<scp>NF</scp>90 is a novel influenza A virus <scp>NS</scp>1‐interacting protein that antagonizes the inhibitory role of <scp>NS</scp>1 on <scp>PKR</scp> phosphorylation

Li, Ting; Li, Xi; Zhu, Wenfei; Wang, HuiYu; Mei, Lin; Wu, Shaoqiang; Lin, Xiaoyang; Han, Xiao

doi:10.1002/1873-3468.12311

Cited by 20 publications

(26 citation statements)

References 70 publications

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“…This is not surprising given the role of NS1 in host-shut-off as well as in protecting the viral RNA from recognition by RNA sensors in the cell (see above), thereby preventing the activation of PKR and concomitant eiF2alpha phosphorylation and stress granule formation. Interestingly, this innate immune evasion activity of NS1 is counteracted by cellular protein NF90, which partly prevents the suppression of PKR triggered stress granule formation by NS1 by binding both PKR and NS1 [105]. Besides NS1, the influenza nucleoprotein NP and polymerase subunit PA-X help to prevent stress granule formation, due to their RNA protection and host-shut off functions, respectively [103].…”

Section: Manipulation Of Stress Granule Formationmentioning

confidence: 99%

Innate Immune Evasion by Human Respiratory RNA Viruses

2019

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The impact of respiratory virus infections on the health of children and adults can be very significant. Yet, in contrast to most other childhood infections as well as other viral and bacterial diseases, prophylactic vaccines or effective antiviral treatments against viral respiratory infections are either still not available, or provide only limited protection. Given the widespread prevalence, a general lack of natural sterilizing immunity, and/or high morbidity and lethality rates of diseases caused by influenza, respiratory syncytial virus, coronaviruses, and rhinoviruses, this difficult situation is a genuine societal challenge. A thorough understanding of the virushost interactions during these respiratory infections will most probably be pivotal to ultimately meet these challenges. This review attempts to provide a comparative overview of the knowledge about an important part of the interaction between respiratory viruses and their host: the arms race between host innate immunity and viral innate immune eva-

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Section: Manipulation Of Stress Granule Formationmentioning

confidence: 99%

Innate Immune Evasion by Human Respiratory RNA Viruses

2019

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“…Usually, ILF2 forms a heterodimeric complex with ILF3, which is shown to be implicated in DNA repair [43], gene transcription [44], microRNA processing [45, 46], and mRNA translation [47, 48]. Moreover, ILF2, ILF3 or the ILF2/ILF3 heterodimer has also been involved in various virus life cycle including hepatitis C virus (HCV) [49], infectious bursal disease virus (IBDV) [50], poliovirus [51], influenza virus [52, 53], dengue virus [54], human immunodeficiency virus type 1 (HIV-1) [55], human T-cell leukemia virus [56], as well as in the host defense mechanism protecting from viral infections [57]. Our previous study has screened that ILF3 interacts with the nsp2 of PRRSV JXwn06 [58].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-2 enhancer binding factor 2 interacts with the nsp9 or nsp2 of porcine reproductive and respiratory syndrome virus and exerts negatively regulatory effect on the viral replication

