Journal of NeuroVirology

, Volume 25, Issue 4, pp 496–507 | Cite as

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

  • Natalia KučićEmail author
  • Valentino Rački
  • Kristina Jurdana
  • Marina Marcelić
  • Kristina Grabušić


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.


Microglia Murine cytomegalovirus BV-2 cells 


Funding information

This work was supported by the University of Rijeka Grant No.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

13365_2019_750_MOESM1_ESM.png (3.1 mb)
ESM 1 Pre-treatment of BV-2 microglia with IFN-γ induces less permissive cell phenotype regarding MCMV infection. Immunofluorescence of MCMV-infected BV-2 microglial cells cultivated in two different conditions (BV-2FCShigh / BV-2∅FCS) and pre-treated with 100 UI/ml of IFN-γ for 24 h prior infection. IFN-γ added to the cell cultures induced changes reflected with more ramified morphology and a significant increase of iNOS expression. IE1 viral protein expression was significantly decreased in both cultivated conditions upon infection. (PNG 3164 kb)


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© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  1. 1.Department of Physiology and Immunology, Faculty of MedicineUniversity of RijekaRijekaCroatia
  2. 2.Department of BiotechnologyUniversity of RijekaRijekaCroatia

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