Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

TY - JOUR

T1 - Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

AU - Cheng, Shuang

AU - Jiang, Xuan

AU - Yang, Bo

AU - Wen, Le

AU - Zhao, Fei

AU - Zeng, Wen Bo

AU - Liu, Xi Juan

AU - Dong, Xiao

AU - Sun, Jin Yan

AU - Ming, Ying Zi

AU - Zhu, Hua

AU - Rayner, Simon

AU - Tang, Qiyi

AU - Fortunato, Elizabeth

AU - Luo, Min Hua

N1 - Funding Information: We thank Juan Min and Ding Gao for technical support on the flow cytometry and confocal microscopy. We thank John O'Dowd for critical reading of the manuscript. The study was supported by the National Natural Science Foundation of China (81601770), Applied Basic Research Program of Wuhan City (2016060101010050) and Sino-Africa Joint Center (SAJC201605). Publisher Copyright: © 2017

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Human cytomegalovirus

KW - Latent cell model of brain origin

KW - Latent infection

KW - Reactivation

KW - T98G cells

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U2 - https://doi.org/10.1016/j.virol.2017.07.023

DO - https://doi.org/10.1016/j.virol.2017.07.023

M3 - Article

C2 - 28750324

SN - 0042-6822

VL - 510

SP - 205

EP - 215

JO - Virology

JF - Virology

ER -