Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence

Ryan, Martin; King, Andrew M. Q.; Thomas, Gilles

doi:10.1099/0022-1317-72-11-2727

Cited by 424 publications

(360 citation statements)

References 17 publications

(7 reference statements)

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“…In FMDV, the primary cleavage of the polyprotein occurs in cis and requires the 16 amino-acid long 2A sequence that mediates cleavage at its own Cterminus. 32,34 The mechanism by which the 2A sequence promotes this cleavage is not fully understood. It has been proposed that 2A represents either (a) a recognition site for a fairly ubiquitous protease associated with eukaryotic ribosomes; (b) an unusually short novel element of protein cleavage; or (c) a sequence that results in a failure to synthesize a peptide bond, yet allows the continuation of translation.…”

Section: Discussionmentioning

confidence: 99%

“…The 2A region in foot and mouth disease virus (FMDV) spans only 16 amino acids. 33,34 When engineered into heterologous fusion proteins, the FMDV 2A sequence has been shown to mediate cleavage both in vitro using eukaryotic translation systems, [33][34][35] as well as in plants 36,37 and cultured mammalian cells. 38,39 Recently, the FMDV 2A sequence has been incorporated into retroviral vectors, alone or combined with different IRES sequences to construct bicistronic, tricistronic and tetracistronic retroviral vectors.…”

Section: Introductionmentioning

confidence: 99%

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Recombinant AAV vectors containing the foot and mouth disease virus 2A sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons

et al. 2001

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Recombinant adeno-associated viruses (rAAVs) are promising vectors for gene therapy since they efficiently and stably transduce a variety of tissues of immunocompetent animals. The major disadvantage of rAAVs is their limited capacity to package foreign DNA (р5 kb). Often, co-expression of two or more genes from a single viral vector is desirable to achieve maximal therapeutic efficacy or to track transduced cells in vivo by suitable reporter genes. The internal ribosome entry site (IRES) sequence of encephalomyocarditis virus has been widely used to construct bicistronic viral vectors. However, the IRES is rather long and IRES-mediated translation can be relatively inefficient when compared with capdependent translation. As an alternative to the IRES for in vivo gene expression, we studied the 16 amino-acid long 2A peptide of foot and mouth disease virus (FMDV). The 2A peptide mediates the primary cis-'cleavage' of the FMDV polyprotein in a cascade of processing events that ultimately

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recombinant AAV vectors containing the foot and mouth disease virus 2A sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons

et al. 2001

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“…P2 region of the poly protein is processed into three mature polypeptides, 2A, 2B, and 2C [53]. 2A peptide remains associated with the P1 structural protein precursor following primary cleavage and appears to be an auto proteinase [57]. The picornaviral 2B and 2C proteins have been implicated in virus-induced cytopathic effects.…”

Section: Fmdv Genomementioning

confidence: 99%

Foot-and-mouth Disease: Global Status and Future Road Map for Control and Prevention in India

et al. 2012

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Foot-and-mouth disease (FMD) is a transboundary, economically devastating and highly contagious viral disease of livestock, most importantly cattle, buffalo and pig. The disease also affects goats, sheep, wild ruminant species and elephants. The causative FMD virus is antigenically diverse having seven distinct serotypes and many variants within them. Being a single stranded RNA virus, it confirms the quasispecies nature with emergences and reemergences of different genetic lineages with altered antigenicity within the serotypes, making vaccination based control programme a high cost effective, time consuming and difficult to achieve. As per the OIE and FAO, the disease is a major threat to food security of the world, and particularly the countries having the disease are more prone to food insecurity. Further, FMD free status is an indicator of development, and all developed countries are free from it. The disease is endemic in India and three serotypes of the virus viz; O, A and Asia1 are circulating. Annual direct loss due to FMD in India has been estimated at Rs. 20,000 crores. Many countries in the world are now free from FMD with or without vaccination and presence of the disease in other neighboring countries is a major threat to them. Countries having FMD face trade barrier posed by FMD free countries, causing heavy economic loss to the livestock industry. Progressive control pathway has been developed by FAO for global eradication of FMD. Vaccination based FMD control programme is in operation in India which involves biannual vaccinations of all cattle and buffaloes in selected areas, regular active surveillance and antibody monitoring in vaccinated population with the objective of creating FMD free zones. At present, the disease occurrence, severity of the clinical disease and number of outbreaks have progressively and substantially declined in the control zones as a result of last 10 rounds of vaccination with an oil adjuvanted trivalent inactivated vaccine. In this review, FMD scenario in India and in the world is briefed. Besides, the measures taken for the control and eradication of this devastating disease is presented. Besides, the initial success achieved through the FMD control programme in India, a road map for the control and eradication of FMD at national level is discussed.

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“…The following 2A peptides were utilized in the lentiviral vectors, insect virus T2A encodes EGRGSLLTCGD VEENPGP, F2A encodes APVKQTLNFDLLKLAGDVES NPGP and P2A encodes ATNFSLLKQAGDVEE NPGP. 25,29,54 Supplementary Table 1 contains all primer sequences. The primer flanking 5 0 of gp100 (154) TCR-a chain (154A5 0 ) and primer flanking 3 0 of gp100 (154) bchain (154B3 0 ) containing AscI and SalI restrictive enzyme sites were designed for all the following constructs, including fuT2A, fuSGSGT2A, F2A, fuSGSG F2A and fuSGSGP2A and so on.…”

Section: Vector Constructionmentioning

confidence: 99%

Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition

et al. 2008

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In human gene therapy applications, lentiviral vectors may have advantages over g-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike g-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust antimelanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy.

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Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence

Cited by 424 publications

References 17 publications

Recombinant AAV vectors containing the foot and mouth disease virus 2A sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons

Recombinant AAV vectors containing the foot and mouth disease virus 2A sequence confer efficient bicistronic gene expression in cultured cells and rat substantia nigra neurons

Foot-and-mouth Disease: Global Status and Future Road Map for Control and Prevention in India

Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition

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