Immunometabolic phenotype of BV-2 microglia cells upon murine cytomegalovirus infection

J Neurovirol. 2019 Aug;25(4):496-507. doi: 10.1007/s13365-019-00750-1. Epub 2019 Apr 25.


Microglia are resident brain macrophages with key roles in development and brain homeostasis. Cytomegalovirus (CMV) readily infects microglia cells, even as a possible primary target of infection in development. Effects of CMV infection on a cellular level in microglia are still unclear; therefore, the aim of this research was to assess the immunometabolic changes of BV-2 microglia cells following the murine cytomegalovirus (MCMV) infection. In light of that aim, we established an in vitro model of ramified BV-2 microglia (BV-2∅FCS, inducible nitric oxide synthase (iNOSlow), arginase-1 (Arg-1high), mannose receptor CD206high, and hypoxia-inducible factor 1α (HIF-1αlow)) to better replicate the in vivo conditions by removing FCS from the cultivation media, while the cells cultivated in 10% FCS DMEM displayed an ameboid morphology (BV-2FCS high, iNOShigh, Arg-1low, CD206low, and HIF-1αhigh). Experiments were performed using both ramified and ameboid microglia, and both of them were permissive to productive viral infection. Our results indicate that MCMV significantly alters the immunometabolic phenotypic properties of BV-2 microglia cells through the manipulation of iNOS and Arg-1 expression patterns, along with an induction of a glycolytic shift in the infected cell cultures.

Keywords: BV-2 cells; Microglia; Murine cytomegalovirus.

MeSH terms

  • Animals
  • Arginase / genetics
  • Arginase / immunology*
  • Cell Line
  • Culture Media, Serum-Free / pharmacology
  • Embryo, Mammalian
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Gene Expression Regulation
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / deficiency
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Mannose Receptor
  • Mannose-Binding Lectins / deficiency
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Microglia / immunology
  • Microglia / virology*
  • Models, Biological
  • Muromegalovirus / genetics*
  • Muromegalovirus / growth & development
  • Muromegalovirus / metabolism
  • Nitric Oxide Synthase Type II / deficiency
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / immunology*
  • Primary Cell Culture
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Signal Transduction


  • Culture Media, Serum-Free
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Arg1 protein, mouse
  • Arginase