The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment

Daughenbaugh, Katie F.; Fraser, Chris S.; Hershey, John W.B.; Hardy, Michele E.

doi:10.1093/emboj/cdg251

Cited by 180 publications

(166 citation statements)

References 45 publications

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“…Murine Norovirus RNA Translation Is Insensitive to Cap Analogue-To date, the study of norovirus translation has been limited to in vitro binding analysis of the recombinant norovirus VPg with translation initiation factors (18). To fully evaluate the functional roles of initiation factors in norovirus translation, an in vitro translation system was required.…”

Section: Resultsmentioning

confidence: 99%

“…4). Given that a direct interaction of norovirus VPg with eIF3 has been previously reported (18), one might then predict that eIF3 (and hence the C-terminal fragment of eIF4G, which contains the eIF4A-binding sites) would still be recruited even when eIF4G is cleaved. Unlike our previous observations with FCV, where eIF4G cleavage occurs at late stages of virus replication (37), eIF4G cleavage was not apparent during MNV infection (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…4 porcine enteric calicivirus, and MNV have been used as model systems to study calicivirus biology. We and others have previously reported that caliciviruses use a novel protein-directed translation initiation mechanism that involves the binding of translation initiation factors to the VPg protein that is covalently linked to the 5Ј end of the viral RNA (18,19). This mechanism has not been demonstrated in any other animal RNA virus but shares some similarity with a mechanism proposed for members of the plant potyvirus family (20 -23).…”

mentioning

confidence: 80%

“…Recent work has highlighted a novel translation initiation mechanism used by members of the Caliciviridae and Potyviridae families (18,19,23). This mechanism relies on the interaction of translation initiation factors with a protein (VPg) covalently linked to the 5Ј end of the viral genome.…”

Section: Discussionmentioning

confidence: 99%

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Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Chaudhry

Nayak

Bordeleau

et al. 2006

Journal of Biological Chemistry

131

199

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Two classes of viruses, namely members of the Potyviridae and Caliciviridae, use a novel mechanism for the initiation of protein synthesis that involves the interaction of translation initiation factors with a viral protein covalently linked to the viral RNA, known as VPg. The calicivirus VPg proteins can interact directly with the initiation factors eIF4E and eIF3. Translation initiation on feline calicivirus (FCV) RNA requires eIF4E because it is inhibited by recombinant 4E-BP1. However, to date, there have been no functional studies carried out with respect to norovirus translation initiation, because of a lack of a suitable source of VPg-linked viral RNA. We have now used the recently identified murine norovirus (MNV) as a model system for norovirus translation and have extended our previous studies with FCV RNA to examine the role of the other eIF4F components in translation initiation. We now demonstrate that, as with FCV, MNV VPg interacts directly with eIF4E, although, unlike FCV RNA, translation of MNV RNA is not sensitive to 4E-BP1, eIF4E depletion, or foot-and-mouth disease virus Lb protease-mediated cleavage of eIF4G. We also demonstrate that both FCV and MNV RNA translation require the RNA helicase component of the eIF4F complex, namely eIF4A, because translation was sensitive (albeit to different degrees) to a dominant negative form and to a small molecule inhibitor of eIF4A (hippuristanol). These results suggest that calicivirus RNAs differ with respect to their requirements for the components of the eIF4F translation initiation complex.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Chaudhry

Nayak

Bordeleau

et al. 2006

Journal of Biological Chemistry

131

199

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“…In feline calicivirus, viral genome RNA without VPg is not infectious (34). Recent data indicate that VPg may function in the initiation of translation of NV RNA (35); however, the exact functions of VPg in NV replication still remain unclear. VPg proteins derived from positive-strand viruses in families other than Caliciviridae have multiple functions in viral RNA replication, translation, and encapsidation (36).…”

