Nuclear factors are involved in hepatitis C virus RNA replication

Isken, Olaf; Baroth, Martina; Grassmann, Claus W.; Weinlich, Susan; Ostareck, Dirk H.; Ostareck-Lederer, Antje; Behrens, Sven-Erik

doi:10.1261/rna.594207

Cited by 143 publications

(185 citation statements)

References 57 publications

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“…From these, SLIII is proposed to interact with the 40S ribosomal subunits thus playing a key role in translation initiation. The SLII and SLIII stem loops function in replication as well (13,15). Electromobility shift analysis showed that the SLIII was both necessary and sufficient for binding of the LSm1-7 ring to the 5ЈUTR region (Fig.…”

Section: Depletion Of the Proteins Dcp2 And Xrn1 Does Not Affect Infementioning

confidence: 97%

Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates

Scheller

Mina

Galão

et al. 2009

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

128

166

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Inevitably, viruses depend on host factors for their multiplication. Here, we show that hepatitis C virus (HCV) RNA translation and replication depends on Rck/p54, LSm1, and PatL1, which regulate the fate of cellular mRNAs from translation to degradation in the 5 -3 -deadenylation-dependent mRNA decay pathway. The requirement of these proteins for efficient HCV RNA translation was linked to the 5 and 3 untranslated regions (UTRs) of the viral genome. Furthermore, LSm1-7 complexes specifically interacted with essential cis-acting HCV RNA elements located in the UTRs. These results bridge HCV life cycle requirements and highly conserved host proteins of cellular mRNA decay. The previously described role of these proteins in the replication of 2 other positive-strand RNA viruses, the plant brome mosaic virus and the bacteriophage Qß, pinpoint a weak spot that may be exploited to generate broad-spectrum antiviral drugs.deadenylation-dependent mRNA decay ͉ HCV ͉ host factors ͉ LSm1-7 ͉ Rck/p54

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Section: Depletion Of the Proteins Dcp2 And Xrn1 Does Not Affect Infementioning

confidence: 97%

Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates

Scheller

Mina

Galão

et al. 2009

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

128

166

View full text Add to dashboard Cite

show abstract

“…It suppresses the function of Ebola virus polymerases through interaction with VP35 (14), inhibits HIV replication through interaction with HIV-1 TAR RNA (15,16), represses internal ribosome entry sites in rhinoviruses (17,18) and negatively regulates influenza virus replication through interaction with viral nucleoprotein (NP) (19). However, other studies (20)(21)(22)(23) found that NF90 is required for the replication of some positivestranded RNA viruses and is important for expression of E6 protein in human papillomavirus-infected cells. It is postulated that, although members of the NF90 family generally serve as components of host antiviral responses, some viruses may have adapted a mechanism to hijack NF90, retasking it for viral replication and weakening host defenses (20).…”

mentioning

confidence: 99%

NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells

Wen

Huang

Mok

et al. 2014

The Journal of Immunology

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NF90 was shown to exhibit broad antiviral activity against several viruses, but detailed mechanisms remain unclear. In this study, we examined the molecular basis for the inhibitory effect of NF90 on virus replication mediated through protein kinase (PKR)-associated translational regulation. We first verified the interaction between NF90 and PKR in mammalian cells and showed that NF90 interacts with PKR through its C-terminal and that the interaction is independent of NF90 RNA-binding properties. We further showed that knockdown of NF90 resulted in significantly lower levels of PKR phosphorylation in response to dsRNA induction and influenza virus infection. We also showed that high concentrations of NF90 exhibit negative regulatory effects on PKR phosphorylation, presumably through competition for dsRNA via the C-terminal RNA-binding domain. PKR activation is essential for the formation of stress granules in response to dsRNA induction. Our results showed that NF90 is a component of stress granules. In NF90-knockdown cells, dsRNA treatment induced significantly lower levels of stress granules than in control cells. Further evidence for an NF90–PKR antiviral pathway was obtained using an NS1 mutated influenza A virus specifically attenuated in its ability to inhibit PKR activation. This mutant virus replicated indistinguishably from wild-type virus in NF90-knockdown cells, but not in scrambled control cells or Vero cells, indicating that NF90’s antiviral function occurs through interaction with PKR. Taken together, these results reveal a yet-to-be defined host antiviral mechanism in which NF90 upregulation of PKR phosphorylation restricts virus infection.

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“…31,[68][69][70] In HIV-1, DHX9 is associated with the viral gag protein, and is encapsulated into virions. 71 Viral particles lacking DHX9 are less infectious and show reduced reverse transcriptase activity, implicating DHX9 in reverse transcription.…”

mentioning

confidence: 99%