Wen

Bian

Zhang

et al. 2017

Virol J

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BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failures in sows and respiratory diseases in growing pigs, resulting in huge economic loss for the pig production worldwide. The nonstructural protein 9 (nsp9) and nonstructural protein 2 (nsp2) of PRRSV are known to play important roles in viral replication. Cellular interleukin-2 enhancer binding factor 2 (ILF2) participates in many cellular pathways and involves in life cycle of some viruses. In the present study, we analyzed the interaction of cellular ILF2 with the nsp9 and nsp2 of PRRSV in vitro and explored the effect of ILF2 on viral replication.MethodsThe interaction of ILF2 with the nsp9 or nsp2 of PRRSV was analyzed in 293FT cells and MARC-145 cells by co-immunoprecipitation (Co-IP) and the co-localization of ILF2 with the nsp9 or nsp2 of PRRSV in MARC-145 cell and pulmonary alveolar macrophages (PAMs) was examined by confocal immunofluorescence assay. The effect of ILF2 knockdown and over-expression on PRRSV replication was explored in MARC-145 cells by small interfering RNA (siRNA) and lentivirus transduction, respectively.ResultsThe interaction of ILF2 with nsp9 or nsp2 was first demonstrated in 293FT cells co-transfected with ILF2-expressing plasmid and nsp9-expressing plasmid or nsp2-expressing plasmid. The interaction of endogenous ILF2 with the nsp9 or nsp2 of PRRSV was further confirmed in MARC-145 cells transduced with GFP-nsp9-expressing lentiviruses or infected with PRRSV JXwn06. The RdRp domain of nsp9 was shown to be responsible for its interaction with ILF2, while three truncated nsp2 were shown to interact with ILF2. Moreover, we observed that ILF2 partly translocated from the nucleus to the cytoplasm and co-localized with nsp9 and nsp2 in PRRSV-infected MARC-145 cells and PAMs. Finally, our analysis indicated that knockdown of ILF2 favored the replication of PRRSV, while over-expression of ILF2 impaired the viral replication in MARC-145 cells.ConclusionOur findings are the first to confirm that the porcine ILF2 interacts with the nsp9 and nsp2 of PRRSV in vitro, and exerts negatively regulatory effect on the replication of PRRSV. Our present study provides more evidence for understanding the roles of the interactions between cellular proteins and viral proteins in the replication of PRRSV.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-017-0794-5) contains supplementary material, which is available to authorized users.

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“…Nuclear factor 90 (NF90) regulates gene expression at transcriptional, post-transcriptional and translation levels by binding miRNAs or modulating the translocation or translation of mRNAs (Jayachandran et al 2016). More recently, NF90 was shown to exert an antiviral activity since NF90 knockout led to enhanced viral sensitivity (Wen et al 2014;Li et al 2016). This has been attributed to NF90's involvement in several host antiviral mechanisms, including relief of PKR inhibition by viral proteins (Wen et al 2014;Li et al 2016).…”

Section: Proteins That Target the Pkr Regulatory Domainmentioning

confidence: 99%

“…More recently, NF90 was shown to exert an antiviral activity since NF90 knockout led to enhanced viral sensitivity (Wen et al 2014;Li et al 2016). This has been attributed to NF90's involvement in several host antiviral mechanisms, including relief of PKR inhibition by viral proteins (Wen et al 2014;Li et al 2016). Indeed, influenza A virus produces a nonstructural protein 1 (NS1) that inhibits PKR through direct dsRBM binding and/or RNA sequestration.…”

Section: Proteins That Target the Pkr Regulatory Domainmentioning

confidence: 99%

The search for a PKR code—differential regulation of protein kinase R activity by diverse RNA and protein regulators

Bou‐Nader

Gordon

Henderson

et al. 2019

RNA

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The interferon-inducible protein kinase R (PKR) is a key component of host innate immunity that restricts viral replication and propagation. As one of the four eIF2α kinases that sense diverse stresses and direct the integrated stress response (ISR) crucial for cell survival and proliferation, PKR's versatile roles extend well beyond antiviral defense. Targeted by numerous host and viral regulators made of RNA and proteins, PKR is subject to multiple layers of endogenous control and external manipulation, driving its rapid evolution. These versatile regulators include not only the canonical doublestranded RNA (dsRNA) that activates the kinase activity of PKR, but also highly structured viral, host, and artificial RNAs that exert a full spectrum of effects. In this review, we discuss our deepening understanding of the allosteric mechanism that connects the regulatory and effector domains of PKR, with an emphasis on diverse structured RNA regulators in comparison to their protein counterparts. Through this analysis, we conclude that much of the mechanistic details that underlie this RNA-regulated kinase await structural and functional elucidation, upon which we can then describe a "PKR code," a set of structural and chemical features of RNA that are both descriptive and predictive for their effects on PKR.

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NF90 is a novel influenza A virus NS1‐interacting protein that antagonizes the inhibitory role of NS1 on PKR phosphorylation

Cited by 20 publications

References 70 publications

Innate Immune Evasion by Human Respiratory RNA Viruses

Innate Immune Evasion by Human Respiratory RNA Viruses

Interleukin-2 enhancer binding factor 2 interacts with the nsp9 or nsp2 of porcine reproductive and respiratory syndrome virus and exerts negatively regulatory effect on the viral replication

The search for a PKR code—differential regulation of protein kinase R activity by diverse RNA and protein regulators

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