Virus-Cell Interactions

Mouland, Andrew J.; Gatignol, Anne; Heveker, Nikolaus

doi:10.1002/3527600906.mcb.200500031

Cited by 4 publications

(4 citation statements)

References 181 publications

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“…The HIV-1 Tat protein is also an inhibitor of PKR acting by substrate competition [ 31 ]. Besides direct viral countermeasures, viruses also evolved to replicate in cells that have the appropriate cellular components to allow their replication [ 70 ]. Viruses can also induce the production of cellular proteins that will counteract an antiviral cell response.…”

Section: Discussionmentioning

confidence: 99%

The PKR activator, PACT, becomes a PKR inhibitor during HIV-1 replication

et al. 2013

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BackgroundHIV-1 translation is modulated by the activation of the interferon (IFN)-inducible Protein Kinase RNA-activated (PKR). PKR phosphorylates its downstream targets, including the alpha subunit of the eukaryotic translation Initiation Factor 2 (eIF2α), which decreases viral replication. The PKR Activator (PACT) is known to activate PKR after a cellular stress. In lymphocytic cell lines, HIV-1 activates PKR only transiently and not when cells replicate the virus at high levels. The regulation of this activation is due to a combination of viral and cellular factors that have been only partially identified.ResultsPKR is transiently induced and activated in peripheral blood mononuclear cells after HIV-1 infection. The addition of IFN reduces viral replication, and induces both the production and phosphorylation of PKR. In lymphocytic Jurkat cells infected by HIV-1, a multiprotein complex around PKR contains the double-stranded RNA binding proteins (dsRBPs), adenosine deaminase acting on RNA (ADAR)1 and PACT. In HEK 293T cells transfected with an HIV-1 molecular clone, PACT unexpectedly inhibited PKR and eIF2α phosphorylation and increased HIV-1 protein expression and virion production in the presence of either endogenous PKR alone or overexpressed PKR. The comparison between different dsRBPs showed that ADAR1, TAR RNA Binding Protein (TRBP) and PACT inhibit PKR and eIF2α phosphorylation in HIV-infected cells, whereas Staufen1 did not. Individual or a combination of short hairpin RNAs against PACT or ADAR1 decreased HIV-1 protein expression. In the astrocytic cell line U251MG, which weakly expresses TRBP, PACT mediated an increased HIV-1 protein expression and a decreased PKR phosphorylation. In these cells, a truncated PACT, which constitutively activates PKR in non-infected cells showed no activity on either PKR or HIV-1 protein expression. Finally, PACT and ADAR1 interact with each other in the absence of RNAs.ConclusionIn contrast to its previously described activity, PACT contributes to PKR dephosphorylation during HIV-1 replication. This activity is in addition to its heterodimer formation with TRBP and could be due to its binding to ADAR1. 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 and increased replication.

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Section: Discussionmentioning

confidence: 99%

The PKR activator, PACT, becomes a PKR inhibitor during HIV-1 replication

et al. 2013

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“…Specific molecular events between viral and cellular components mediate viral entry, trafficking, expression and release [24]. Some aspects of these virus-host relationships have been addressed.…”

Section: Introductionmentioning

confidence: 99%

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et al. 2007

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New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.

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“…Both Tat protein and VA RNAs inhibit Dicer activity. A striking feature of RNAi suppressors characterized thus far from mammalian viruses is that most are also inhibitors of PKR, either by direct binding, by RNA sequestration or by substrate competition [ 14 ]. However, this feature is not shared by plant and insect silencing suppressors.…”

mentioning

confidence: 99%

“…Because RNAi is a mechanism that cleaves RNAs homologous to defined siRNAs, it should participate to the elimination of unwanted exogenous RNA to protect the cell. However, numerous examples show that viruses also co-opt cellular pathways and use them for their own replication [ 14 ]. Therefore, we cannot exclude that the RNAi pathway can support HIV replication and possibly other viruses.…”

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confidence: 99%