Viral protein synthesis is required for Enterovirus 71 to induce apoptosis in human glioblastoma cells

Shih, Shin‐Ru; Weng, Kuo-Feng; Stollar, Victor; Li, Meiling

doi:10.1080/13550280701798980

Cited by 47 publications

(34 citation statements)

References 39 publications

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“…Apoptosis-inducing viruses of the family Bunyaviridae like Oropouche virus, Crimean-Congo hemorrhagic fever virus or hantavirus show comparable time-courses for the induction of apoptosis (Acrani et al, 2010;Karlberg et al, 2011), and for these viruses it was shown that apoptosis of the host cell was not induced by binding or entry of the virus but by viral replication (Acrani et al, 2010;Li et al, 2004;Rodrigues et al, 2012). Similarly, experiments with UV-inactivated viruses such as West Nile virus, Newcastle disease virus, Oropouche virus and enterovirus have also identified a dependence on viral replication as the major apoptosis-inducing factor (Acrani et al, 2010;Kleinschmidt et al, 2007;Ravindra et al, 2008;Shih et al, 2008). The late onset of TCRV-induced apoptosis indicated that downstream steps in virus replication (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis can be initiated via the extrinsic pathway, mediated by death receptors of the TNF-family on the cell surface (Ashkenazi & Dixit, 1998), as well as the intrinsic pathway, triggered by the release of cytochrome c from the inner mitochondrial membrane into the cytosol (Granville & Gottlieb, 2002). Virusinduced apoptosis can be mediated via the extrinsic as well as the intrinsic signalling pathways, and is most often initiated by viral replication/transcription and the accumulation of viral RNA and proteins in the cytoplasm of the host cell, as demonstrated for infections with West Nile virus, Newcastle disease virus, Oropouche virus and enterovirus (Acrani et al, 2010;Kleinschmidt et al, 2007;Ravindra et al, 2008;Shih et al, 2008). Both signalling pathways converge to proteolytically activate a cascade of cysteine-dependent aspartate-specific proteases (caspases) that are present as inactive pro-caspases in all cells.…”

Section: Introductionmentioning

confidence: 99%

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The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells

Wolff

Groseth

Meyer

et al. 2016

Journal of General Virology

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The Arenaviridae is a diverse and growing family of viruses that already includes more than 25 distinct species. While some of these viruses have a significant impact on public health, others appear to be non-pathogenic. At present little is known about the host cell responses to infection with different arenaviruses, particularly those found in the New World; however, apoptosis is known to play an important role in controlling infection of many viruses. Here we show that infection with Tacaribe virus (TCRV), which is widely considered the prototype for non-pathogenic arenaviruses, leads to stronger induction of apoptosis than does infection with its human-pathogenic relative Junín virus. TCRV-induced apoptosis occurred in several cell types during late stages of infection and was shown to be caspase-dependent, involving the activation of caspases 3, 7, 8 and 9. Further, UV-inactivated TCRV did not induce apoptosis, indicating that the activation of this process is dependent on active viral replication/transcription. Interestingly, when apoptosis was inhibited, growth of TCRV was not enhanced, indicating that apoptosis does not have a direct negative effect on TCRV infection in vitro. Taken together, our data identify and characterize an important virus-host cell interaction of the prototypic, non-pathogenic arenavirus TCRV, which provides important insight into the growing field of arenavirus research aimed at better understanding the diversity in responses to different arenavirus infections and their functional consequences.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells

Wolff

Groseth

Meyer

et al. 2016

Journal of General Virology

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“…FBP2 is a substrate of caspase (56). EV71 infection induces caspase activation (46,57). A pan-caspase inhibitor, QVD-OPh, was used to determine whether EV71-induced caspase activity is involved in FBP2 truncation.…”

Section: Ev71 Infection Induces Fbp2 Truncationmentioning

confidence: 99%

Enterovirus 71 Infection Cleaves a Negative Regulator for Viral Internal Ribosomal Entry Site-Driven Translation

