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10.1038/mtna.2015.29

http://scihub22266oqcxt.onion/10.1038/mtna.2015.29
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suck abstract from ncbi


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pmid26506037
      Mol+Ther+Nucleic+Acids 2015 ; 4 (10 ): e259
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  • Reducing IRF-1 to Levels Observed in HESN Subjects Limits HIV Replication, But Not the Extent of Host Immune Activation #MMPMID26506037
  • Su RC ; Plesniarski A ; Ao Z ; Kimani J ; Sivro A ; Jaoko W ; Plummer FA ; Yao X ; Ball TB
  • Mol Ther Nucleic Acids 2015[Oct]; 4 (10 ): e259 PMID26506037 show ga
  • Cells from women who are epidemiologically deemed resistant to HIV infection exhibit a 40-60% reduction in endogenous IRF-1 (interferon regulatory factor-1), an essential regulator of host antiviral immunity and the early HIV replication. This study examined the functional consequences of reducing endogenous IRF-1 on HIV-1 replication and immune response to HIV in natural HIV target cells. IRF-1 knockdown was achieved in ex vivo CD4(+) T cells and monocytes with siRNA. IRF-1 level was assessed using flow cytometry, prior to infection with HIV-Bal, HIV-IIIB, or HIV-VSV-G. Transactivation of HIV long terminal repeats was assessed by p24 secretion (ELISA) and Gag expression (reverse transcription-polymerase chain reaction (RT-PCR)). The expression of IRF-1-regulated antiviral genes was quantitated with RT-PCR. A modest 20-40% reduction in endogenous IRF-1 was achieved in >87% of ex vivo-derived peripheral CD4(+) T cells and monocytes, resulted in >90% reduction in the transactivation of the HIV-1 genes (Gag, p24) and, hence, HIV replication. Curiously, these HIV-resistant women demonstrated normal immune responses, nor an increased susceptibility to other infection. Similarly, modest IRF-1 knockdown had limited impact on the magnitude of HIV-1-elicited activation of IRF-1-regulated host immunologic genes but resulted in lessened duration of these responses. These data suggest that early expression of HIV-1 genes requires a higher IRF-1 level, compared to the host antiviral genes. Together, these provide one key mechanism underlying the natural resistance against HIV infection and further suggest that modest IRF-1 reduction could effectively limit productive HIV infection yet remain sufficient to activate a robust but transient immune response.
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