Disease relevance of MVEVgp1

• Safety and immunogenicity of NYVAC-based recombinants expressing the rabies virus glycoprotein, a polyprotein from Japanese encephalitis virus, and seven antigens from Plasmodium falciparum have been demonstrated to be safe and immunogenic in early human vaccine studies [1].
• Signal peptidase cleavage at the C-prM junction in the flavivirus structural polyprotein is inefficient in the absence of the cytoplasmic viral protease, which catalyzes cleavage at the COOH terminus of the C protein [2].
• In this study, we used cDNA of Murray Valley encephalitis virus (MVE) to examine features of the structural polyprotein which allow this regulation of a luminal cleavage by a cytoplasmic protease [2].
• The West Nile Virus (WNV) non-structural proteins 2B and 3 (NS2B-NS3) constitute the proteolytic complex that mediates the cleavage and processing of the viral polyprotein [3].
• The cell-associated WN virus particles are constructed from the proteins C, pre-M, and E which contain the amino residues 1-105, 124-290, and 291-787 of the polyprotein, respectively [4].

High impact information on MVEVgp1

• WNV has a positive strand RNA genome of about 11 kb that encodes a single polyprotein [5].
• We show that control of signalase cleavage of the multimembrane-spanning flavivirus polyprotein by the catalytic function of the viral protease is critical for efficient virus morphogenesis [6].
• We also examined the effect of proteolytic processing in the MVE nonstructural polyprotein segment mediated by the viral proteinase NS3 on antigen processing and presentation of the MVE H-2Kk-restricted T cell determinant [7].
• The proteolytic processing of a non-structural polyprotein segment from the cytoplasmic domain of NS2A to the C terminus of NS5 of Murray Valley encephalitis (MVE) virus was examined, when expressed from cDNA via a vaccinia virus recombinant, in transiently transfected COS cells, or synthesized by cell-free translation [8].
• Similarly, substitution of residue histidine 51 of the NS3 polyprotein segment, which is predicted to be part of the protease catalytic centre, with an alanine residue, blocks the processing of the polyprotein in vitro [9].

Chemical compound and disease context of MVEVgp1

• A common genomic organization and molecular mechanisms of replication in hosts are shared by flaviviruses with a viral serine protease playing a pivotal role in processing the viral polyprotein into component polypeptides, an obligatory step in viral replication [10].

Biological context of MVEVgp1

• Partial N-terminal amino acid analyses of KUN virus-specified proteins identified the polyprotein cleavage sites and the definitive gene order [11].
• Terminal sequencing revealed that the N- and C-termini of NS1(o) were located at amino acid positions 714 and 1145 in the polyprotein respectively, consistent with the predicted sites based upon sequence homology with other flaviviruses [12].
• The flavivirus non-structural glycoprotein NS1 is often detected in Western blots as a heterogeneous cluster of bands due to glycosylation variations, precursor-product relationships and/or alternative cleavage sites in the viral polyprotein [12].

Anatomical context of MVEVgp1

• The amino-terminal part of the polyprotein containing the amino acid residues 1 to 123 is released as a molecule which migrates slightly slower than the mature viral core protein and which presumably is associated to the RER membranes via its carboxy-terminal sequence [4].

Associations of MVEVgp1 with chemical compounds

• Virus neutralizing antibody was demonstrated in 18/20 E glycoprotein recipients and 15/20 polyprotein recipients [13].

Analytical, diagnostic and therapeutic context of MVEVgp1

• Termination codons were introduced by site-directed mutagenesis at the junctions of the NS3-4A, NS4A-4B and NS4B-5 genes to generate C-terminal truncations of the MVE virus polyprotein segment [8].

References