Chen

Kung

Weng

et al. 2013

J Virol

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Far-upstream element-binding protein 2 (FBP2) is an internal ribosomal entry site (IRES) trans-acting factor (ITAF) that negatively regulates enterovirus 71 (EV71) translation. This study shows that EV71 infection cleaved FBP2. Live EV71 and the EV71 replicon (but not UV-inactivated virus particles) induced FBP2 cleavage, suggesting that viral replication results in FBP2 cleavage. The results also showed that virus-induced proteasome, autophagy, and caspase activity co-contribute to EV71-induced FBP2 cleavage. Using FLAG-fused FBP2, we mapped the potential cleavage fragments of FBP2 in infected cells. We also found that FBP2 altered its function when its carboxyl terminus was cleaved. This study presents a mechanism for virus-induced cellular events to cleave a negative regulator for viral IRES-driven translation. Enterovirus 71 (EV71), an RNA virus that belongs to the family Picornaviridae, has caused several outbreaks worldwide and often results in severe neurological complications and high mortality in patients (1-10). Picornavirus infection can affect host mechanisms, such as host cap-dependent translation (11, 12), transcription (13,14), and immune responses (15-17). FBP2, also called the KH-type splicing regulatory protein (KSRP), was first identified as a single-strand DNA-binding protein (37). FBP2 positively regulates c-myc transcription (37), enhances the splicing of the neuron-specific c-src N1 exon (38, 39), edits apolipoprotein B (apoB) mRNA (40), and is associated with mRNA decay (41,42). FBP2 is also a component of the Dicer and Drosha complexes and regulates let-7 microRNA (miRNA) biogenesis (43-45). A previous study has shown that FBP2 binds to the EV71 5= untranslated region (UTR), which contains an IRES, and downregulates IRES activity by competing with other, positive ITAFs, such as PTB (35).In this study, we show that FBP2, a negative ITAF of EV71, is cleaved in EV71-infected cells. We also demonstrate that EV71-induced caspase activity, autophagic activity, and proteasome activity are involved in virus-induced cleavage of FBP2. Moreover, we found a cleavage product, FBP2 , that loses its carboxyl terminus and positively regulates the IRES activity of EV71. MATERIALS AND METHODS Cell lines and virus infection.Human embryonal rhabdomyosarcoma (RD) and HeLa cells were maintained in Dulbecco's modified Eagle medium (DMEM) (GIBCO) containing 10% fetal bovine serum (FBS; GIBCO) at 37°C. RD cells were grown to 80% to 90% confluence and were infected with enterovirus 71 strain Tainan/4643/98 at a multiplicity of infection (MOI) of 40 PFU per cell in serum-free DMEM. Virus was adsorbed at 37°C for 1 h. After adsorption, the cells were washed with phosphate-buffered saline (PBS) and were incubated with a medium containing 2% FBS. In several experiments, RD cells were infected with EV71 for 1 h, washed with PBS, and incubated with a medium containing 2% FBS and various inhibitors. UV-inactivated EV71 was prepared by following a method described elsewhere (46). In other experiments, RD cells were tran...

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“…Since then, a wealth of data has been accumulated that shows that the activation of apoptotic pathways is a widespread, though not universal, response to picornavirus infection. Thus, apoptosis-inducing capacity was reported for coxsackieviruses B3, B4, and B5 (22,54,82), enteroviruses 70 and 71 (25,27,60,88), human rhinoviruses 1B, 9, 14, and 16 (32,92,100), foot-and-mouth disease virus (53,76), avian encephalomyelitis virus (62,63), and hepatitis A virus (16,43) and was the subject of several recent reviews (15,102). The antiapoptotic activity of picornaviruses was studied predominantly by using poliovirus (3,8,13,72) and coxsackievirus B3 (21,36,85).…”

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confidence: 99%

Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral “Security” Protein

Romanova

Lidsky

Kolesnikova

et al. 2009

J Virol

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Apoptosis is a common antiviral defensive mechanism that potentially limits viral reproduction and spread. Many viruses possess apoptosis-suppressing tools. Here, we show that the productive infection of HeLa cells with encephalomyocarditis virus (a cardiovirus) was not accompanied by full-fledged apoptosis (although the activation of caspases was detected late in infection) but rather elicited a strong antiapoptotic state, as evidenced by the resistance of infected cells to viral and nonviral apoptosis inducers. The development of the antiapoptotic state appeared to depend on a function(s) of the viral leader (L) protein, since its mutational inactivation resulted in the efflux of cytochrome c from mitochondria, the early activation of caspases, and the appearance of morphological and biochemical signs of apoptosis in a significant proportion of infected cells. Infection with both wild-type and L-deficient viruses induced the fragmentation of mitochondria, which in the former case was not accompanied with cytochrome c efflux. Although the exact nature of the antiapoptotic function(s) of cardioviruses remains obscure, our results suggested that it includes previously undescribed mechanisms operating upstream and possibly downstream of the mitochondrial level, and that L is involved in the control of these mechanisms. We propose that cardiovirus L belongs to a class of viral proteins, dubbed here security proteins, whose roles consist solely, or largely, in counteracting host antidefenses. Unrelated L proteins of other picornaviruses as well as their highly variable 2A proteins also may be security proteins. These proteins appear to be independent acquisitions in the evolution of picornaviruses, implying multiple cases of functional (though not structural) convergence.

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Viral protein synthesis is required for Enterovirus 71 to induce apoptosis in human glioblastoma cells

Cited by 47 publications

References 39 publications

The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells

The New World arenavirus Tacaribe virus induces caspase-dependent apoptosis in infected cells

Enterovirus 71 Infection Cleaves a Negative Regulator for Viral Internal Ribosomal Entry Site-Driven Translation

Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral “Security” Protein

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