Cytomegalovirus infection blocks apoptosis in cancer cells

Michaelis, Martin; Kotchetkov, Rouslan; Vogel, Jens‐Uwe; Činátl, Jindřich

doi:10.1007/s00018-004-3417-4

Cited by 26 publications

(16 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies from this laboratory and others have also demonstrated that HCMV infection can cause severe endothelial dysfunction, e.g. dysregulated apoptosis (Kovacs et al, 1996;Reboredo et al, 2004;Shen et al, 2004) and hampered apoptosis in HeLa cells (Zhu et al, 1995), cancer cells (Michaelis et al, 2004) and fibroblasts (Reboredo et al, 2004). We previously reported that p53 is stabilized in the nucleus at the early stage of HCMV infection and becomes sequestrated in the cytoplasm at the later stage of the infection (Kovacs et al, 1996;Wang et al, 2001;Wang et al, 2000).…”

Section: Introductionmentioning

confidence: 91%

Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells

Utama

Shen

Mitchell

et al. 2006

Journal of Cell Science

View full text Add to dashboard Cite

endothelial dysfunction, typically known as dysregulated apoptosis, and aberrant expression and sub-cellular localization of p53, a tumor suppressor that accumulates at the late stage of infection. In this study, we examined three hypotheses that could be responsible for HCMV-induced cytoplasmic p53 accumulation at the later stage of infection: hyperactive nuclear export, cytoplasmic p53 tethering and delayed p53 degradation. Leptomycin B treatment, a nuclear export inhibitor, was unable to reduce cytoplasmic p53, thereby eliminating the hyperactive nuclear export mechanism. The findings that nascent p53 still entered nuclei after the nuclear export inhibition indicated that cytoplasmic tethering may play a minor role.Cytoplasmic p53 was still observed after the translation activities were blocked by cycloheximide. There was more than an eight-fold increase in the cytoplasmic p53 half-life with abnormal p53 ubiquitination. Taken together, these results suggest that delayed degradation could be responsible for the cytoplasmic p53 accumulation. The general slow-down of the proteasomal activity and the dysregulated p53 ubiquitination process at the later stage of infection could contribute to the reduced cytoplasmic p53 degradation and might be relevant to dysregulated endothelial apoptosis. The HCMV-induced changes in p53 dynamics could contribute to endothelial dysfunction.

show abstract

Section: Introductionmentioning

confidence: 91%

Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells

Utama

Shen

Mitchell

et al. 2006

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…52 In addition, HCMV has been reported to induce the antiapoptotic cellular proteins AKT, Bcl-2, and Np73. 53 Clearly, these observations indicate that blocking cellular apoptosis is an essential characteristic of the virus. Therefore, one explanation for the HCMV induction of IL-6-mediated antiapoptosis described in this report is that this pathway may represent a redundant mechanism for the virus to maintain cellular survival of persistently HCMV-infected ECs.…”

Section: Il-6 In Hcmv Secretome Induces Angiogenesis 359mentioning

confidence: 99%

IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin

Botto¹,

Streblow²,

DeFilippis³

et al. 2011

Blood

View full text Add to dashboard Cite

“…It also is a leading viral cause of birth defects (7). HCMV infection triggers a series of cellular responses and modulates normal cellular functions, including initiating signal transduction pathways, alternating cell cycle controls, preventing apoptosis, and allowing escape from the immune system (8,14,19,22,27,45).…”

Section: Human Cytomegalovirus (Hcmv) Infection Directly Initiates a mentioning

confidence: 99%

Two Gamma Interferon-Activated Site-Like Elements in the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer Are Important for Viral Replication

Netterwald¹,

Yang²,

Wang³

et al. 2005

J Virol

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) infection directly initiates a signal transduction pathway that leads to activation of a large number of cellular interferon-stimulated genes (ISGs). Our previous studies demonstrated that two interferon response elements, the interferon-stimulated response element and gamma interferonactivated site (GAS), in the ISG promoters serve as HCMV response sites (VRS). Interestingly, two GAS-like VRS elements (VRS1) were also present in the HCMV major immediate-early promoter-enhancer (MIEP/E). In this study, the importance of these VRS elements in viral replication was investigated. We demonstrate that the expression of the major IE genes, IE1 and IE2, is interferon inducible. To understand the biological significance of this signal transduction pathway in HCMV major IE expression, the two VRS1 in the MIEP/E were mutated. Mutant HCMVs in which the VRS elements were deleted or that contained point mutations grew dramatically more slowly than wild-type virus at a low multiplicity of infection (MOI). Insertion of wild-type VRS1 into the mutant viral genome rescued the slow growth phenotype. Furthermore, the expression levels of major IE RNAs and proteins were greatly reduced during infection with the VRS mutants at a low MOI. HCMV microarray analysis indicated that infection of host cells with the VRS mutant virus resulted in a global reduction in the expression of viral genes. Collectively, these data demonstrate that the two VRS elements in the MIEP/E are necessary for efficient viral gene expression and replication. This study suggests that although the HCMV-initiated signal transduction pathway results in induction of cellular antiviral genes, it also functions to stimulate viral major IE gene expression. This might be a new viral strategy in which the pathway is used to regulate gene expression and play a role in reactivation.

show abstract

Cytomegalovirus infection blocks apoptosis in cancer cells

Cited by 26 publications

References 98 publications

Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells

Mechanisms for human cytomegalovirus-induced cytoplasmic p53 sequestration in endothelial cells

IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin

Two Gamma Interferon-Activated Site-Like Elements in the Human Cytomegalovirus Major Immediate-Early Promoter/Enhancer Are Important for Viral Replication

Contact Info

Product

Resources

About