HIV-1 translation and its regulation by cellular factors PKR and PACT

Burugu, Samantha; Daher, Aı̈cha; Meurs, Éliane; Gatignol, Anne

doi:10.1016/j.virusres.2014.07.014

Cited by 25 publications

(17 citation statements)

References 235 publications

(307 reference statements)

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“…Staufen promotes Gag oligomerization and virion RNP encapsidation, processes essential to viral replication (Chatel-Chaix et al, 2004; Ghoujal et al, 2012; Mouland et al, 2000). The isolation of EIF2AK2 (protein kinase R, PKR) is of interest given that NF90/45, TRBP, eIF2α and DHX9 are substrates for phosphorylation by PKR (Burugu et al, 2014). PKR’s activity is central to innate antiviral response by phosphorylating eIF2α and attenuating viral mRNA translation (Burugu et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…The isolation of EIF2AK2 (protein kinase R, PKR) is of interest given that NF90/45, TRBP, eIF2α and DHX9 are substrates for phosphorylation by PKR (Burugu et al, 2014). PKR’s activity is central to innate antiviral response by phosphorylating eIF2α and attenuating viral mRNA translation (Burugu et al, 2014). Notably, eIF2α-phosphorylation was not detectable in HIV-1 infected lymphocytes (Sharma et al, 2012), which may be attributable to viral antagonism of PKR activity.…”

Section: Resultsmentioning

confidence: 99%

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HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Stake

Singh

et al. 2015

Virology

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Essential host cofactors in retrovirus replication bind cis-acting sequences in 5’untranslated region (UTR). Although host RBPs are crucial to all aspects of virus biology, elucidating their roles in replication remains a challenge to the field. Here RNA affinity-coupled-proteomics generated a comprehensive, unbiased inventory of human and avian RNA binding proteins (RBPs) co-isolating with 5’UTRs of HIV-1, spleen necrosis virus and Rous sarcoma virus. Applying stringent biochemical and statistical criteria, we identified 185 RBP; 122 were previously implicated in retrovirus biology and 63 are new to the 5’UTR proteome. RNA electrophoretic mobility assays investigated paralogs present in the common ancestor of vertebrates and one hnRNP was identified central node to the biological process-anchored networks of HIV-1, SNV, and RSV 5’ UTR-proteomes. This comprehensive view of the host constituents of retroviral RNPs is broadly applicable to investigation of viral replication and antiviral response in both human and avian cell lineages.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Stake

Singh

et al. 2015

Virology

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“…Moreover, PACT contributes to PKR dephosphorylation during HIV-1 replication probably due to its binding to ADAR1 [234]. Thus, HIV-1 has evolved to replicate in cells with high levels of TRBP, to induce the expression of ADAR1 and to change the function of PACT for PKR inhibition [235].…”

Section: Pkrmentioning

confidence: 99%

Early IFN type I response: Learning from microbial evasion strategies

Coccia

Battistini

2015

Seminars in Immunology

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Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease. In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies.

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“…One of the ISG products is PKR (protein kinase, RNA-activated), a protein kinase that plays a central role in regulating the outcome of a viral infection [9][10][11]. In virally infected cells, PKR is activated by binding to dsRNA (double-stranded RNA), a product of several viral infections, including HIV-1 [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…During HIV-1 infection, TRBP inhibits PKR activation by sequestration of the activating TAR RNA and by direct interaction with PKR's two dsRNA-binding motifs [21][22][23]. Although TRBP is an effective inhibitor of PKR, HIV-1 has evolved additional mechanisms to more effectively block PKR activity and successfully replicate in infected cells [10,24].…”

Section: Introductionmentioning

confidence: 99%

ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element

Chukwurah

Handy

Patel

2017

Biochemical Journal

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Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase PKR, which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor eIF2α. This shuts down the synthesis of both host and viral proteins, allowing the cell to mount an effective antiviral response. PACT (protein activator of PKR) is a cellular protein activator of PKR, primarily functioning to activate PKR in response to cellular stress. Recent studies have indicated that during HIV-1 infection, PACT's normal cellular function is compromised and that PACT is unable to activate PKR. Using various reporter systems and in vitro kinase assays, we establish in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. Our results highlight an important pathway by which HIV-1 transcripts subvert the host cell's antiviral activities to enhance their translation.

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HIV-1 translation and its regulation by cellular factors PKR and PACT

Cited by 25 publications

References 235 publications

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Early IFN type I response: Learning from microbial evasion strategies

ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element

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