Giant seaperch iridovirus infection upregulates Bas and Bak expression, leading to apoptotic death of fish cells

Chen, Xin Yu; Wen, Chiu-Ming; Hui, Cho-Fat; Chen, Ming Chyuan; Wu, Jen Leih; Hsueh, Tsai Ching; Lei, Wei Han; Hong, Jiann Ruey

doi:10.1016/j.fsi.2015.06.003

Cited by 10 publications

(5 citation statements)

References 61 publications

(47 reference statements)

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“…Apoptosis is an typical outcome following infection by most viruses [32]. For iridovirus, several studies have shown that they can induce apoptosis in their host cells [17,25,32]. Likewise, in our present study, microscopy and flow cytometry revealed typical apoptosis in GSIV-infected GSM cells, accompanied by dramatic reduction in cell volume, DNA fragmentation, and exposure of phosphatydylserine on the outer leaflet of the plasma membrane.…”

Section: Discussionsupporting

confidence: 81%

“…Iridoviruses, including epizootic hematopoietic virus, frog virus 3, red sea bream iridovirus, lymphocystis disease virus, and Chilo iridescent virus can induce apoptosis in their host cells [19][20][21][22][23]. A previous study showed that giant seaperch iridovirus induces apoptotic cell death through up-regulation of the pro-apoptotic genes Bax and Bak in a grouper fin cell line [17]. Mitochondrion-mediated apoptosis and mitochondrial fragmentation occurred during Rana grylio virus infection in fish cells [24].…”

Section: Introductionmentioning

confidence: 99%

“…Iridovirus belongs to the genus Ranavirus in the family Iridoviridae that displays icosahedral symmetry with a 120-200 nm diameter [15]. It has been reported recently that iridoviruses are able to infect lower vertebrates and invertebrates, leading to huge economic losses in aquaculture [16][17][18]. Iridoviruses, including epizootic hematopoietic virus, frog virus 3, red sea bream iridovirus, lymphocystis disease virus, and Chilo iridescent virus can induce apoptosis in their host cells [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chinese Giant Salamander (Andrias davidianus) Iridovirus Infection Leads to Apoptotic Cell Death through Mitochondrial Damage, Caspases Activation, and Expression of Apoptotic-Related Genes

Jiang

Fan

et al. 2019

IJMS

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Chinese giant salamander iridovirus (GSIV) is the causative pathogen of Chinese giant salamander (Andrias davidianus) iridovirosis, leading to severe infectious disease and huge economic losses. However, the infection mechanism by GSIV is far from clear. In this study, a Chinese giant salamander muscle (GSM) cell line is used to investigate the mechanism of cell death during GSIV infection. Microscopy observation and DNA ladder analysis revealed that DNA fragmentation happens during GSIV infection. Flow cytometry analysis showed that apoptotic cells in GSIV-infected cells were significantly higher than that in control cells. Caspase 8, 9, and 3 were activated in GSIV-infected cells compared with the uninfected cells. Consistently, mitochondria membrane potential (MMP) was significantly reduced, and cytochrome c was released into cytosol during GSIV infection. p53 expression increased at an early stage of GSIV infection and then slightly decreased late in infection. Furthermore, mRNA expression levels of pro-apoptotic genes participating in the extrinsic and intrinsic pathway were significantly up-regulated during GSIV infection, while those of anti-apoptotic genes were restrained in early infection and then rose in late infection. These results collectively indicate that GSIV induces GSM apoptotic cell death involving mitochondrial damage, caspases activation, p53 expression, and pro-apoptotic molecules up-regulation.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chinese Giant Salamander (Andrias davidianus) Iridovirus Infection Leads to Apoptotic Cell Death through Mitochondrial Damage, Caspases Activation, and Expression of Apoptotic-Related Genes

Jiang

Fan

et al. 2019

IJMS

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“…Proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electro blotted and then subjected to immunodetection, as previously described [ 28 ]. The membranes were incubated with a dilution of anti-mouse Bax MAb (1:1000; BD Biosciences, San Jose, CA, USA) [ 22 ], anti-mouse Bak antibody (BD Biosciences) [ 22 ], anti-mouse Bcl-2 antibody (BD Biosciences) [ 18 ] anti-mouse Bcl-xL antibody (BD Biosciences) [ 18 ], anti-mouse caspase-3 MAb (1:1000, BD Biosciences), anti-mouse caspase-9, anti-mouse ß-actin MAb (1:2,500; Chemicon, Temecula, CA, USA), and a dilution of an appropriate secondary antibody (1:7500 to 1:10,000) that included peroxidase-labeled goat anti-mouse (Amersham, Piscataway, NJ, USA) and goat anti-rabbit (Amersham) antibodies. Chemiluminescence detection was performed using a Western Exposure Chemiluminescence Kit (Amersham), according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…In studying the mechanism of cell death, we found that the upregulated, de novo-synthesized Bax and Bak proteins formed heterodimers. This upregulation process correlated with a mitochondrial membrane potential (MMP) loss, increased caspase-3 activity, and increased apoptotic cell death [ 5 , 18 ]. Recently, iridoviruses have been shown to induce cell death including typical apoptotic and non-apoptotic cell death [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Infectious Spleen and Kidney Necrosis Virus (ISKNV) Triggers Mitochondria-Mediated Dynamic Interaction Signals via an Imbalance of Bax/Bak over Bcl-2/Bcl-xL in Fish Cells

