Interaction des virus avec la voie cellulaire de réponse à l’hypoxie

Pillet, Sylvie; Guyader, N. Le

doi:10.1051/medsci/2005215517

Cited by 2 publications

(3 citation statements)

References 21 publications

(27 reference statements)

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“…For example, HIF-1α has also been implicated in viral oncogenesis [38]. Perhaps one of the most studied viruses in association to the HIF-1α machinery is the Kaposi’s sarcoma-associated herpes virus (KSHV) [5, 6, 9, 20].…”

Section: Discussionmentioning

confidence: 99%

“…KSHV is able to stabilize HIF-1α through phosphorylation by MAP kinases and PI3/Akt, and to force HIF-1α to bind to HREs found in the viral genome, stimulating the formation of new virions [53]. However, the secondary activation of HIF-1α by HHV-8 also induces the transcription of VEGF and other factors that promote endothelial cell proliferation and may facilitate the progression of Kaposi sarcoma [5, 6, 9, 20, 38]. In a similar way, hepatitis B virus (HBV) [35, 62, 63], hepatitis C virus (HCV) [36], Epstein–Barr virus (EBV) [24, 28, 57] and recently, the human T-cell leukemia virus-1 (HTLV-1) [55] can stabilize HIF-1α and utilize this protein either to complete their lytic cycle or to facilitate tumor progression as well as intra-tumoral neo-angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia inducible factor-1 alpha activation of the JCV promoter: role in the pathogenesis of Progressive Multifocal Leukoencephalopathy

2009

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Activation of viral promoter transcription is a crucial event in the life cycle of several viruses. Hypoxia inducible factor-1 alpha (HIF-1α) is an inducible transcription factor whose activity is dependent on environmental conditions, most notably oxygen levels and cellular stress. HIF-1α has been implicated in the pathogenesis of several viruses, including HIV-1, HHV-8 and RSV. Under hypoxic conditions or oxidative stress, HIF-1α becomes stable and translocates to the nucleus, where it modulates gene transcription. The objective of the present study was to investigate a possible role for HIF-1α in the activation of JCV. Glial cell cultures infected with JCV demonstrated a significant increase in the levels of HIF-1α, in where it is located to the nucleus. Immunohistochemical studies corroborated upregulation of HIF-1α in JCV infected oligodendrocytes and astrocytes in clinical samples of PML compared with normal glial cells from the same samples in which HIF-1α expression is weak. CAT assays performed in co-transfected glial cells demonstrated activation of the JCV early promoter in the presence of HIF-1α. This activation was potentiated in the presence of Smad3 and Smad4. Finally, chromatin immunoprecipitation assays demonstrated the binding of HIF-1α to the JCV control region. These results suggest a role for HIF-1α in the activation of JCV; understanding of this pathway may lead to the development of more effective therapies for PML, thus far an incurable disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypoxia inducible factor-1 alpha activation of the JCV promoter: role in the pathogenesis of Progressive Multifocal Leukoencephalopathy

2009

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“…Moreover, increased expression and amplification have been shown for the human erythrovirus B19 virus (Caillet-Fauquet et al, 2004;Pillet et al, 2004). As opposed to what had been suggested by Pillet & Le Guyader (2005), the production of vectors based on the parvovirus MVM(p) was reduced in hypoxia compared with 20 % O 2 tension. It is difficult to ascertain which step of the viral life cycle is blocked in hypoxia, as the mechanisms governing MVM amplification are not yet fully elucidated.…”

Section: Mvm(p)mentioning

confidence: 97%

Hypoxic-response elements in the oncolytic parvovirus Minute virus of mice do not allow for increased vector production at low oxygen concentration

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Caillet-Fauquet

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et al. 2006

Journal of General Virology

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Vectors derived from the autonomous parvovirus Minute virus of mice, MVM(p), are promising tools for the gene therapy of cancer. The validation of their in vivo anti-tumour effect is, however, hampered by the difficulty to produce high-titre stocks. In an attempt to increase vector titres, host cells were subjected to low oxygen tension (hypoxia). It has been shown that a number of viruses are produced at higher titres under these conditions. This is the case, among others, for another member of the family Parvoviridae, the erythrovirus B19 virus. Hypoxia stabilizes a hypoxia-inducible transcription factor (HIF-1a) that interacts with a 'hypoxia-responsive element' (HRE), the consensus sequence of which ( A / G CGTG) is present in the B19 and MVM promoters. Whilst the native P4 promoter was induced weakly in hypoxia, vector production was reduced dramatically, and adding HRE elements to the P4 promoter of the vector did not alleviate this reduction. Hypoxia has many effects on cell metabolism. Therefore, even if the P4 promoter is activated, the cellular factors that are required for the completion of the parvoviral life cycle may not be expressed.The parvovirus Minute virus of mice, MVM(p), replicates preferentially in oncogenic-transformed cells, where it completes a lytic life cycle (Rommelaere & Cornelis, 1991). This property is exploited in gene-therapy vectors derived from autonomous parvoviruses (Russell et al., 1992;Cornelis et al., 2004). The MVM(p) genome is composed of two transcription units, encoding two sets of viral proteins, NS (non-structural) and VP (capsid), under the control of the P4 and P38 promoters, respectively (Cotmore et al., 1983). The non-structural protein NS1 plays an important role in viral DNA replication (Nüesch et al., 1998), is toxic in transformed cells (Caillet-Fauquet et al., 1990) and is required for transactivation of the P38 promoter, which is otherwise only expressed at a very low basal level (Rhode, 1985).The mechanisms underlying the preferential expression of MVM(p) in transformed cells are only poorly understood, but it is at least in part linked to the upregulation of the P4 promoter in these cells compared with normal cells. We therefore wanted to determine whether P4 activity could be further enhanced and whether this could improve vector production. We have explored the possibility of producing MVM vectors under low oxygen tension (hypoxia). Gene expression and production of the human erythrovirus B19 virus are increased under these conditions (Caillet-Fauquet et al., 2004;Pillet et al., 2004). Regulation of promoter activity in hypoxia occurs through the interaction of the transcriptional regulator hypoxia-inducible factor (HIF-1) with a 'hypoxia-responsive element' (HRE) (Semenza, 2001). The MVM(p) promoter contains four putative HREs (consensus sequence A / G CGTG), two in each of the sense and antisense orientations.The presence of the HRE in the promoter region is necessary, but not sufficient, for promoter regulation. Other cellular elements are probably...

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Interaction des virus avec la voie cellulaire de réponse à l’hypoxie

Cited by 2 publications

References 21 publications

Hypoxia inducible factor-1 alpha activation of the JCV promoter: role in the pathogenesis of Progressive Multifocal Leukoencephalopathy

Hypoxia inducible factor-1 alpha activation of the JCV promoter: role in the pathogenesis of Progressive Multifocal Leukoencephalopathy

Hypoxic-response elements in the oncolytic parvovirus Minute virus of mice do not allow for increased vector production at low oxygen concentration

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