D J Rowlands
Publications and source records attributed to D J Rowlands.
Novel approaches to foot and mouth disease vaccination.
In view of the problems associated with the use of conventional foot and mouth disease (FMD) vaccines, such as antigenic variability of the FMD virus, the cost of vaccination programmes and problems associated with vaccine storage, alternative approaches to the design of FMD virus are discussed. Identification of the antigenic site of the FMD virus and isolation or synthesis of the peptides which make up the antigenic site are considered for vaccine use.
Animals↗
The sequence of foot-and-mouth disease virus RNA to the 5' side of the poly(C) tract.
The nucleotide sequence of foot-and-mouth disease virus (FMDV) RNA to the 5' side of the poly(C) tract (S fragment) has been determined for representatives of the A and O serotypes of the virus. The two S fragments differ in length by five nucleotides (nt), with 367 nt for O1 compared with 362 nt for A10, due to a number of insertions/deletions. However, the two sequences show 86% homology. There are no conserved open reading frames (ORFs). Secondary structure predictions reveal a high degree of potential base-pairing, such that the entire S fragment sequence can be folded into a hairpin structure.
Aphthovirus↗
Immunological priming with synthetic peptides of foot-and-mouth disease virus.
A sub-immunizing dose of a synthetic peptide corresponding to the amino acids 141 to 160 region of protein VP1 from foot-and-mouth disease virus (FMDV), serotype O1, coupled to keyhole limpet haemocyanin (141-160KLH) has been shown to prime the immune system of guinea-pigs for an FMDV serotype-specific neutralizing antibody response to a second sub-immunizing dose of the same peptide. Optimal priming required an interval of 42 days between the priming dose and the booster dose. No priming was observed in the absence of adjuvant. The secondary response was not restricted by the carrier since animals primed with 141-160KLH could be boosted with uncoupled 141-160 or 141-160 coupled to tetanus toxoid. It has also been shown that uncoupled peptide 141-160 will prime for a neutralizing antibody response when it is incorporated into a relatively non-immunogenic carrier such as small unilamellar liposomes. These results indicate that the 141-160 peptide of FMDV, as well as containing an important neutralizing antibody site, can initiate its own T-helper cell response.
Adjuvants, Immunologic↗
Two initiation sites for foot-and-mouth disease virus polyprotein in vivo.
Typically, the translation of eukaryotic mRNAs into protein is initiated at a single site. However, we have recently shown that not one but two primary products, P20a and P16, are translated from the 5' end of the coding region of the genome of foot-and-mouth disease virus (FMDV). In this paper we show by partial protease digestion of these proteins that they differ only at their N termini, thus confirming the presence of two initiation sites for translation of FMDV RNA. Sequence analysis of two subtypes of the virus (A10 and A12) confirms the presence of two initiator AUG codons in the expected position on the genome. By correlation with protein synthesis data from these subtypes it appears that the relative use of each initiation site is dependent on its surrounding nucleotide sequence. In addition, the ratio of the two proteins when synthesized in vitro differs markedly from that when they are synthesized in vivo, suggesting the presence of a control mechanism for synthesis of P20a in vivo which may be absent in vitro. We also show that the cleavage site between these two proteins and the structural protein precursor, P88, is located closer to the N terminus of the polyprotein than has previously been reported.
Aphthovirus↗
Magnetic resonance (MR) cine imaging of the human heart.
A novel approach has been developed for MR cine imaging of the human heart by a modified ECG-gated 2DFT method. A pulse sequence has been devised to minimise the effects of saturation which can be anticipated in sequences that require rapid pulsing. Five frames are produced at the same anatomical level at predetermined intervals during the cardiac cycle. The total time taken to achieve this data is 8 minutes. Additional frames can be interleaved by repeating the sequence with an ECG-gated delay. The anatomical sections, which can be in any orthogonal plane, are then displayed as a cine loop. Cine display in the coronal plane has been used to examine 10 volunteers and 12 patients. In addition to the morphological feature displayed in single slice ECG-gated imaging, areas of dyskinesia can be detected and subjective estimates have been made of left ventricular function.
Electrocardiography↗
The complete nucleotide sequence of the RNA coding for the primary translation product of foot and mouth disease virus.
The complete nucleotide sequence of the coding region of foot and mouth disease virus RNA (strain A1061) is presented. The sequence extends from the primary initiation site, approximately 1200 nucleotide from the 5' end of the genome, in an open translational reading frame of 6,999 nucleotides to a termination codon 93 nucleotides from the 3' terminal poly (A). Available amino acid sequence data correlates with that predicted from the nucleotide sequence. The amino acid sequence around cleavage sites in the polyprotein shows no consistency, although a number of the virus-coded protease cleavage sites are between glutamate and glycine residues.
Amino Acid Sequence↗
Synthetic peptides in foot and mouth disease vaccine research.
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Animals↗
Left and right bundle branch block, left anterior and left posterior hemiblock.
The data available on the prognosis of the intraventricular conduction disturbances--left and right bundle branch block (LBBB, RBBB) and left anterior and posterior hemiblock (LAH, LPH)--are uneven. However, there is no evidence to suggest that incomplete RBBB, established complete RBBB or established LAH carry other than a normal prognosis. Data on incomplete LBBB and on established LPH are insufficient to support conclusions. There are no adequate data on the risks of recently acquired LAH or LPH. Recently acquired isolated RBBB appears to carry little or no additional risk but the data are scant. It requires evaluation and may justify restriction to multi-crew operation. Established LBBB carries a small but definite increase in mortality risk, but subject to assessment it may be permissible in multi-crew operation. Recently acquired LBBB carries a substantial increase in mortality risk and should be disqualifying to fly.