Chen

Hsueh

et al. 2022

Viruses

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The molecular pathogenesis of infectious spleen and kidney necrosis virus (ISKNV) infections is important but has rarely been studied in connection to host organelle behavior. In the present study, we demonstrated that ISKNV can induce host cell death via a pro-apoptotic Bcl-2 and anti-apoptotic Bcl-2 family member imbalance in mitochondrial membrane potential (MMP or ΔΨm) regulation in GF-1 cells. The results of our study on ISKNV infection showed that it can induce host cell death by up to 80% at day 5 post-infection. Subsequently, in an apoptotic assay, ISKNV infection was seen to induce an increase in Annexin-V-positive signals by 20% and in propidium iodide (PI) staining-positive signals by up to 30% at day 5 (D5) in GF-1 cells. Then, through our studies on the mechanism of cell death in mitochondria function, we found that ISKNV can induce MMP loss by up to 58% and 78% at days 4 and 5 with a JC1 dye staining assay. Furthermore, we found that pro-apoptotic members Bax and Bak were upregulated from the early replication stage (day one) to the late stage (day 5), but the expression profiles were very dynamically different. On the other hand, by Western blotted analysis, the anti-apoptotic members Bcl-2 and Bcl-xL were upregulated very quickly at the same time from day one (two-fold) and continued to maintain this level at day five. Finally, we found that pro-apoptotic death signals strongly activated the downstream signals of caspase-9 and -3. Taken together, these results suggest that ISKNV infection can induce Bax/Bak-mediated cell death signaling downstream of caspase-9 and -3 activation. During the viral replication cycle with the cell death induction process, the anti-apoptotic members Bcl-2/Bcl-xL interacted with the pro-apoptotic members Bax/Bak to maintain the mitochondrial function in the dynamic interaction so as to maintain the MMP in GF-1 cells. These findings may provide insights into DNA-virus control and treatment.

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GSIV serine/threonine kinase can induce apoptotic cell death via p53 and pro-apoptotic gene Bax upregulation in fish cells

Reshi

et al. 2016

Apoptosis

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Previous studies have shown that GSIV induces apoptotic cell death through upregulation of the pro-apoptotic genes Bax and Bak in Grouper fin cells (GF-1 cells). However, the role of viral genome-encoded protein(s) in this death process remains unknown. In this study, we demonstrated that the Giant seaperch iridovirus (GSIV) genome encoded a serine/threonine kinase (ST kinase) protein, and induced apoptotic cell death via a p53-mediated Bax upregulation approach and a downregulation of Bcl-2 in fish cells. The ST kinase expression profile was identified through Western blot analyses, which indicated that expression started at day 1 h post-infection (PI), increased up to day 3, and then decreased by day 5 PI. This profile indicated the role of ST kinase expression during the early and middle phases of viral replication. We then cloned the ST kinase gene and tested its function in fish cells. The ST kinase was transiently expressed and used to investigate possible novel protein functions. The transient expression of ST kinase in GF-1 cells resulted in apoptotic cell features, as revealed with Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) assays and Hoechst 33258 staining at 24 h (37 %) and 48 h post-transfection (PT) (49 %). Then, through studies on the mechanism of cell death, we found that ST kinase overexpression could upregulate the anti-stress gene p53 and the pro-apoptotic gene Bax at 48 h PT. Interestingly, this upregulation of p53 and Bax also correlated to alterations in the mitochondria function that induced loss of mitochondrial membrane potential (MMP) and activated the initiator caspase-9 and the effector caspase-3 in the downstream. Moreover, when the p53-dependent transcriptional downstream gene was blocked by a specific transcriptional inhibitor, it was found that pifithrin-α not only reduced Bax expression, but also averted cell death in GF-1 cells during the ST kinase overexpression. Taken altogether, these results suggested that aquatic GSIV ST kinase could induce apoptosis via upregulation of p53 and Bax expression, resulting in mitochondrial disruption, which activated a downstream caspases-mediated cell death pathway.

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Giant seaperch iridovirus infection upregulates Bas and Bak expression, leading to apoptotic death of fish cells

Cited by 10 publications

References 61 publications

Chinese Giant Salamander (Andrias davidianus) Iridovirus Infection Leads to Apoptotic Cell Death through Mitochondrial Damage, Caspases Activation, and Expression of Apoptotic-Related Genes

Chinese Giant Salamander (Andrias davidianus) Iridovirus Infection Leads to Apoptotic Cell Death through Mitochondrial Damage, Caspases Activation, and Expression of Apoptotic-Related Genes

Infectious Spleen and Kidney Necrosis Virus (ISKNV) Triggers Mitochondria-Mediated Dynamic Interaction Signals via an Imbalance of Bax/Bak over Bcl-2/Bcl-xL in Fish Cells

GSIV serine/threonine kinase can induce apoptotic cell death via p53 and pro-apoptotic gene Bax upregulation in fish cells

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