MDA-5 Is Cleaved in Poliovirus-Infected Cells

Barral, Paola M.; Morrison, Juliet; Drahos, Jennifer; Gupta, Pankaj; Sarkar, Devanand; Fisher, Paul B.; Racaniello, Vincent R.

doi:10.1128/jvi.01360-06

Cited by 176 publications

(195 citation statements)

References 37 publications

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“…We have already mentioned the induction of caspase-mediated cleavage of IRF3 by infection with Sendai virus and adenovirus (28). In addition, poliovirus infection promotes caspase-mediated cleavage of the cytoplasmic RNA helicase MDA-5, which senses the viral doublestranded RNA in the context of the innate anti-viral response (40). Like these viruses, HIV-1 may have been evolved to utilize caspase activation to interfere with IRF3 function.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor

Park

Waheed

Zhang

et al. 2014

Journal of Biological Chemistry

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Background:The transcription factor IRF3 is not properly activated during HIV-1 infection. Results: Infection with VSV-G-pseudotyped HIV-1 induces caspase-mediated cleavage of IRF3, and Vpu contributes to this event. Conclusion:The product of IRF3 cleavage by HIV-1 interferes with IRF3-regulated gene expression. Significance: Our findings contribute to the understanding of how HIV-1 attenuates the innate anti-viral response.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor

Park

Waheed

Zhang

et al. 2014

Journal of Biological Chemistry

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“…Some enteroviruses including poliovirus have been shown previously to induce proteasome-and/or caspase-dependent degradation of MDA5 (Barral et al, 2007;Drahos & Racaniello, 2009;Rebsamen et al, 2008).…”

Section: Cvb3 Infection Negatively Affects the Protein Expression Levmentioning

confidence: 99%

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

Lind

Svedin

Domsgen

et al. 2016

Journal of General Virology

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Type I IFNs play an important role in the immune response to enterovirus infections. Their importance is underscored by observations showing that many enteroviruses including coxsackie B viruses (CVBs) have developed strategies to block type I IFN production. Recent studies have highlighted a role for the type III IFNs (also called IFNls) in reducing permissiveness to infections with enteric viruses including coxsackievirus. However, whether or not CVBs have measures to evade the effects of type III IFNs remains unknown. By combining virus infection studies and different modes of administrating the dsRNA mimic poly I : C, we discovered that CVBs target both Toll-like receptor 3-and MDA5/RIG-I-mediated type III IFN expression. Consistent with this, the cellular protein expression levels of the signal transduction proteins TRIF and IPS1 were reduced and no hyperphosphorylation of interferon regulatory factor 3 was observed following infection with the virus. Notably, decreased expression of full-length TRIF and IPS1 and the appearance of cleavage products was observed upon both CVB3 infection and in cellular protein extracts incubated with recombinant 2A pro , indicating an important role for the viral protease in subverting the cellular immune system. Collectively, our study reveals that CVBs block the expression of type III IFNs, and that this is achieved by a similar mechanism as the virus uses to block type I IFN production. We also demonstrate that the virus blocks several intracellular viral recognition pathways of importance for both type I and III IFN production. The simultaneous targeting of numerous arms of the host immune response may be required for successful viral replication and dissemination.

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“…Cleavage of the polyprotein normally occurs between glutamine-glycine or glutamine-serine amino acid pairs, which are usually flanked by proline residues (Palmenberg et al, 1984). Besides its commitment to the processing of the viral polyprotein, picornaviral 3C PRO can also facilitate virus replication by altering fundamental cellular processes such as transcription and translation of host cell mRNA (Barral et al, 2007;Ehrenfeld, 1982;Kuyumcu-Martinez et al, 2004; Neznanov et al, 2005;Shen et al, 1996;Yalamanchili et al, 1996Yalamanchili et al, , 1997. Because the regulated proteolysis mediated by 3C PRO is a critical feature in both the processing of picornaviral polyprotein and the inhibition of cellular defences, 3C PRO constitutes an important target for host antiviral innate pathways.…”

mentioning

confidence: 99%

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

Eldin

Papon

Oteiza

et al. 2009

Journal of General Virology

110

108

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The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-induced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C PRO ) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses. INTRODUCTIONPicornaviruses include important human pathogens such as rhinovirus, poliovirus and hepatitis A virus, as well as significant insect, plant and agricultural pathogens, such as foot-and-mouth disease virus (Whitton et al., 2005). Encephalomyocarditis virus (EMCV) is the prototype of the cardiovirus subgroup of picornaviruses. Its genome consists of a single-strand of messenger-sense RNA. Viral proteins are expressed from a large open reading frame encoding a giant precursor polyprotein (approx. 255 kDa), which is processed through a series of proteolytic cleavages to produce both capsid and non-structural proteins (Palmenberg, 1990). The majority of the processing reactions are carried out by the 3C protease (3C PRO ), which acts both inter-and intramolecularly to produce polyprotein precursors as well as the mature 3C PRO polypeptide (Palmenberg et al., 1979). Cleavage of the polyprotein normally occurs between glutamine-glycine or glutamine-serine amino acid pairs, which are usually flanked by proline residues (Palmenberg et al., 1984). Besides its commitment to the processing of the viral polyprotein, picornaviral 3C PRO can also facilitate virus replication by altering fundamental cellular processes such as transcription and translation of host cell mRNA (Barral et al., 2007;Ehrenfeld, 1982;Kuyumcu-Martinez et al., 2004; Neznanov et al., 2005;Shen et al., 1996;Yalamanchili et al., 1996Yalamanchili et al., , 1997. Because the regulated proteolysis mediated by 3C PRO is a critical feature in both the processing of picornaviral polyprotein and the inhibition of cellular defences, 3C PRO constitutes an important target for host antiviral innate pathways. Consistent with this, the degradation of EMCV 3C PRO by the ubiquitin/26S proteasome system has been reported (Losick et al., 2003;Schlax et al., 2007). Although the precise ro...

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MDA-5 Is Cleaved in Poliovirus-Infected Cells

Cited by 176 publications

References 37 publications

HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor

HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

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