Chapter 3 Virus Versus Host Cell Translation

Komarova, Anastassia V.; Haenni, Anne‐Lise; Ramirez, Bertha Cécilia

doi:10.1016/s0065-3527(09)73003-9

Cited by 9 publications

(7 citation statements)

References 386 publications

(303 reference statements)

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“…Translation of viral products is the first step in the reproductive cycle of eukaryotic plus-strand RNA viruses once they enter a cell and become uncoated. As viruses do not encode their own ribosomes, such a process entirely relies on the translational machinery of the host [ 1 – 3 ]. In eukaryotes, the cytosolic translation apparatus usually recognizes monocystronic mRNAs with a 5´-cap (m 7 GpppN) and a 3´-poly(A) tail, two structures that function synergistically to facilitate translation [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient Translation of Pelargonium line pattern virus RNAs Relies on a TED-Like 3´-Translational Enhancer that Communicates with the Corresponding 5´-Region through a Long-Distance RNA-RNA Interaction

et al. 2016

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Cap-independent translational enhancers (CITEs) have been identified at the 3´-terminal regions of distinct plant positive-strand RNA viruses belonging to families Tombusviridae and Luteoviridae. On the bases of their structural and/or functional requirements, at least six classes of CITEs have been defined whose distribution does not correlate with taxonomy. The so-called TED class has been relatively under-studied and its functionality only confirmed in the case of Satellite tobacco necrosis virus, a parasitic subviral agent. The 3´-untranslated region of the monopartite genome of Pelargonium line pattern virus (PLPV), the recommended type member of a tentative new genus (Pelarspovirus) in the family Tombusviridae, was predicted to contain a TED-like CITE. Similar CITEs can be anticipated in some other related viruses though none has been experimentally verified. Here, in the first place, we have performed a reassessment of the structure of the putative PLPV-TED through in silico predictions and in vitro SHAPE analysis with the full-length PLPV genome, which has indicated that the presumed TED element is larger than previously proposed. The extended conformation of the TED is strongly supported by the pattern of natural sequence variation, thus providing comparative structural evidence in support of the structural data obtained by in silico and in vitro approaches. Next, we have obtained experimental evidence demonstrating the in vivo activity of the PLPV-TED in the genomic (g) RNA, and also in the subgenomic (sg) RNA that the virus produces to express 3´-proximal genes. Besides other structural features, the results have highlighted the key role of long-distance kissing-loop interactions between the 3´-CITE and 5´-proximal hairpins for gRNA and sgRNA translation. Bioassays of CITE mutants have confirmed the importance of the identified 5´-3´ RNA communication for viral infectivity and, moreover, have underlined the strong evolutionary constraints that may operate on genome stretches with both regulatory and coding functions.

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Section: Introductionmentioning

confidence: 99%

Efficient Translation of Pelargonium line pattern virus RNAs Relies on a TED-Like 3´-Translational Enhancer that Communicates with the Corresponding 5´-Region through a Long-Distance RNA-RNA Interaction

et al. 2016

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“…Viruses rely on the host cell for translation of their mRNAs. A common innate antiviral mechanism is to globally inhibit protein synthesis through the phosphorylation of the alpha subunit of the factor eukaryotic initiation factor 2 (eIF-2a,P) (reviewed in [9,10]). In the absence of eIF-2a,P, a complex consisting of eIF2, GTP, and a methionine-tRNA binds to a 40S ribosomal subunit to form the 43S preinitiation complex.…”

Section: Introductionmentioning

confidence: 99%

“…Multiple RNA viruses have devised strategies to circumvent host cell translation control. A common example would be viral 59-UTRs that possess an internal ribosomal entry site (IRES) which allows translation of viral RNA without a 59-m 7 G cap, thereby permitting translation of proteins in a cell where cap-dependent translation is impaired [9,10,17]. Notably, NNS RNA viruses have not been demonstrated to encode IRESes.…”

Section: Introductionmentioning

confidence: 99%

An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication

et al. 2013

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Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, the 5′-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5′-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a β-actin 5′-UTR. The L 5′-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5′-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a “weak” Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10–100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.

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“…In addition, these viruses often encode proteins that target the host translation factors in order to shut down host translation and/or to boost viral translation . For example, viruses encode proteases that specifically cleave eIFs . Later on, it has been discovered that IRESs also exist in cellular mRNAs that are translated when canonical cap‐dependent translation is inactivated .…”

Section: Introductionmentioning

confidence: 99%

Viral internal ribosomal entry sites: four classes for one goal

2017

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To ensure efficient propagation, viruses need to rapidly produce viral proteins after cell entrance. Since viral genomes do not encode any components of the protein biosynthesis machinery, viral proteins must be produced by the host cell. To hi-jack the host cellular translation, viruses use a great variety of distinct strategies. Many single-stranded positive-sensed RNA viruses contain so-called internal ribosome entry sites (IRESs). IRESs are structural RNA motifs that have evolved to specific folds that recruit the host ribosomes on the viral coding sequences in order to synthesize viral proteins. In host canonical translation, recruitment of the translation machinery components is essentially guided by the 5' cap (m G) of mRNA. In contrast, IRESs are able to promote efficient ribosome assembly internally and in cap-independent manner. IRESs have been categorized into four classes, based on their length, nucleotide sequence, secondary and tertiary structures, as well as their mode of action. Classes I and II require the assistance of cellular auxiliary factors, the eukaryotic intiation factors (eIF), for efficient ribosome assembly. Class III IRESs require only a subset of eIFs whereas Class IV, which are the more compact, can promote translation without any eIFs. Extensive functional and structural investigations of IRESs over the past decades have allowed a better understanding of their mode of action for viral translation. Because viral translation has a pivotal role in the infectious program, IRESs are therefore attractive targets for therapeutic purposes. WIREs RNA 2018, 9:e1458. doi: 10.1002/wrna.1458 This article is categorized under: Translation > Ribosome Structure/Function Translation > Translation Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

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Chapter 3 Virus Versus Host Cell Translation

Cited by 9 publications

References 386 publications

Efficient Translation of Pelargonium line pattern virus RNAs Relies on a TED-Like 3´-Translational Enhancer that Communicates with the Corresponding 5´-Region through a Long-Distance RNA-RNA Interaction

Efficient Translation of Pelargonium line pattern virus RNAs Relies on a TED-Like 3´-Translational Enhancer that Communicates with the Corresponding 5´-Region through a Long-Distance RNA-RNA Interaction

An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication

Viral internal ribosomal entry sites: four classes for one goal

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