title: Subcellular Trafficking and Functional Relationship of the HSV-1 Glycoproteins N and M.
abstract: The herpes simplex virus type 1 (HSV-1) glycoprotein N (gN/UL49.5) is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM and gN are covalently linked by a single disulphide bond formed between cysteine 46 of gN and cysteine 59 of gM. Exit of gN from the endoplasmic reticulum requires the N-terminal core of gM composed of eight transmembrane domains but is independent of the C-terminal extension of gM. Co-transport of gN and gM to the trans Golgi network also occurs upon replacement of conserved cysteines in gM and gN, suggesting that their physical interaction is mediated by covalent and non-covalent forces. Deletion of gN/UL49.5 using bacterial artificial chromosome (BAC) mutagenesis generated mutant viruses with wild-type growth behaviour, while full deletion of gM/UL10 resulted in an attenuated phenotype. Deletion of gN/UL49.5 in conjunction with various gM/UL10 mutants reduced average plaque sizes to the same extent as either single gM/UL10 mutant, indicating that gN is nonessential for the function performed by gM. We propose that gN functions in gM-dependent as well as gM-independent processes during which it is complemented by other viral factors.
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-University München, Munich 80336, Germany. h.striebinger@yahoo.de.
authors.forename: Hannah
authors.initials: H
authors.lastname: Striebinger
authors.affiliation: Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, Stuttgart 70569, Germany. Christina.Funk@igb.fraunhofer.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Funk
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-University München, Munich 80336, Germany. verenarasch@gmail.com.
authors.forename: Verena
authors.initials: V
authors.lastname: Raschbichler
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-University München, Munich 80336, Germany. Susanne.Bailer@igvp.uni-stuttgart.de.|Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, Stuttgart 70569, Germany. Susanne.Bailer@igvp.uni-stuttgart.de.|Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart 70569, Germany. Susanne.Bailer@igvp.uni-stuttgart.de.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Bailer
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D053586:Virus Internalization
chemical_list: D008562:Membrane Glycoproteins; C081689:UL10 protein, Human herpesvirus 1; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C076024:UL49A protein, Human herpesvirus 2
keywords: HSV-1; UL10; UL49.5; glycoprotein M; glycoprotein N; herpesvirus