Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus

Katze, Michael G.; DeCorato, Douglas R.; Krug, Robert M.

doi:10.1128/jvi.60.3.1027-1039.1986

Cited by 82 publications

(39 citation statements)

References 65 publications

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“…Influenza virus efficiently shuts off host cell protein synthesis (21). Upon infection of susceptible cells, initiation and elongation steps of translation of cellular mRNAs are inhibited (31). This translational control is accompanied by a selective translation of viral mRNAs, with the sequences within the 5Ј untranslated regions (UTRs) playing a critical role (21).…”

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confidence: 99%

“…This translational control is accompanied by a selective translation of viral mRNAs, with the sequences within the 5Ј untranslated regions (UTRs) playing a critical role (21). The NS1 viral protein is important for the selective translation of viral messengers, especially for the late ones, by increasing their rate of initiation (10,14,31,43). This process is mediated by its functional interaction with the 5Ј-terminal conserved sequences of viral mRNAs (10,43).…”

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confidence: 99%

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Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?

Burgui

Yángüez

Sonenberg

et al. 2007

J Virol

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Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5 ends derived from the host cell pre-mRNAs by a "cap-snatching" mechanism, followed immediately by a common viral sequence. At their 3 ends, they contain a poly(A) tail. Although cellular and viral mRNAs are structurally similar, influenza virus promotes the selective translation of its mRNAs despite the inhibition of host cell protein synthesis. The viral polymerase performs the cap snatching and binds selectively to the 5 common viral sequence. As viral mRNAs are recognized by their own cap-binding complex, we tested whether viral mRNA translation occurs without the contribution of the eIF4E protein, the cellular factor required for cap-dependent translation. Here, we show that influenza virus infection proceeds normally in different situations of functional impairment of the eIF4E factor. In addition, influenza virus polymerase binds to translation preinitiation complexes, and furthermore, under conditions of decreased eIF4GI association to cap structures, an increase in eIF4GI binding to these structures was found upon influenza virus infection. This is the first report providing evidence that influenza virus mRNA translation proceeds independently of a fully active translation initiation factor (eIF4E). The data reported are in agreement with a role of viral polymerase as a substitute for the eIF4E factor for viral mRNA translation.

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confidence: 99%

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confidence: 99%

Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?

Burgui

Yángüez

Sonenberg

et al. 2007

J Virol

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“…Therefore, viral mRNAs are formally equivalent to cellular mRNAs (31,33). Nevertheless, influenza virus inhibits cellular mRNA translation at both initiation and elongation steps (27), while it selectively enhances viral mRNA translation, with the sequences contained within the 5Ј untranslated region (5Ј UTR) playing a critical role (14).…”

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confidence: 99%

Eukaryotic Translation Initiation Factor 4GI Is a Cellular Target for NS1 Protein, a Translational Activator of Influenza Virus

et al. 2000

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Influenza virus NS1 protein is an RNA-binding protein whose expression alters several posttranscriptional regulatory processes, like polyadenylation, splicing, and nucleocytoplasmic transport of cellular mRNAs. In addition, NS1 protein enhances the translational rate of viral, but not cellular, mRNAs. To characterize this effect, we looked for targets of NS1 influenza virus protein among cellular translation factors. We found that NS1 coimmunoprecipitates with eukaryotic initiation factor 4GI (eIF4GI), the large subunit of the cap-binding complex eIF4F, either in influenza virus-infected cells or in cells transfected with NS1 cDNA. Affinity chromatography studies using a purified His-NS1 protein-containing matrix showed that the fusion protein pulls down endogenous eIF4GI from COS-1 cells and labeled eIF4GI translated in vitro, but not the eIF4E subunit of the eIF4F factor. Similar in vitro binding experiments with eIF4GI deletion mutants indicated that the NS1-binding domain of eIF4GI is located between residues 157 and 550, in a region where no other component of the translational machinery is known to interact. Moreover, using overlay assays and pull-down experiments, we showed that NS1 and eIF4GI proteins interact directly, in an RNA-independent manner. Mapping of the eIF4GI-binding domain in the NS1 protein indicated that the first 113 N-terminal amino acids of the protein, but not the first 81, are sufficient to bind eIF4GI. The first of these mutants has been previously shown to act as a translational enhancer, while the second is defective in this activity. Collectively, these and previously published data suggest a model where NS1 recruits eIF4GI specifically to the 5 untranslated region (5 UTR) of the viral mRNA, allowing for the preferential translation of the influenza virus messengers.

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“…Such a shutdown of protein synthesis has been reported earlier in the context of infection by many eukaryotic viruses such as adenovirus, influenza virus, etc. (61). Notably, the enteric pathogen P. entomophila was an example of a bacterium that blocks host translation in the gut (62).…”

Section: Discussionmentioning

confidence: 99%

Deregulated AUF1 Assists BMP-EZH2–Mediated Delayed Wound Healing during Candida albicans Infection

Mahadik

Yadav

Bhatt

et al. 2018

The Journal of Immunology

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Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element–binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling. Concomitantly, PI3K/PKCδ mobilized the rapid phosphorylation of BMP-responsive Smad1/5/8. Activated BMP pathway orchestrated the elevated recruitment of EZH2 at promoters of genes assisting timely wound closure. In vivo, the repressive H3K27 trimethylation was observed to persist, accompanied by a robust upregulation of BMP pathway upon infection with C. albicans, culminating in delayed wound healing. Altogether, we uncovered the signaling networks coordinated by fungal colonies that are now increasingly associated with the infected wound microbiome, resulting in altered wound fate.

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Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus

Abstract: During influenza virus infection, protein synthesis is maintained at high levels and a dramatic switch from cellular to viral protein synthesis occurs despite the presence of high levels of functional cellular mRNAs in the cytoplasm of infected cells (M. G.

Cited by 82 publications

References 65 publications

Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?

Influenza Virus mRNA Translation Revisited: Is the eIF4E Cap-Binding Factor Required for Viral mRNA Translation?

Eukaryotic Translation Initiation Factor 4GI Is a Cellular Target for NS1 Protein, a Translational Activator of Influenza Virus

Deregulated AUF1 Assists BMP-EZH2–Mediated Delayed Wound Healing during Candida albicans Infection

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