Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

Cheng, Shuang; Jiang, Xuan; Yang, Bo; Wen, Lei; Zhao, Fei; Zeng, Wen‐Bo; Liu, Xi-Juan; Xiao, Dong; Sun, Jinyan; Ming, Yingzi; Zhu, Hua; Rayner, Simon; Tang, Qiyi; Fortunato, Elizabeth A.; Luo, Min‐Hua

doi:10.1016/j.virol.2017.07.023

Cited by 10 publications

(8 citation statements)

References 66 publications

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“…Human cytomegalovirus (HCMV) components have been found to be present in a large proportion of glioblastoma (GBM) (Cobbs et al, 2002). HCMV establishes latency in T98G glioblastoma cells and latent HCMV can be reactivated (Cheng et al, 2017). It was also reported that HCMV potentially induces a functional mesenchymal-to-epithelial (MET) transition without affecting their viability in transformed breast carcinoma and glioma stem cells, which might encourage tumor colonization (Oberstein and Shenk 2017).…”

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confidence: 99%

Human cytomegalovirus DNA and immediate early protein 1/2 are highly associated with glioma and prognosis

et al. 2020

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confidence: 99%

Human cytomegalovirus DNA and immediate early protein 1/2 are highly associated with glioma and prognosis

et al. 2020

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“…In this regard we decided to verify their expression in a GBM cell line. Previous studies have shown that established GBM cells, with different degrees of differentiation, exhibit different levels of permissiveness to HCMV infection and replication [ 45 – 51 ]. In these cells, the kinetics of protein expression is delayed, and low numbers of progeny viruses are produced [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor

et al. 2022

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The human cytomegalovirus (HCMV) UL111A gene encodes several homologs of the cellular interleukin 10 (cIL-10). Alternative splicing in the UL111A region produces two relatively well-characterized transcripts designated cmvIL-10 (isoform A) and LAcmvIL-10 (isoform B). The cmvIL-10 protein is the best characterized, both structurally and functionally, and has many immunosuppressive activities similar to cIL-10, while LAcmvIL-10 has more restricted biological activities. Alternative splicing also results in five less studied UL111A transcripts encoding additional proteins homologous to cIL-10 (isoforms C to G). These transcripts were identified during productive HCMV infection of MRC-5 cells with the high passage laboratory adapted AD169 strain, and the structure and properties of the corresponding proteins are largely unknown. Moreover, it is unclear whether these protein isoforms are able to bind the cellular IL-10 receptor and induce signalling. In the present study, we investigated the expression spectrum of UL111A transcripts in fully permissive MRC-5 cells and semi permissive U251 cells infected with the low passage HCMV strain TB40E. We identified a new spliced transcript (H) expressed during productive infection. Using computational methods, we carried out molecular modelling studies on the three-dimensional structures of the HCMV IL-10 proteins encoded by the transcripts detected in our work (cmvIL-10 (A), LAcmvIL-10 (B), E, F and H) and on their interaction with the human IL-10 receptor (IL-10R1). The modelling predicts clear differences between the isoform structures. Furthermore, the in silico simulations (molecular dynamics simulation and normal-mode analyses) allowed us to evaluate regions that contain potential receptor binding sites in each isoform. The analyses demonstrate that the complexes between the isoforms and IL-10R1 present different types of molecular interactions and consequently different affinities and stabilities. The knowledge about structure and expression of specific viral IL-10 isoforms has implications for understanding of their properties and role in HCMV immune evasion and pathogenesis.

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“…It is important to choose proper cell types and strains to establish a cell model for cross-species infection of HCMV. In human, primary fibroblasts with skin or lung origin are mostly used to study in vitro HCMV infection because it is one of the main target cell types, easy to culture, permissive for all strains, and supports production of high titer of cell-free virus [20]. Towne strain, one of the mostly used laboratory strain, has been reported to be permissive for HCMV infection of CF.…”

Section: Discussionmentioning

confidence: 99%

Primary Tree Shrew Dermis Fibroblasts Support Lytic Replication of Human Cytomegalovirus

Dong¹,

Jiao²,

Yang³

et al. 2018

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As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 10 3 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

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Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

Cited by 10 publications

References 66 publications

Human cytomegalovirus DNA and immediate early protein 1/2 are highly associated with glioma and prognosis

Human cytomegalovirus DNA and immediate early protein 1/2 are highly associated with glioma and prognosis

Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor

Primary Tree Shrew Dermis Fibroblasts Support Lytic Replication of Human Cytomegalovirus

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