The Two Species of the Foot-and-Mouth Disease Virus Leader Protein, Expressed individually, Exhibit the Same Activities

Medina, Miguel; Domingo, Esteban; Brangwyn, Julia K.; Belsham, Graham J.

doi:10.1006/viro.1993.1267

Cited by 139 publications

(129 citation statements)

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“…1). As already mentioned, the L protease cleaves the translation initiation factor eIF4G (Lopez de Quinto & Martinez-Salas, 2000;Medina et al, 1993), and in the late steps of infection the 3C protease also processes eIF4G (Strong & Belsham, 2004). Enterovirus and rhinovirus genomes also encode two proteases, 2A and 3C (Fig.…”

Section: Ires Activity Is Resistant To Specific Host Protein Cleavagementioning

confidence: 83%

New insights into internal ribosome entry site elements relevant for viral gene expression

Martínez‐Salas

Pacheco

Serrano

et al. 2008

Journal of General Virology

119

106

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A distinctive feature of positive-strand RNA viruses is the presence of high-order structural elements at the untranslated regions (UTR) of the genome that are essential for viral RNA replication. The RNA of all members of the family Picornaviridae initiate translation internally, via an internal ribosome entry site (IRES) element present in the 59 UTR. IRES elements consist of cis-acting RNA structures that usually require specific RNA-binding proteins for translational machinery recruitment. This specialized mechanism of translation initiation is shared with other viral RNAs, e.g. from hepatitis C virus and pestivirus, and represents an alternative to the cap-dependent mechanism. In cells infected with many picornaviruses, proteolysis or changes in phosphorylation of key host factors induces shut off of cellular protein synthesis. This event occurs simultaneously with the synthesis of viral gene products since IRES activity is resistant to the modifications of the host factors. Viral gene expression and RNA replication in positive-strand viruses is further stimulated by viral RNA circularization, involving direct RNA-RNA contacts between the 59 and 39 ends as well as RNA-binding protein bridges. In this review, we discuss novel insights into the mechanisms that control picornavirus gene expression and compare them to those operating in other positive-strand RNA viruses.

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Section: Ires Activity Is Resistant To Specific Host Protein Cleavagementioning

confidence: 83%

New insights into internal ribosome entry site elements relevant for viral gene expression

Martínez‐Salas

Pacheco

Serrano

et al. 2008

Journal of General Virology

119

106

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“…It has been shown to be important in virulence and in the inhibition of interferon production (52,107,108). The L protein of FMDV is a cysteine protease responsible for early cleavage of the translation initiation factor eIF4G during FMDV infection, resulting in the rapid inhibition of host cell protein synthesis (109,110). The L* protein of TMEV subgroup DA (or TO) strains, unlike the N pro and L proteins, is synthesized from an ORF overlapping that of the polyprotein.…”

Section: Possible Functional Relationships With Other Viral Proteinsmentioning

confidence: 99%

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Vassilaki

Mavromara

2009

IUBMB Life

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Hepatitis C virus (HCV) is an enveloped positive‐strand RNA virus of the Flaviviridae family. It has a genome of about 9,600 nucleotides encoding a large polyprotein (about 3,000 amino acids) that is processed by cellular and viral proteases into at least 10 structural and nonstructural viral proteins. A novel HCV protein has also been identified by our laboratory and others. This protein—known as ARFP (alternative reading frame protein), F (for frameshift) or core+1 (to indicate the position) protein ‐ is synthesized by an open reading frame overlapping the core gene at nucleotide +1 (core+1 ORF). However, almost 10 years after its discovery, we still know little of the biological role of the ARFP/F/core+1 protein. Abolishing core+1 protein production has no affect on HCV replication in cell culture or uPA‐SCID mice, suggesting that core+1 protein is probably not important for the HCV reproductive cycle. However, the detection of specific anti‐core+1 antibodies and T‐cell responses in HCV‐infected patients, as reported by many independent laboratories, provides strong evidence that this protein is produced in vivo. Furthermore, analyses of the HCV sequences isolated from patients with hepatocellular carcinoma and in vitro studies have provided strong preliminary evidence to suggest that core+1 protein plays a role in advanced liver disease and liver cancer. The available in vitro data also suggest that certain core function proteins may depend on production of the core+1 protein. We describe here the discovery of the various forms of the core+1 protein and what is currently known about the mechanisms of their production and their biochemical and functional properties. We also provide a detailed summary of the results of patient‐based research. © 2009 IUBMB IUBMB Life, 61(7): 739–752, 2009

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“…As protein synthesis can initiate at one of two AUG codons lying 84 nucleotides apart, L pro exists in one of two forms, termed Lab pro and Lb pro . Both forms possess the same enzymic activities [7].…”

Section: Introductionmentioning

confidence: 99%

Modulation of the electrostatic charge at the active site of foot-and-mouth-disease-virus leader proteinase, an unusual papain-like enzyme

Schlick

Kronovetr

Hampoelz

et al. 2002

Biochemical Journal

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The leader proteinase (Lpro) of foot-and-mouth-disease virus is an unusual papain-like cysteine proteinase. Synthesized without an N-terminal pro precursor region, it frees itself from the growing polypeptide chain by cleavage at its own C-terminus. It also possesses a unique electrostatic environment around the active site, essentially due to Asp163, which orients the catalytic histidine residue, and Asp164; the equivalent residues in papain are Asn175 and Ser176. The importance of these residues for Lpro activity was examined by site-directed mutagenesis. Replacement of Asp163 with asparagine reduced activity by five-fold towards a hexapeptide substrate and slightly delayed self-processing when expressed in rabbit reticulocyte lysates. However, no effect on the cleavage of the only known cellular substrate of Lpro, eukaryotic initiation factor 4GI (eIF4GI), was observed. In contrast, replacement of Asp164 by either alanine, asparagine or lysine abrogated activity towards the hexapeptide. Furthermore, in all cases, the onset of both self-processing and eIF4GI cleavage were significantly delayed; the reaction rates were also diminished compared with those of the wild-type enzyme. The alanine-substituted enzyme was least affected, followed by those substituted with asparagine and lysine. The double mutant protein in which both aspartate residues were replaced by asparagine was most severely affected; it failed to complete either self-processing or eIF4GI cleavage within 3 h, compared with the 8min required by the wild-type enzyme. Hence, we propose that the electrostatic charge of Asp164, and to a lesser extent that of Asp163, is extremely important for Lpro to attain full activity upon synthesis.

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The Two Species of the Foot-and-Mouth Disease Virus Leader Protein, Expressed individually, Exhibit the Same Activities

Cited by 139 publications

References 0 publications

New insights into internal ribosome entry site elements relevant for viral gene expression

New insights into internal ribosome entry site elements relevant for viral gene expression

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Modulation of the electrostatic charge at the active site of foot-and-mouth-disease-virus leader proteinase, an unusual papain-like enzyme

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