Disease relevance of TCRVsSgp1

• The envelope glycoprotein of the arenaviruses (GP-C) is unusual in that the mature complex retains the cleaved, 58-amino-acid signal peptide [1].
• These are completely conserved among the predicted polyprotein sequences of all the CCHF virus strains and closely resemble the tetrapeptides that represent the major cleavage recognition sites present in the glycoprotein precursors of arenaviruses, such as Lassa fever virus (RRLL) and Pichinde virus (RKLL) [2].
• Having established that the heterologous glycoprotein protects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV-GJun) [3].
• Effect of inhibitors of the intracellular exocytic pathway on glycoprotein processing and maturation of Junin virus [4].
• Drug resistant variants were isolated, suggesting that these compounds act through inhibition of a viral protein, the viral glycoprotein (GP2), and not through cellular toxicity mechanisms [5].

High impact information on TCRVsSgp1

• Alanine substitution for the modified glycine residue in the GP-C signal peptide does not affect formation of the tripartite envelope glycoprotein complex but markedly reduces its membrane fusion activity [6].
• In contrast to the classical view that signal peptides act primarily in targeting nascent polypeptides to the endoplasmic reticulum, we suggest that the signal peptide of the arenavirus GP-C may serve additional functions in envelope glycoprotein structure and trafficking [6].
• The TV genome encodes four proteins, the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a small RING finger protein (Z) [7].
• A low pH-pulse, induces fusion of Vero cells infected with JV to form syncytia, whose production can be inhibited by neutralizing antibodies against the JV major glycoprotein [8].
• N-linked oligosaccharides, mannose and galactose were found as terminal residues in the JV-G1 glycoprotein [9].

Chemical compound and disease context of TCRVsSgp1

• The influence of glycoprotein processing, cleavage and transport on Junin virus (JV) infectivity was investigated using monensin combined with lectin binding assays [10].
• The effect of glycoprotein processing and transport on Junin virus (JV) maturation was studied by using brefeldin A (BFA) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), two inhibitors affecting different steps of the intracellular exocytic pathway, combined with low temperature incubation [4].
• The biological properties mediated by the main envelope glycoprotein (GP1) of a mouse-attenuated mutant of Junin virus, named Cl67, were investigated in comparison with its parental strain XJCl3 [11].

Anatomical context of TCRVsSgp1

• The cytoskeleton retained nearly 70% of the external JV envelope glycoprotein GP38 and about 40% of the JV nucleoprotein NP, according to TX-100 and OG insolubility results [12].
• Neutralizing antibodies against the main viral glycoprotein (GP38) inhibited syncytium production and GP38 conformational changes in response to acid treatment were detected by an immunoprecipitation assay [13].
• Thus, GP38 production together with glycoprotein transport to the cell membrane seemed to be required for the release of infectious virus from JV-infected cells [10].
• Thus, results obtained with BFA allow to conclude that the proteolytic processing of GPC probably occurs at the trans-Golgi network and this cleavage together with the glycoprotein presence at the cell surface is required for maturation of infectious JV particles [4].

References