Disease relevance of PestiV1gp1

• Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication [1].
• A region of the predicted polyprotein sequence was found to share similarity with a nonstructural protein encoded by dengue virus, a member of the flavivirus family [2].
• The polyprotein of classical swine fever virus starts with the nonstructural protein p23, which is followed by the nucleocapsid protein p14 [3].
• Polyprotein processing control is a crucial step in the life cycle of positive-strand RNA viruses [4].
• This finding indicates that the 3' limit of the GBV-B IRES is at the initiator AUG and that it does not require downstream polyprotein-coding sequence as suggested for the HCV IRES [5].

High impact information on PestiV1gp1

• Preceding the polyprotein start codon, multiple cryptic AUG codons and several small open reading frames are characteristic for all the five pestiviruses [6].
• Pestiviruses belong to the family Flaviviridae, and their genome is a single-stranded RNA of positive polarity encoding one large polyprotein which is further processed into mature proteins [7].
• Genetic analysis revealed that indeed a single nucleotide change encoding proline at NS5B position 726 in the pseudorevertant polyprotein mediated recovery of virion assembly function without improving genomic RNA accumulation levels [8].
• Gene expression of these viruses occurs via translation of a polyprotein, which is further processed by cellular and viral proteases [9].
• We show here that translation of its polyprotein is initiated by internal entry of ribosomes on GBV-B RNA [5].

Chemical compound and disease context of PestiV1gp1

• This N-terminal protease (Npro) cleaves itself off of the nascent polyprotein autocatalytically and thereby generates the N terminus of the adjacent viral capsid protein C. In previous reports, sequence similarities between Npro and the catalytic residues of papain-like cysteine proteases were put forward [10].
• Classical swine fever virus (CSFV) E2 glycoprotein contains a discrete epitope (TAVSPTTLR, residues 829-837 of CSFV polyprotein) recognized by monoclonal antibody (mAb) WH303, used to differentiate CSFV from related ruminant pestiviruses, Bovine Viral Diarrhea Virus (BVDV) and Border Disease Virus (BDV), that infect swine without causing disease [11].

Biological context of PestiV1gp1

• The pestivirus genome encodes a single polyprotein which is subject to co- and posttranslational processing by cellular and viral proteases [12].
• While polyprotein proteolysis was found to be almost unaffected in these latter replicons, in vitro studies with the purified mutant NS3 proteins revealed a significantly impaired helicase activity for the motif II substitutions [13].
• The amino acid sequence of the polyprotein deduced from the nucleotide sequence of the Japanese hepatitis C virus genome (N. Kato et al. (1990) Proc. Natl. Acad. Sci. USA 87, 9524-9528) indicated that this virus is a member of a new class of positive-stranded RNA viruses [14].
• Several properties of this polyprotein, like hydrophobicity, position of putative protease cleavage sites, distribution of N-linked glycosylation sites, distribution of cysteines and distribution of acidic and basic residues are described and discussed [15].
• The candidate peptide epitopes were identified by using the computer programs available as a part of the Genetics Computer Group package and applying the information on allele-specific peptide motifs and intracellular enzymatic cleavage patterns to the bovine viral diarrhea virus polyprotein [16].

Anatomical context of PestiV1gp1

• The single best-defined, SLA-I restricted porcine CD8(+) T-cell epitope currently known is a 9-residue peptide from the polyprotein of CSFV (J. Gen. Virol. 76 (1995) 3039) [17].

Associations of PestiV1gp1 with chemical compounds

• The NS3 serine protease is not involved in this cleavage, which, according to protein sequencing, occurs between amino acids 1589 and 1590 of the BVDV Oregon polyprotein [18].
• Three hypervariable regions were identified in the polyprotein-encoding region, with one of them comprising a sequence motif encoding a unique five amino acid peptide HYKKK in glycoprotein E2 gene [19].

Analytical, diagnostic and therapeutic context of PestiV1gp1

• Sequence analysis of the E(rns) genes of these virus clones before and after amplification in SK6 cells showed that passage in SK6 cells resulted in a change of an Ser residue to an Arg residue in the C terminus of E(rns) (amino acid 476 in the polyprotein of CSFV) [20].
• By co- and sequential immunoprecipitation we showed that an E(rns)-E2 heterodimer is assembled very early after translation of the viral polyprotein and before its processing is completed [21].

References