Direct cleavage of human TATA-binding protein by poliovirus protease 3C in vivo and in vitro.

Clark, Mary C.; Lieberman, Paul M.; Berk, Arnold; Dasgupta, Asim

doi:10.1128/mcb.13.2.1232

Cited by 171 publications

(143 citation statements)

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“…37,38 Similarly, viral proteinase 3C (3C Pro ) has been shown to cleave the host cell transcription binding protein that is involved in initiation of TATA-dependent transcription. 39,40 It is possible that expression of these viral proteins is sufficient to induce a potent direct cytopathic effect on cardiac myocytes by inhibiting both myocyte transcriptional and translational mechanisms. In addition, it is possible that doublestranded viral RNA may be able to activate intracellular signaling mechanisms that contribute to the effect of persistent viral infection on cardiac myocytes.…”

Section: Discussionmentioning

confidence: 99%

Low-Level Expression of a Mutant Coxsackieviral cDNA Induces a Myocytopathic Effect in Culture

et al. 1998

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Background-Enteroviral ribonucleic acids have been identified in heart muscle of a subset of patients with myocarditis and dilated cardiomyopathy as well as in a mouse model of persistent coxsackievirus B3 (CVB3) infection, suggesting that persistent viral infection along with activation of an immune response may contribute to the pathogenesis of ongoing cardiac disease and dilated cardiomyopathy in certain patients. It is still not known whether persistence of the viral genome contributes to the pathogenesis of dilated cardiomyopathy. Methods and Results-To determine whether low-level enteroviral gene expression similar to that observed with viral persistence can induce myocytopathic effects without formation of infectious virus progeny, the full-length infectious cDNA copy of CVB3 was mutated at the VP0 maturation cleavage site. This prevented formation of infectious virus progeny. In myocytes transfected with this mutated cDNA copy of the viral genome, both positive-and negative-strand viral RNAs were detected, demonstrating that there was replication of the viral genome by the RNA-dependent RNA polymerase. The level of viral protein expression was found to be below limits of detection by conventional methods of protein detection, thus resembling restricted virus replication. Nonetheless, the CVB3 mutant was found to induce a cytopathic effect in transfected myocytes, which was demonstrated by inhibition of cotransfected MLC-2v luciferase reporter activity and an increase in release of lactate dehydrogenase from transfected cells. Conclusions-This study demonstrates that restricted replication of enteroviral genomes in myocytes in a pattern similar to that observed in hearts with persistent viral infection can induce myocytopathic effects without generation of infectious virus progeny. (Circulation. 1998;98:450-457.)

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Section: Discussionmentioning

confidence: 99%

Low-Level Expression of a Mutant Coxsackieviral cDNA Induces a Myocytopathic Effect in Culture

et al. 1998

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“…Studies by Clark and colleagues (Clark & Dasgupta, 1990;Clark et al, 1991Clark et al, , 1993 neural network method suggest that human TFIIIC (TFC3-HUM) may be cleaved between Q732-G (see Table 4), with a cleavage score of 0.644. This prediction supports the results presented in a recent report (Shen et al, 1996).…”