Section: Discussionmentioning

confidence: 99%

Replication and packaging of Norwalk virus RNA in cultured mammalian cells

Asanaka

Atmar

Ruvolo

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

102

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Human noroviruses, the most common cause of nonbacterial gastroenteritis, are characterized by high infectivity rate, low infectious dose, and unusually high stability outside the host. However, human norovirus research is hindered by the lack of a cell culture system and a small animal model of infection. Norwalk virus (NV) is the prototype strain of human noroviruses. We report here replication of NV viral RNA and its packaging into virus particles in mammalian cells by intracellular expression of native forms of NV viral RNA devoid of extraneous nucleotide sequences derived from the expression vector by the use of replication-deficient vaccinia virus MVA encoding the bacteriophage T7 RNA polymerase (MVA͞ T7). Expressed genomic RNA was found to replicate; NV subgenomic RNA was transcribed from genomic RNA by use of NV nonstructural proteins expressed from genomic RNA and was subsequently translated into NV capsid protein VP1. Viral genomic RNA was packaged into virus particles generated in mammalian cells. The cesium chloride (CsCl) density gradient profile of virus particles containing genomic RNA was similar to that of NV purified from stool. These observations indicate that the NV cDNA constructed here is a biologically infectious clone, and that mammalian cells have the ability to replicate NV genomic RNA. This work establishes a mammalian cell-based system for analysis of human norovirus replication and, thus, makes it feasible to investigate antiviral agents in mammalian cells.human norovirus ͉ norovirus RNA replication N oncultivatable human norovirus belongs to the Norovirus genus of the family Caliciviridae and is classified as a Group B biodefense pathogen. Human noroviruses are responsible for almost all outbreaks (Ͼ95%) of nonbacterial gastroenteritis in the United States and Europe (1, 2). Incidents of the rapid spread of norovirus-related illness in the cruise ship industry have led to an increased recognition of the impact of norovirus infections on public health (3).Norwalk virus (NV), the prototype strain of human norovirus, is a nonenveloped virus that contains a Ϸ7.7-kb positive-sense single-stranded RNA genome (4). The NV genome is polyadenylated at its 3Ј end and encodes three primary ORFs (Fig. 1A) (4). ORF1 encodes a nonstructural polyprotein containing the following genes from the 5Ј end to the 3Ј end, respectively: p48, nucleotide triphosphatase (NTPase), p22, VPg, protease (Pro), and RNA polymerase (RNA Pol) (Fig. 1 A) (5). ORF2 and ORF3 encode structural proteins, the major capsid protein (VP1) and a minor structural protein (VP2), respectively ( Fig. 1 A) (4). Expression of VP1 in insect cells infected with baculovirus recombinants results in the self-assembly of empty recombinant virus-like particles (VLPs) (6, 7). VP2 is also incorporated into VLPs when VP2 is coexpressed with VP1 (8), and its presence increases the yield and stability of VLPs (9).Since the initial cloning and sequencing of the NV genome (4, 10), many other norovirus sequences have been reported (11,12). Despite ...

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Noroviruses

Bailey¹,

Goodfellow²

2009

Encyclopedia of Life Sciences

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Noroviruses are one of the primary causes of acute gastroenteritis in man in the developed world, yet may also cause acute and persistent infections in animals. The study of noroviruses has been largely hindered by the lack of an efficient cell culture system for the viruses which infect humans. However, new advances in molecular techniques and the identification of animal noroviruses have led to a recent increase in our understanding of the structure and function of the virus, as well as the proteins encoded by the positive‐stranded ribonucleic acid (RNA) genome. Our knowledge of the molecular mechanism of norovirus genome translation and replication lags behind that of many positive‐stranded RNA viruses but recent studies have highlighted some unique and interesting features of these economically important pathogens. Key Concepts: The causative agent of norovirus disease is a small RNA virus. The virus replicates in the gastrointestinal tract of its host. Noroviruses infect a wide range of mammals, including humans where they represent a significant cause of viral gastroenteritis. Noroviruses are highly transmissible and capable of causing serious epidemics. Norovirus virions have icosahedral symmetry. The norovirus genome is positive sense, meaning it is directly translated into proteins. Norovirus genome replication is thought to occur through an antigenome intermediate. The replication process takes place in the cytoplasm of infected cells. Reverse genetics systems are available for some noroviruses allowing detailed investigation of their replication strategies and the molecular determinants of their pathogenicity.

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The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment

Cited by 180 publications

References 45 publications

Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Replication and packaging of Norwalk virus RNA in cultured mammalian cells

Noroviruses

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