title: The effect of cellular differentiation on HSV-1 infection of oligodendrocytic cells.
abstract: Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects many types of cells. Previous studies have demonstrated that oligodendrocytic cells are highly susceptible to HSV-1 infection. Here we analysed HSV-1 infection of a human oligodendrocytic cell line, HOG, and oligodendrocyte precursor cells (OPCs) cultured under growth or differentiation conditions. In addition to cell susceptibility, the role of the major cell receptors for viral entry was assessed. Our results revealed that OPCs and HOG cells cultured under differentiation conditions became more susceptible to HSV-1. On the other hand, viral infection induced morphological changes corresponding to differentiated cells, suggesting that HSV-1 might be inducing cell differentiation. We also observed colocalization of HVEM and nectin-1 with viral particles, suggesting that these two major HSV-1 receptors are functional in HOG cells. Finally, electron microscopy assays indicated that HSV-1 may be also entering OLs by macropinocytosis depending on their differentiation stage. In addition, vesicles containing intracellular enveloped virions observed in differentiated cells point to an endocytic mechanism of virus entry. All these data are indicative of diverse entry pathways dependent on the maturation stage of OLs.
authors.affiliation: Universidad Autónoma de Madrid, Departamento de Biología Molecular, Edificio de Biología, Darwin 2, Cantoblanco, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bello-Morales
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
authors.forename: Antonio Jesús
authors.initials: AJ
authors.lastname: Crespillo
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García
authors.affiliation: Universidad Autónoma de Madrid, Departamento de Biología Molecular, Edificio de Biología, Darwin 2, Cantoblanco, Madrid, Spain.
authors.forename: Luis Ángel
authors.initials: LÁ
authors.lastname: Dorado
authors.affiliation: Universidad Autónoma de Madrid, Facultad de Medicina, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín
authors.affiliation: Universidad Autónoma de Madrid, Facultad de Medicina, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Tabarés
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia Pennsylvania, United States of America.
authors.forename: Claude
authors.initials: C
authors.lastname: Krummenacher
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Castro
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Guerrero
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D004705:Endocytosis; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D000075983:Nectins; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics* / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human