Journal Article

Identification of the Cleavage Domain within Glycoprotein G of Herpes Simplex Virus Type 2

Kropp, Kai A., Pich, Andreas, Viejo-Borbolla, Abel, Srivaratharajan, Sangar, Alcami, Antonio, Yu, Pengfei, Polten, Felix, Ritter, Birgit, Krooss, Simon

2020

Overview

Glycoprotein G (gG) from herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) functions as a viral chemokine binding protein (vCKBP). Soluble recombinant forms of gG of HSV-1 and HSV-2 (SgG1 and SgG2, respectively) enhance chemokine-mediated leukocyte migration, in contrast to most known vCKBPs, including those from animal alpha-herpesviruses. Furthermore, both proteins bind to nerve growth factor (NGF), but only SgG2 enhances NGF-dependent neurite outgrowth. The basis and implications of this functional difference between the two proteins are still unknown. While gG1 and gG2 are positional homologues in the genome, they share very limited sequence homology. In fact, US4, the open reading frame encoding gG is the most divergent genetic locus between these viruses. Full-length gG1 and gG2 are type I transmembrane proteins located on the plasma membrane of infected cells and at the viral envelope. However, gG2 is larger than gG1 and is cleaved during protein maturation, secreting the N-terminal domain to the supernatant of infected cells, whereas gG1 is not. The enzyme involved in gG2 cleavage and the functional relevance of gG2 cleavage and secretion are unknown. We aim to identify the gG2 sequence required for cleavage to determine its functional role in future experiments. Our results prove the existence of at least two cleavage motifs in gG2 within the amino acid region 314-343. Transfer of this sequence to a fusion protein results in cleavage. Finally, we show that propeptide convertases like furin are responsible for gG2 cleavage.

• Publisher: MDPI AG,MDPI
• Subject: Amino Acid Motifs / Amino Acid Sequence / Amino acids / Animals / Axonogenesis / Cell Line / cell movement / Chemokines / Chromatography, Liquid / Cloning / Deoxyribonucleic acid / DNA / enzymes / Furin / Fusion protein / Gene Expression / Genes, Reporter / genome / Genomes / glycoprotein / Glycoprotein G / Glycoproteins / Herpes simplex / Herpes Simplex - virology / herpes simplex virus / Herpes viruses / Herpesvirus 2, Human - physiology / HIV / Homology / Human alphaherpesvirus 1 / Human alphaherpesvirus 2 / Human immunodeficiency virus / Humans / Leukocyte migration / loci / Mass Spectrometry / Membrane proteins / Mutation / Nerve growth factor / neurites / Nucleotide sequence / Penicillin / plasma membrane / Plasmids / protein cleavage / Protein Interaction Domains and Motifs / Proteins / Proteolysis / secretion / sequence homology / Viral Envelope Proteins - metabolism