Poliovirus Protease 3Cpro Kills Cells by Apoptosis

Barco, Ángel; Feduchi, Elena; Carrasco, Luís

doi:10.1006/viro.1999.0043

Cited by 121 publications

(97 citation statements)

References 63 publications

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“…These apoptotic responses are most likely triggered by the action of the viral proteinases 3C pro and 2A pro , which inhibit cellular transcription and cap-dependent translation, respectively (8,9). Enteroviruses interrupt this apoptotic program by encoding functions that implement an antiapoptotic program (4).…”

Section: Discussionmentioning

confidence: 99%

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The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis

Campanella

Jong²,

Lanke³

et al. 2004

Journal of Biological Chemistry

118

119

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. In our studies of the physiological importance of the 2B-induced alterations in Ca 2؉ signaling, we found that the expression of 2B suppressed caspase activation and apoptotic cell death induced by various stimuli, including actinomycin D and cycloheximide. Mutants of 2B that were defective in reducing the Ca 2؉ content of the stores failed to suppress apoptosis. These data implicate a functional role of the perturbation of intracellular Ca 2؉ compartmentalization in the enteroviral strategy to suppress intrinsic apoptotic host cell responses. The putative down-regulation of an endoplasmic reticulum-dependent apoptotic pathway is discussed.

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Section: Discussionmentioning

confidence: 99%

“…Individual expression of the viral proteinase 2A pro , which inhibits cap-dependent translation of cellular mRNAs, or the expression of 3C pro , which shuts off host cell RNA transcription, results in apoptotic cell death (8,9). Little is known about the identity of the apoptosis-suppressing factors.…”

mentioning

confidence: 99%

The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis

Campanella

Jong²,

Lanke³

et al. 2004

Journal of Biological Chemistry

118

119

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“…Other RNA viruses encode more than one protein that induce apoptosis. Proteases 2A and 3C of poliovirus, envelope glycoproteins E1 and E2 of Sindbis virus, and four proteins of human immunodeficiency virus, gp120, gp41, Tat, and Vpr, induce apoptosis (1,8,9,14,16,22,39). While it is uncertain why viruses have more than one protein that induce apoptosis, different proteins may provide selective advantage for a virus in different environments.…”

Section: Discussionmentioning

confidence: 99%

Langat Flavivirus Protease NS3 Binds Caspase-8 and Induces Apoptosis

Prikhod'ko¹,

Prikhod’ko

Pletnev³

et al. 2002

J Virol

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The flavivirus NS3 protein plays an important role in the cleavage and processing of the viral polyprotein and in the synthesis of the viral RNA. NS3 recruits NS2B and NS5 proteins to form complexes possessing protease and replicase activities through protease and nucleoside triphosphatase/helicase domains. We have found that NS3 also induces apoptosis. Expression of the Langat (LGT) virus NS3 protein resulted in a cleavage of cellular DNA and reduced the viability of cells. Coexpression of NS3 with apoptotic inhibitors (CrmA and P35) and addition of caspase peptide substrates (Z-VAD-FMK and Z-IETD-FMK) to NS3-transfected cells blocked NS3-induced apoptosis. In cotransfection experiments, NS3 bound to caspase-8 and enhanced caspase-8-mediated apoptosis. NS3 and caspase-8 colocalized in the cytoplasm of transfected cells. Deletion analysis demonstrated that at least two regions of NS3 contribute to its apoptotic activities. The protease and helicase domains are each able to bind to caspase-8, while the protease domain alone induces apoptosis. The protease domain and tetrahelix region of the helicase domain are required for NS3 to augment caspase-8-mediated apoptosis. Thus, the LGT virus NS3 protein is a multifunctional protein that binds to caspase-8 and induces apoptosis.The Flavivirus genus includes mostly arthropod-borne pathogens, many of which are widely distributed throughout the world and cause human diseases that vary in severity. The four serotypes of dengue (DEN) virus, Japanese encephalitis (JE) virus, and yellow fever (YF) virus cause millions of cases of disease annually in the tropics and subtropics. Tick-borne encephalitis (TBE) flaviviruses grouped within the TBE complex (Russian spring-summer encephalitis or TBE, Kyasanur forest disease, Langat [LGT], Louping ill, Negishi, Omsk hemorrhagic fever, and Powassan viruses) are mainly found in the Northern Hemisphere and, except for LGT virus, cause thousands of human cases every year, which can have a mortality as high as 20 to 30%.LGT virus does not naturally infect humans and has been studied as a potential live virus vaccine to protect against encephalitis caused by viruses of the TBE complex (4).LGT virus, like other flaviviruses, is a small lipid-enveloped, positive-sense RNA virus. During infection, a single polycistronic viral RNA is translated into a polyprotein precursor that is co-and posttranslationally processed by host and viral proteases to produce the virion and replicase components. The structural proteins of flaviviruses, capsid (C), premembrane (preM), and envelope (E), are encoded in the 5Ј quarter of the genome, and signal peptidase appears to mediate their cleavages during elongation of the polyprotein precursor through the translocating channel of the rough endoplasmic reticulum. Nonstructural proteins NS2A and -B, NS3, NS4A and -B, and NS5 are cleaved by viral serine protease NS2B-NS3 after a sequence that usually contains two basic residues followed by a short side chain residue (reviewed in reference 19).NS3 protein exhibits p...

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“…These infected cells are degrading into apoptotic debris containing virus dsRNA when RIG-I/MDA5 is ineffective at inducing IFN (48). Phagocytic internalization of this infected debris containing viral dsRNA into endosomes in Mf/DC is a critical event for TLR3 stimulation (37).…”

Section: Discussionmentioning

confidence: 99%

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

Oshiumi

Okamoto

Fujii

et al. 2011

The Journal of Immunology

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Cytoplasmic and endosomal RNA sensors recognize RNA virus infection and signals to protect host cells by inducing type I IFN. The cytoplasmic RNA sensors, retinoic acid inducible gene I/melanoma differentiation-associated gene 5, actually play pivotal roles in sensing virus replication. IFN-β promoter stimulator-1 (IPS-1) is their common adaptor for IFN-inducing signaling. Toll/IL-1R homology domain-containing adaptor molecule 1 (TICAM-1), also known as TRIF, is the adaptor for TLR3 that recognizes viral dsRNA in the early endosome in dendritic cells and macrophages. Poliovirus (PV) belongs to the Picornaviridae, and melanoma differentiation-associated gene 5 reportedly detects replication of picornaviruses, leading to the induction of type I IFN. In this study, we present evidence that the TLR3/TICAM-1 pathway governs IFN induction and host protection against PV infection. Using human PVR transgenic (PVRtg) mice, as well as IPS-1−/− and TICAM-1−/− mice, we found that TICAM-1 is essential for antiviral responses that suppress PV infection. TICAM-1−/− mice in the PVRtg background became markedly susceptible to PV, and their survival rates were decreased compared with wild-type or IPS-1−/− mice. Similarly, serum and organ IFN levels were markedly reduced in TICAM-1−/−/PVRtg mice, particularly in the spleen and spinal cord. The sources of type I IFN were CD8α+/CD11c+ splenic dendritic cells and macrophages, where the TICAM-1 pathway was more crucial for PV-derived IFN induction than was the IPS-1 pathway in ex vivo and in vitro analyses. These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection.

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Poliovirus Protease 3Cpro Kills Cells by Apoptosis

Cited by 121 publications

References 63 publications

The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis

The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis

Langat Flavivirus Protease NS3 Binds Caspase-8 and Induces Apoptosis

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

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