20xx年醫(yī)學(xué)專題—hiv發(fā)病機(jī)理(編輯修改稿)
2024-11-17 22:17 本頁(yè)面
【文章內(nèi)容簡(jiǎn)介】 ble, but NMR analysis suggest a direct interaction with Kd ~ mM。 yeast twohybrid assays also suggest an interaction– Acts as a connector to the hostcell endocytic machinery? Colocalizes with AP2 on inner plasma membrane? Conserved dileucine based sorting motif (E/DxxxL?) in Nef is important for both CD4downmodulation and AP2 colocalization? Interacts with NBP1 (identified through a yeast twohybrid screen). NBP1 is part of the vacuolar membrane ATPase plex in clathrincoated pits (H subunit of vacuolar ATPaseVH1)? Cterminal diacidic motif (DD) in Nef is important for NBP1 interaction, and, at least in SIV Nef, the dileucine motif is also important for NBP1 interactions ? ?? May bind to bCop, a coatamer protein which targets proteins to lysosomesNBP1第十二 頁(yè) ，共三十三 頁(yè) 。 of MHC Class I? Advantages:– Immune evasion。 MHC Class I presents antigens to cytotoxic T lymphocytes。 alerts innate and adaptive immune system to virally infected cells? Evidence:– Nef expression reduces susceptibility of HIVinfected cells to CTL mediated lysis in vitro– selectively downregulates only HLAA and HLAB, which presents antigens to CTLs。 – does NOT downregulate HLAC and HLAE, which inhibit NKcell mediated cell lysis – Thus, efficiency of CTLmediated lysis (adaptive immunity) is reduced without increasing increasing susceptibility to NK cell lysisHIVCTLMHC Class IHIV antigen51Cr第十三 頁(yè) ，共三十三 頁(yè) 。E:T ratio% Lysis1:2 1:5 1:10 1:20100%0%HIV wtHIV DnefCTLMHC Class IHIV antigenE (Effector Cell)T (Target Cell)第十四 頁(yè) ，共三十三 頁(yè) 。III. Mediates Cellular Activation and Signaling? Nef expression upregulates a transcriptional program that activates the HIV LTR (microarray analysis)第十五 頁(yè) ，共三十三 頁(yè) 。III. Mediates Cellular Activation and Signaling? Nef expression upregulates a transcriptional program that activates the HIV LTR (microarray analysis)? Nef can induce secretion of paracrine factors that enhance viral replication。 macrophage supernatants from cells transduced with nefexpressing adenoviral vector can facilitate HIV replication in resting lymphoid cultures3 6 9 (days)p24(ng/ml)Advnef supntAdvGFP supnt第十六 頁(yè) ，共三十三 頁(yè) 。III. Mediates Cellular Activation and Signaling? Nef expression upregulates a transcriptional program that activates the HIV LTR (microarray analysis)? Nef can induce secretion of paracrine factors that enhance viral replication。 macrophage supernatants from cells transduced with nefexpressing adenoviral vector can facilitate HIV replication in re
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