4.4 Article

Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

Journal

VIROLOGY
Volume 510, Issue -, Pages 205-215

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2017.07.023

Keywords

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

Categories

Funding

  1. National Natural Science Foundation of China [81601770]
  2. Applied Basic Research Program of Wuhan City [2016060101010050]
  3. SinoAfrica Joint Center [SAJC201605]

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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.

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