Degradation of the interferon-induced 68,000-M(r) protein kinase by poliovirus requires RNA

Black, T.; Barber, Glen N.; Katze, Michael G.

doi:10.1128/jvi.67.2.791-800.1993

Cited by 82 publications

(27 citation statements)

References 83 publications

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“…by squelching activator dsRNAs Davies et al, 1993). Poliovirus has been shown to recruit a cellular protease that apparently works in conjunction with poliovirus-specific dsRNA to degrade PKR (Black et al, 1993). Influenza virus also triggers a host cell protein (p58) that is a member of the tetratricopeptide repeat (TPR) family of proteins to down-regulate PKR (Lee et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus

et al. 1998

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Section: Discussionmentioning

confidence: 99%

The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus

et al. 1998

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“…Although many viruses suppress PKR function using various strategies [32], poliovirus is known to promote PKR degradation in infected cells [60,61]; poliovirus RNA and viral protein components are required for this activity [61], and both eIF2a and PKR are highly activated in poliovirus-infected cells before PKR downregulation occurs [60]. In contrast to poliovirus, only RVFV NSs protein was probably required for PKR downregu-lation since the downregulation of PKR occurred as early as 4 h.p.i.…”

Section: Possible Mechanisms Of the Nss-mediated Pkr Downregulationmentioning

confidence: 99%

Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

et al. 2009

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Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

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“…236 The detailed mechanism of this degradation is not fully understood, although it has been suggested that cellular rather than viral proteases are required. 237 Finally, it has been shown recently that the NSs protein of rift valley fever virus (RVFV) induces specific degradation of PKR. 238 Following infection with RVFV there is a dramatic decrease in PKR protein levels with little change in the levels of the mRNA.…”

Section: Degradation Of Pkrmentioning

confidence: 99%

Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery

Roberts

Jopling

Jackson

et al. 2009

Progress in Molecular Biology and Translational Science

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Viruses do not carry their own protein biosynthesis machinery and the translation of viral proteins therefore requires that the virus usurps the machinery of the host cell. To allow optimal translation of viral proteins at the expense of cellular proteins, virus families have evolved a variety of methods to repress the host translation machinery, while allowing effective viral protein synthesis. Many viruses use noncanonical mechanisms that permit translation of their own RNAs under these conditions. Viruses have also developed mechanisms to evade host innate immune responses that would repress translation under conditions of viral infection, in particular PKR activation in response to double-stranded RNA (dsRNA). Importantly, the study of viral translation mechanisms has enormously enhanced our understanding of many aspects of the cellular protein biosynthesis pathway and its components. A number of unusual mechanisms of translation initiation that were first discovered in viruses have since been observed in cellular mRNAs, and it has become apparent that a diverse range of translation mechanisms operates in eukaryotes, allowing subtle regulation of this essential process.

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Degradation of the interferon-induced 68,000-M(r) protein kinase by poliovirus requires RNA

Cited by 82 publications

References 83 publications

The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus

The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus

Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

Chapter 9 Viral Strategies to Subvert the Mammalian Translation Machinery

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