Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

Virology. 2017 Oct:510:205-215. doi: 10.1016/j.virol.2017.07.023. Epub 2017 Jul 24.

Abstract

T98G cells have been shown to support long-term human cytomegalovirus (HCMV) genome maintenance without infectious virus release. However, it remains unclear whether these viral genomes could be reactivated. To address this question, a recombinant HCMV (rHCMV) containing a GFP gene was used to infect T98G cells, and the infected cells absent of infectious virus production were designated T98G-LrV. Upon dibutyryl cAMP plus IBMX (cAMP/IBMX) treatment, a serial of phenomena were observed, including GFP signal increase, viral genome replication, lytic genes expression and infectious viruses release, indicating the reactivation of HCMV in T98G-LrV cells from a latent status. Mechanistically, HCMV reactivation in the T98G-LrV cells induced by cAMP/IBMX was associated with the PKA-CREB signaling pathway. These results demonstrate that HCMV was latent in T98G-LrV cells and could be reactivated. The T98G-LrV cells represent an effective model for investigating the mechanisms of HCMV reactivation from latency in the context of neural cells.

Keywords: Human cytomegalovirus; Latent cell model of brain origin; Latent infection; Reactivation; T98G cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / metabolism
  • Bucladesine / metabolism
  • Cell Line, Tumor
  • Cytomegalovirus / physiology*
  • Genes, Reporter
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Staining and Labeling / methods
  • Virus Activation*
  • Virus Latency*

Substances

  • Green Fluorescent Proteins
  • Bucladesine
  • 1-Methyl-3-isobutylxanthine