Role of cathepsin B in dengue virus-mediated apoptosis

Morchang, Atthapan; Panaampon, Jutatip; Suttitheptumrong, Aroonroong; Yasamut, Umpa; Noisakran, Sansanee; Yenchitsomanus, Pa‐thai; Limjindaporn, Thawornchai

doi:10.1016/j.bbrc.2013.07.009

Cited by 26 publications

(24 citation statements)

References 45 publications

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“…DENV infection induces caspase 3 activity and apoptosis [ 22 , 30 ]. Apoptosis-related gene expression profiling in DENV-infected HepG2 cells [ 31 ] and animal models [ 13 , 14 ] was previously conducted.…”

Section: Discussionmentioning

confidence: 99%

RNAi screen reveals a role of SPHK2 in dengue virus–mediated apoptosis in hepatic cell lines

et al. 2017

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Hepatic dysfunction is a feature of dengue virus (DENV) infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show apoptosis, which relates to the pathogenesis of DENV infection. However, how DENV induced liver injury is not fully understood. In this study, we aim to identify the factors that influence cell death by employing an apoptosis-related siRNA library screening. Our results show the effect of 558 gene silencing on caspase 3-mediated apoptosis in DENV-infected Huh7 cells. The majority of genes that contributed to apoptosis were the apoptosis-related kinase enzymes. Tumor necrosis factor superfamily member 12 (TNFSF12), and sphingosine kinase 2 (SPHK2), were selected as the candidate genes to further validate their influences on DENV-induced apoptosis. Transfection of siRNA targeting SPHK2 but not TNFSF12 genes reduced apoptosis determined by Annexin V/PI staining. Knockdown of SPHK2 did not reduce caspase 8 activity; however, did significantly reduce caspase 9 activity, suggesting its involvement of SPHK2 in the intrinsic pathway of apoptosis. Treatment of ABC294649, an inhibitor of SPHK2, reduced the caspase 3 activity, suggesting the involvement of its kinase activity in apoptosis. Knockdown of SPHK2 significantly reduced caspase 3 activity not only in DENV-infected Huh7 cells but also in DENV-infected HepG2 cells. Our results were consistent across all of the four serotypes of DENV infection, which supports the pro-apoptotic role of SPHK2 in DENV-infected liver cells.

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Section: Discussionmentioning

confidence: 99%

RNAi screen reveals a role of SPHK2 in dengue virus–mediated apoptosis in hepatic cell lines

et al. 2017

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“…To verified the key differential proteins to HCV subgenome replication, HepG2 cells were transfected with 20 nM siRNAs targeted to CTSB [ 34 ] or over-expression plasmids of vimentin, and cells were transfected with HCV 1b RNA using Interferin (Polyplus-transfection Inc, USA) 12 h later and harvested for protein extraction and total mRNA isolation after 24 and 48 h. Non-related control siNC (Genepharma, China) and pcDNA3.1 were used as negative controls.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines

Xin

Han

et al. 2015

PLoS ONE

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Chronic hepatitis C virus (HCV) infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT-PCR. The differential expression of Glutathione S-transferase P (GSTP1), Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), carboxylesterase 1 (CES1), vimentin, Proteasome activator complex subunit1 (PSME1), and Cathepsin B (CTSB) were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication.

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“…For a productive replication cycle leading to lysis of cells, the following aspects are important: (i) attachment and entry into cells; (ii) uncoating by proteases to facilitate escape of the virus from the endosomes; (iii) transcription and replication of viral genomes leading to production of progeny viruses; and (iv) the induction of cell death to release the nascent viruses [ 18 , 19 , 20 , 21 , 22 ]. It has been demonstrated that cathepsin B plays an important role in cell death induction for several viruses [ 23 , 24 , 25 ]. It remains to be established how the cathepsin B downregulation facilitates the persistent reovirus infection.…”

Section: Introductionmentioning

confidence: 99%

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Kemp

Hoeben

Wollenberg

2015

Viruses

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Reoviruses are non-enveloped viruses with a segmented double stranded RNA genome. In humans, they are not associated with serious disease. Human reoviruses exhibit an inherent preference to replicate in tumor cells, which makes them ideally suited for use in oncolytic virotherapies. Their use as anti-cancer agent has been evaluated in several clinical trials, which revealed that intra-tumoral and systemic delivery of reoviruses are well tolerated. Despite evidence of anti-tumor effects, the efficacy of reovirus in anti-cancer monotherapy needs to be further enhanced. The opportunity to treat both the primary tumor as well as metastases makes systemic delivery a preferred administration route. Several pre-clinical studies have been conducted to address the various hurdles connected to systemic delivery of reoviruses. The majority of those studies have been done in tumor-bearing immune-deficient murine models. This thwarts studies on the impact of the contribution of the immune system to the tumor cell eradication. This review focuses on key aspects of the reovirus/host-cell interactions and the methods that are available to modify the virus to alter these interactions. These aspects are discussed with a focus on improving the reovirus’ antitumor efficacy.

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Role of cathepsin B in dengue virus-mediated apoptosis

Cited by 26 publications

References 45 publications

RNAi screen reveals a role of SPHK2 in dengue virus–mediated apoptosis in hepatic cell lines

RNAi screen reveals a role of SPHK2 in dengue virus–mediated apoptosis in hepatic cell lines

Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

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