Section: G859mentioning

confidence: 99%

Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

et al. 1996

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Picornaviral proteinases are responsible for maturation cleavages of the viral polyprotein, but also catalyze the degradation of cellular targets. Using graphical visualization techniques and neural network algorithms, we have investigated the sequence specificity of the two proteinases 2AP" and 3CPm. The cleavage of VPO (giving rise to VP2 and VP4). which is carried out by a so-far unknown proteinase, was also examined. In combination with a novel surface exposure prediction algorithm, our neural network approach successfully distinguishes known cleavage sites from noncleavage sites and yields a more consistent definition of features common to these sites. The method is able to predict experimentally determined cleavage sites in cellular proteins. We present a list of mammalian and other proteins that are predicted to be possible targets for the viral proteinases. Whether these proteins are indeed cleaved awaits experimental verification. Additionally, we report several errors detected in the protein databases.A computer server for prediction of cleavage sites by picornaviral proteinases is publicly available at the e-mail address NetPicoRNA@cbs.dtu.dk or via WWW at http://www.cbs.dtu.dkfservices/NetPicoRNA.Keywords: cleavage site prediction; neural networks; picornavirus; proteinase; surface exposureMembers of the picornavirus family express their genomic RNA as a single polyprotein that is proteolytically processed to the mature polypeptides. At least three proteinases are required for the individual protein components to be released (reviewed in Krausslich Hellen et al., 1989;Lawson & Semler, 1990). The primary cleavage, which severs the capsid precursor PI from the nonstructural region P2-P3, is performed cotranslationally by the viral proteinase 2APm in enteroviruses and human rhinoviruses (HRVs; see Fig. I). Most of the remaining cleavages are catalyzed by the viral proteinase, 3CP". In cardio-, hepato-, and aphthoviruses, which also belong to the picornavirus family, the L-proteinase performs functions similar to those of 2APm, resulting in a somewhat different cleavage scheme (see Fig. I). Concomitantly with RNA encapsidation, VPO is cleaved to VP4 and VP2; it is believed that the RNA itself exerts a catalytic function in this event (Arnold et a!., 1987;Harber et al., 1991;Bishop &Anderson, 1993;Basavappa et al., 1994).In addition to processing of the viral polyprotein, the proteinases also cleave cellular targets. When infected with poliovirus, at least nine acidic and five basic cellular proteins were shown to be degraded in two-dimensional gel electrophoresis (Urzanqui & Carrasco, 1989). The degradation of cellular proteins seems to be part of the viral attack mechanism, leading to host cell shur-ofJ-a decrease in cellular transcription and translation that has no influence on viral replication. The best-studied event is the cleavage of the eukaryotic initiation factor 4G (eIF-4G). which is required for cap-dependent translation of cellular mRNA. This protein is degraded by 2APm in entero-and...

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“…In addition to reducing translation of cellular mRNAs, cleavage of host factors by 2A pro and 3C pro is also responsible for disrupting a number of cellular processes. For example, cleavage of nuclear pore complex proteins by 2A pro is thought to be responsible for inhibition of nucleo-cytoplasmic transport (2,38), while cleavage of TFIIIC and TBP by 3C pro contributes to the inhibition of transcription that occurs in infected cells (7,8,51). Numerous other targets for these proteases have been identified, including PABP (21), poly(rC) binding proteins 1 and 2 (41), the La autoantigen (46), the p65 subunit of NF-B (35), and polypyrimidine tract binding protein (1).…”

mentioning

confidence: 99%

Stable Formation of Compositionally Unique Stress Granules in Virus-Infected Cells

Piotrowska

Hansen

Park

et al. 2010

J Virol

107

141

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Stress granules are sites of mRNA storage formed in response to a variety of stresses, including viral infections. Here, the mechanisms and consequences of stress granule formation during poliovirus infection were examined. The results indicate that stress granules containing T-cell-restricted intracellular antigen 1 (TIA-1) and mRNA are stably constituted in infected cells despite lacking intact RasGAP SH3-domain binding protein 1 (G3BP) and eukaryotic initiation factor 4G. Fluorescent in situ hybridization revealed that stress granules in infected cells do not contain significant amounts of viral positive-strand RNA. Infection does not prevent stress granule formation in response to heat shock, indicating that poliovirus does not block de novo stress granule formation. A mutant TIA-1 protein that prevents stress granule formation during oxidative stress also prevents formation in infected cells. However, stress granule formation during infection is more dependent upon ongoing transcription than is formation during oxidative stress or heat shock. Furthermore, Sam68 is recruited to stress granules in infected cells but not to stress granules formed in response to oxidative stress or heat shock. These results demonstrate that stress granule formation in poliovirus-infected cells utilizes a transcription-dependent pathway that results in the appearance of stable, compositionally unique stress granules.

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Direct cleavage of human TATA-binding protein by poliovirus protease 3C in vivo and in vitro.

Cited by 171 publications

References 34 publications

Low-Level Expression of a Mutant Coxsackieviral cDNA Induces a Myocytopathic Effect in Culture

Low-Level Expression of a Mutant Coxsackieviral cDNA Induces a Myocytopathic Effect in Culture

Cleavage site analysis in picornaviral polyproteins: Discovering cellular targets by neural networks

Stable Formation of Compositionally Unique Stress Granules in Virus-Infected Cells

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