Adult↗
Multiple proteases in foot-and-mouth disease virus replication.
Translation of foot-and-mouth disease virus RNA in a rabbit reticulocyte lysate for short time intervals resulted in the production of the peptides P20a , P16, and P88 (Lab, Lb, and P1) (R. R. Rueckert , Recommendations of the 3rd European Study Group on Molecular Biology of Picornavirus, Urbino , Italy, 1983). If further translation was prevented, the structural protein precursor P88 was not cleaved, even after prolonged incubation. This result indicates that the mechanism of the cleavage between P20a -P16 and P88 and of that between P88 and P52 (P2) differs from the mechanism of the secondary cleavages which produce the structural proteins. Furthermore, treatment of foot-and-mouth disease virus-infected cells with the protease inhibitor D-valyl phenylalanyl lysyl chloromethyl ketone prevented the in vivo cleavage between P20a -P16 and P88 but had no effect on any of the other cleavage events. These results suggest that the cleavage of the foot-and-mouth disease virus polyprotein utilizes two different host proteases.
Animals↗
Mimicking foot-and-mouth disease virus antigens with synthetic peptides.
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Animals↗
Synthetic peptides mimic subtype specificity of foot-and-mouth disease virus.
The major immunogen of foot-and-mouth disease virus (FMDV) is located between amino acids 141-160 of the capsid protein VP1. Synthetic peptides corresponding to the major immunogenic region give good neutralising antibody responses and protection in guinea pigs. To define more precisely the immunogenic site of the virus, we have examined serological differences between subtypes of the A serotype using synthetic peptides covering the 141-160 region. We show that these synthetic peptides carry determinants which mimic the subtype specificity of the virus. The correlation between these results and predictive structural models, based on the amino acid sequence, is discussed.
Amino Acid Sequence↗
Left atrial myxoma.
Intracardiac myxoma is a rare condition. In 75 per cent of cases the tumour arises in the left atrium and the number of possible modes of presentation is considerable. An incorrect clinical diagnosis is often made initially (Table 4). Correct diagnosis is of the greatest importance since operative removal is usually curative. If the diagnosis is delayed or is not made, or if surgery is delayed once the diagnosis has been made, the consequences for the patient can be catastrophic.
Cardiac Catheterization↗
Comparison of the amino acid sequence of the major immunogen from three serotypes of foot and mouth disease virus.
Cloned cDNA molecules from three serotypes of FMDV have been sequenced around the VP1-coding region. The predicted amino acid sequences for VP1 were compared with the published sequences and variable regions identified. The amino acid sequences were also analysed for hydrophilic regions. Two of the variable regions, numbered 129-160 and 193-204 overlapped hydrophilic regions, and were therefore identified as potentially immunogenic. These regions overlap regions shown by others to be immunogenic.
Amino Acid Sequence↗
Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence.
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Amino Acid Sequence↗
The nucleotide sequence of cDNA coding for the structural proteins of foot-and-mouth disease virus.
The complete nucleotide sequence of cDNA coding for the structural capsid polypeptides of foot-and-mouth disease virus (FMDV) (strain A(10)61) has been determined. Portions of the flanking sequence coding for the nonstructural proteins p20a and p52 are also provided. The three larger structural polypeptides VP1, VP2 and VP3 have unmodified Mrs of 23248, 24649 and 24213, respectively. The size of the smaller polypeptide, VP4, can only be estimated at 7360 because the 5'-limit of its coding region is not yet known with certainty. The sequence data for VP1 (the major immunising antigen) and the amino-terminal quarter of p52 are compared with the data of Kurz et al. (Nucl. Acids Res. 9 (1981) 1919-1931) for a different serotype (O1K). This shows that variation is much greater in the region coding for VP1 than in that coding for p52. This is reflected in the level of amino acid sequence variation predicted for the two proteins. Analysis of relative codon usage reveals a strong bias in favour of C and G over U and A in the third base position. The dinucleotide frequencies show a bias against A-U and U-A, and for A-C and C-A.
Aphthovirus↗
Molecular cloning of foot and mouth disease virus genome and nucleotide sequences in the structural protein genes.
Foot and mouth disease virus (FMDV), of the family Picornaviridae, consists of a single-stranded RNA (approximately 8,000 nucleotides), the translation of which is initiated on the 3' side of a 150-nucleotide poly(C) tract and yields a single polyprotein which is processed by host cell proteases into four primary products (Fig. 1). One or more virus-specified proteases further cleave these into the final products, the capsid proteins (VP1-4) being derived from the precursor p88 (for review see ref. 5). There are seven serotypes of the virus and as it has been shown that the immunizing activity of FMDV particles is associated primarily with VP1 (refs 6, 7), it seems likely that antigenic variation in FMDV is a result of changes in the structure of this protein. To further our understanding of this variation and as a first step in the possible development of FMDV vaccines from genetically manipulated microorganisms, we report here the construction and analysis of recombinant plasmids containing cDNA copies of the RNA. Comparison of the deduced amino acid sequence with the known polypeptide sequences shows that the NH2-termini of VP2 and VP3 are conserved between the A and O serotypes whereas that of VP1 (the immunizing antigen) varies by as much as 42% between serotypes.
Amino Acid Sequence↗