Influence of Doxorubicin and Etoposide on the CD 95 Mediated Apoptosis in EBV Infected Lymphoma Cells BL-41 and DG-75

Zagorodnya, Svіtlana; Baranova, G.V.; Nesterova, N. V.

doi:10.15407/microbiolj77.04.069

Cited by 1 publication

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HeLa cells were cotransfected with PinX1 or the G51A PinX1 mutant along with 3C or treated with 25 M etoposide. Etoposide is a DNA-damaging reagent and induces apoptosis in a variety of cell lines (35)(36)(37)(38). The apoptosis was measured by annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) staining and terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling (TUNEL) staining.…”

Section: Resultsmentioning

confidence: 99%

Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein

Yao

et al. 2017

J Virol

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is an emerging pathogen causing hand, foot, and mouth disease (HFMD) and fatal neurological diseases in infants and young children due to their underdeveloped immunocompetence. EV71 infection can induce cellular apoptosis through a variety of pathways, which promotes EV71 release. The viral protease 3C plays an important role in EV71-induced apoptosis. However, the molecular mechanism responsible for 3C-triggered apoptosis remains elusive. Here, we found that EV71 3C directly interacted with PinX1, a telomere binding protein. Furthermore, 3C cleaved PinX1 at the site of Q50-G51 pair through its protease activity. Overexpression of PinX1 reduced the level of EV71-induced apoptosis and EV71 release, whereas depletion of PinX1 by small interfering RNA promoted apoptosis induced by etoposide and increased EV71 release. Taken together, our study uncovered a mechanism that EV71 utilizes to promote host cell apoptosis through cleavage of cellular protein PinX1 by 3C.IMPORTANCE EV71 3C plays an important role in processing viral proteins and interacting with host cells. In this study, we showed that 3C promoted apoptosis through cleaving PinX1, a telomere binding protein, and that this cleavage facilitated EV71 release. Our study demonstrated that PinX1 plays an important role in EV71 release and revealed a novel mechanism that EV71 utilizes to induce apoptosis. This finding is important in understanding EV71-host cell interactions and has potential impact on understanding other enterovirus-host cell interactions.KEYWORDS enterovirus 71, 3C, PinX1, apoptosis E nterovirus 71 (EV71) is an emerging pathogen that was originally isolated from an infant with central nervous system disease in California (1). Since then, EV71 has caused several large-scale epidemic outbreaks throughout the world, especially in the Asia-Pacific region (2-4). These outbreaks caused significant morbidity and mortality and severely endangered the public health (5). EV71 infection causes hand, foot, and mouth disease (HFMD) and fatal neurological diseases, such as aseptic meningitis, brainstem encephalitis, and neurogenic pulmonary edema (NPE), in infants and young children due to their underdeveloped immunocompetence (6). To date, there are no effective therapeutic medicines or vaccines for EV71.EV71 belongs to the Picornaviridae family with a single positive-stranded RNA genome. Translation of the RNA genome produces a single polyprotein precursor that is subsequently processed into structural (VP1, VP2, VP3, and VP4) and nonstructural (2A, 2B, 2C, 3A, 3B, 3C, and 3D) proteins (7). In addition to its role in viral precursor processing (8), 3C is also involved in a number of biological processes. It has been reported that 3C cleaves cellular CstF-64 protein, which inhibits host RNA processing and polyadenylation (9). Interferon-regulatory factor 7 (IRF7) (10), TIR domain-containing adaptor inducing beta interferon (TRIF) (11) and the TAK1/TAB1/

show abstract

Section: Resultsmentioning

confidence: 99%

Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein

Yao

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

Influence of Doxorubicin and Etoposide on the CD 95 Mediated Apoptosis in EBV Infected Lymphoma Cells BL-41 and DG-75

Cited by 1 publication

References 8 publications

Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein

Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein

Contact Info

Product

Resources

About