MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus

Wang, Jennifer; Cerny, Anna M.; Asher, Damon R.; Kurt-Jones, Evelyn A.; Bronson, Roderick T.; Finberg, Robert W.

doi:10.1128/jvi.00631-09

Cited by 132 publications

(136 citation statements)

References 34 publications

(37 reference statements)

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“…These results, therefore, suggest that an MDA5-mediated signal is the primary activator for type I IFN production in mice following infection with TMEV. A recent study showed that MDA5 KO mice infected with coxsackie B virus, another picornavirus, display impaired type I IFN production and early mortality (45). The reduced type I IFN production is consistent with our results with TMEV infection.…”

Section: Discussionsupporting

confidence: 82%

Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease

Jin

Kim

et al. 2012

J Virol

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Section: Discussionsupporting

confidence: 82%

Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease

Jin

Kim

et al. 2012

J Virol

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“…From these experiments, we conclude that, unlike the profound effect of the MAVS knockout, neither MDA-5 nor RIG-I is essential for the early innate antiviral transcriptional response or IFN-␤ secretion following rotavirus infection. ther RIG-I nor MDA-5 is essential for mounting an effective IFN response to rotavirus infection, these RLRs could act cooperatively or redundantly to induce a response to rotavirus, a phenomenon observed during infection with other viruses (19,35,58). In order to address this possibility, we used an RNA interference approach to inhibit expression of one RLR in the reciprocal knockout cell.…”

Section: Rotaviruses Induce Early Antiviral Transcriptional Responsesmentioning

confidence: 99%

The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3

Pruijssers

Dermody

et al. 2011

J Virol

134

136

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In mouse embryonic fibroblasts (MEFs), the bovine rotavirus (UK strain) but not the simian rhesus rotavirus (RRV) robustly triggers beta interferon (IFN-␤Rotaviruses are etiological agents of severe dehydrating diarrhea in infants and young children and cause nearly 600,000 deaths globally every year (34). Rotaviruses are nonenveloped icosahedral members of the family Reoviridae and contain 11 segments of genomic double-stranded RNA (dsRNA) within a triple-layered particle. Several rotavirus vaccines have been developed to reduce rotavirus-associated mortalities (26); some are based on a modified Jennerian principle of rotavirus attenuation in the heterologous host. This phenomenon is termed host range restriction and is manifested by poor replication of rotaviruses in heterologous hosts compared to that in the homologous host (1). For example, bovine, lapine, and simian rotaviruses are all restricted for replication in humans. We are interested in understanding the mechanisms underlying host range restriction of rotaviruses in order to improve our basic knowledge of viral pathogenesis and because of the importance of these mechanisms in rational attenuation of vaccine candidates.In primary mouse embryonic fibroblasts (MEFs), several heterologous (nonmurine) rotavirus strains, including the bovine UK strain, are replication restricted by the host type I interferon (IFN) response (17, 53). In contrast, replication of homologous murine EW virus and the heterologous simian rhesus rotavirus (RRV) strain is insensitive to the presence of the interferon system. In a mouse model of rotavirus infection, RRV replication in gallbladder epithelia correlates with its ability to suppress the IFN response (N. Feng et al., submitted for publication). The rotavirus gene segment encoding the nonstructural protein 1 (NSP1) is an important determinant of host restriction of viral replication both in vitro (17,53) and in vivo (9). Specifically, we along with others have reported a role for NSP1 in regulating the ability of rotavirus to efficiently cause diarrhea in mice (9), spread from animal to animal (9), replicate in vivo and in vitro (4,(15)(16)(17), and antagonize IFN (4,5,17,24,25,53). Thus, the host innate immune response is an important determinant of rotavirus host range restriction and depends on both the virus strain and host cell or tissue type.Mammalian innate immunity to viral infection is critically dependent on a successful type I IFN response (49). The early IFN response involves initial recognition of virus within infected cells by activation of host pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs)

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“…Although members of the family have been shown to trigger the innate immune response via TLRs (Triantafilou and Triantafilou, 2004;Richer et al, 2006;Triantafilou et al, 2005) and by MDA5 Loo et al, 2008;Wang et al, 2010), little is known about the exact ligand. Total RNA extracted from enteroviruses triggers MDA5, however the specific ligand within such pools has not been identified.…”

Section: Introductionmentioning

confidence: 99%

“…RIG-I recognises negative sense ssRNA viruses including influenza virus, Newcastle disease virus, Sendai virus as well as hepatitis C virus, while positive sense ssRNA viruses such as picornaviruses, and more specifically encephalomyocarditis virus and coxcackievirus B3 have been shown to activate MDA5 and trigger IFN response Loo et al, 2008;Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Visualisation of direct interaction of MDA5 and the dsRNA replicative intermediate form of positive strand RNA viruses

Triantafilou

Vakakis

Kar

et al. 2012

Journal of Cell Science

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SummaryThe innate immune system is a vital part of the body's defences against viral pathogens. The proteins retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) function as cytoplasmic pattern recognition receptors that are involved in the elimination of actively replicating RNA viruses. Their location and their differential responses to RNA viruses emphasises the complexity of the innate detection system. Despite the wealth of information on the types of RNA that trigger RIG-I, much less is known about the nature of the RNAs that act as agonists for MDA5. In order to identify which RNA species triggers MDA5 activation during infection, we isolated viral ssRNA and replicative intermediates of RNA from positive sense ssRNA viruses. We reveal that MDA5 recognises not the genomic ssRNA but the dsRNA generated by the replication of these viruses. Furthermore, using fluorescent imaging we present the first report of the visualisation of dsRNA and MDA5, which provides unique evidence of the relationship between viral dsRNA and MDA5 and proves without a doubt that MDA5 is the key sensor for the dsRNA replicative intermediate form of positive sense ssRNA viruses.

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MDA5 and MAVS Mediate Type I Interferon Responses to Coxsackie B Virus

Cited by 132 publications

References 34 publications

Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease

Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease

The Early Interferon Response to Rotavirus Is Regulated by PKR and Depends on MAVS/IPS-1, RIG-I, MDA-5, and IRF3

Visualisation of direct interaction of MDA5 and the dsRNA replicative intermediate form of positive strand RNA viruses

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