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PLoS One. 2014 Feb 13;9(2):e89141. doi: 10.1371/journal.pone.0089141. eCollection 2014.

The effect of cellular differentiation on HSV-1 infection of oligodendrocytic cells.

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Universidad Autónoma de Madrid, Departamento de Biología Molecular, Edificio de Biología, Darwin 2, Cantoblanco, Madrid, Spain.
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
Universidad Autónoma de Madrid, Facultad de Medicina, Madrid, Spain.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia Pennsylvania, United States of America.
Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain.


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.

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