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Reddi, Honey V.; Kumar, Romesh; Jain, Swatantra Kumar; Kumar, Vijay

doi:10.1023/a:1024491028647

Cited by 19 publications

(10 citation statements)

References 46 publications

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“…For HBx (Fig. 1A), regions D and E play important roles in signal transduction and transactivation [24,25] and therefore, the shRNAs directed against these regions were termed X‐D and X‐E respectively. The shRNA constructs directed against the transactivation and leucine zipper domains of c‐ myc [26] were called M‐T and M‐Z respectively.…”

Section: Resultsmentioning

confidence: 99%

Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c‐myc by small interfering RNAs

Hung

Kumar

2004

FEBS Letters

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With a view to developing therapeutic strategies against hepatocellular carcinoma (HCC), we have recently shown that co-expression of c-myc and the X protein of hepatitis B virus (HBx) resulted in the development of HCC in the X-myc transgenic mice [Lakhtakia et al., J. Gastroenterol. Hepatol. 18 (2003) 80^91]. We now show in cell culture-based studies that small interfering RNA (siRNA) corresponding to HBx and cmyc can regulate expression and transactivation of the target genes. Expression vectors for small hairpin RNAs (shRNAs) against two di¡erent regions each of the HBx and c-myc open reading frames were constructed and their regulatory e¡ects were investigated in COS-1 cells. A dose-dependent speci¢c inhibition in the expression levels of HBx and c-myc was observed with individual shRNAs. Further, the recombinantly expressed shRNAs also blocked the transactivation functions of their cognate genes. Though each shRNA worked at a di¡erent e⁄-ciency, the inhibitory e¡ects with two di¡erent shRNAs were cumulative. These results appear promising for developing a siRNA-based therapy for HCC. ß 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

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Section: Resultsmentioning

confidence: 99%

Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c‐myc by small interfering RNAs

Hung

Kumar

2004

FEBS Letters

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“…Importantly, CREB is a transcription factor involved in the regulation of glucose homeostasis, growth factor-dependent cell survival, and immune modulation [42] . Furthermore, a pathogenic role for CREB has been demonstrated during HBV pathogenesis; the HBV X protein activates viral gene transcription by interacting with CREB, leading to activation of the HBV enhancer I [69] . CREB can also induce expression of early growth response-1, which facilitates herpes simplex virus-1 replication [70] – [72] .…”

Section: Discussionmentioning

confidence: 99%

Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes

et al. 2014

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BackgroundInterleukin (IL)-10 levels are increased in dengue virus (DENV)-infected patients with severe disorders. A hypothetical intrinsic pathway has been proposed for the IL-10 response during antibody-dependent enhancement (ADE) of DENV infection; however, the mechanisms of IL-10 regulation remain unclear.Principle FindingWe found that DENV infection and/or attachment was sufficient to induce increased expression of IL-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic THP-1 cells and human peripheral blood monocytes. IL-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (CREB), primarily through protein kinase A (PKA)- and phosphoinositide 3-kinase (PI3K)/PKB-regulated pathways, with PKA activation acting upstream of PI3K/PKB. DENV infection also caused glycogen synthase kinase (GSK)-3β inactivation in a PKA/PI3K/PKB-regulated manner, and inhibition of GSK-3β significantly increased DENV-induced IL-10 production following CREB activation. Pharmacological inhibition of spleen tyrosine kinase (Syk) activity significantly decreased DENV-induced IL-10 production, whereas silencing Syk-associated C-type lectin domain family 5 member A caused a partial inhibition. ADE of DENV infection greatly increased IL-10 expression by enhancing Syk-regulated PI3K/PKB/GSK-3β/CREB signaling. We also found that viral load, but not serotype, affected the IL-10 response. Finally, modulation of IL-10 expression could affect DENV replication.SignificanceThese results demonstrate that, in monocytes, IL-10 production is regulated by ADE through both an extrinsic and an intrinsic pathway, all involving a Syk-regulated PI3K/PKB/GSK-3β/CREB pathway, and both of which impact viral replication.

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“…Nucleotide 1653 is also located within the × gene at codon 94. × protein binds and affects several intracellular signal transduction pathways, cell cycle progression, and apoptosis regulation [25]. Codon 94 of × protein is included in area of several transcription factor binding sites, such as CREB, RPB5, TFIIB, XAP-1, C/EBPalpha, and XAP-3.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients

et al. 2011

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BackgroundHepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC.MethodsWe compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced.ResultsAll patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation.ConclusionsG1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development.

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Cited by 19 publications

References 46 publications

Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c‐myc by small interfering RNAs

Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c‐myc by small interfering RNAs

Antibody-Dependent Enhancement Infection Facilitates Dengue Virus-Regulated Signaling of IL-10 Production in Monocytes

Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients

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