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10.1371/journal.ppat.1006598 http://scihub22266oqcxt.onion/10.1371/journal.ppat.1006598 C5597281!5597281!28859166     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+Pathog 2017 ; 13 (8): ä Nephropedia Template TP {{tp|p=28859166|t=2017. Primate lentiviruses use at least three alternative strategies to suppress NF-?B-mediated immune activation |pdf=|usr=}}{{28859166}} gab.com Text Primate lentiviruses use at least three alternative strategies to suppress NF- B-mediated immune activation JO: PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=28859166 #FOAvip Primate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. For example, HIV-2 and most simian immunodeficiency viruses (SIVs) use their accessory protein Nef to prevent T cell activation and antiviral gene expression by downmodulating the T cell receptor CD3. This Nef function was lost in HIV-1 and other vpu-encoding viruses suggesting that the acquisition of Vpu-mediated NF-?B inhibition reduced the selection pressure for inhibition of T cell activation by Nef. To obtain further insights into the modulation of NF-?B activity by primate lentiviral accessory factors, we analyzed 32 Vpr proteins from a large panel of divergent primate lentiviruses. We found that those of SIVcol and SIVolc infecting Colobinae monkeys showed the highest efficacy in suppressing NF-?B activation. Vpr-mediated inhibition of NF-?B resulted in decreased IFN? promoter activity and suppressed type I IFN induction in virally infected primary cells. Interestingly, SIVcol and SIVolc differ from all other primate lentiviruses investigated by the lack of both, a vpu gene and efficient Nef-mediated downmodulation of CD3. Thus, primate lentiviruses have evolved at least three alternative strategies to inhibit NF-?B-dependent immune activation. Functional analyses showed that the inhibitory activity of SIVolc and SIVcol Vprs is independent of DCAF1 and the induction of cell cycle arrest. While both Vprs target the IKK complex or a factor further downstream in the NF-?B signaling cascade, only SIVolc Vpr stabilizes I?B? and inhibits p65 phosphorylation. Notably, only de-novo synthesized but not virion-associated Vpr suppressed the activation of NF-?B, thus enabling NF-?B-dependent initiation of viral gene transcription during early stages of the replication cycle, while minimizing antiviral gene expression at later stages. Our findings highlight the key role of NF-?B in antiviral immunity and demonstrate that primate lentiviruses follow distinct evolutionary paths to modulate NF-?B-dependent expression of viral and antiviral genes. Twit Text FOAVip Primate lentiviruses use at least three alternative strategies to suppress NF- B-mediated immune activation ????PLoS Pathog http://www.kidney.de/pget.php?&tw=1&pmid=28859166 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28859166 #FOAvip English Wikipedia <ref>{{Cite pmid|28859166}}</ref> Primate lentiviruses use at least three alternative strategies to suppress NF-?B-mediated immune activation #MMPMID28859166 Hotter D; Krabbe T; Reith E; Gawanbacht A; Rahm N; Ayouba A; Van Driessche B; Van Lint C; Peeters M; Kirchhoff F; Sauter D PLoS Pathog 2017[Aug]; 13 (8): ä PMID28859166show ga Primate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. For example, HIV-2 and most simian immunodeficiency viruses (SIVs) use their accessory protein Nef to prevent T cell activation and antiviral gene expression by downmodulating the T cell receptor CD3. This Nef function was lost in HIV-1 and other vpu-encoding viruses suggesting that the acquisition of Vpu-mediated NF-?B inhibition reduced the selection pressure for inhibition of T cell activation by Nef. To obtain further insights into the modulation of NF-?B activity by primate lentiviral accessory factors, we analyzed 32 Vpr proteins from a large panel of divergent primate lentiviruses. We found that those of SIVcol and SIVolc infecting Colobinae monkeys showed the highest efficacy in suppressing NF-?B activation. Vpr-mediated inhibition of NF-?B resulted in decreased IFN? promoter activity and suppressed type I IFN induction in virally infected primary cells. Interestingly, SIVcol and SIVolc differ from all other primate lentiviruses investigated by the lack of both, a vpu gene and efficient Nef-mediated downmodulation of CD3. Thus, primate lentiviruses have evolved at least three alternative strategies to inhibit NF-?B-dependent immune activation. Functional analyses showed that the inhibitory activity of SIVolc and SIVcol Vprs is independent of DCAF1 and the induction of cell cycle arrest. While both Vprs target the IKK complex or a factor further downstream in the NF-?B signaling cascade, only SIVolc Vpr stabilizes I?B? and inhibits p65 phosphorylation. Notably, only de-novo synthesized but not virion-associated Vpr suppressed the activation of NF-?B, thus enabling NF-?B-dependent initiation of viral gene transcription during early stages of the replication cycle, while minimizing antiviral gene expression at later stages. Our findings highlight the key role of NF-?B in antiviral immunity and demonstrate that primate lentiviruses follow distinct evolutionary paths to modulate NF-?B-dependent expression of viral and antiviral genes. äPrimate lentiviruses use at least three alternative strategies to supp(epmc).pdf DeepDyve Pubget Overpricing