【正文】 by MALDITOF (matrixassisted laser desorption ionization–time of flight) mass spectrometry and LCMS/MS (liquid chromatographylinked tandem mass spectrometry). Microbiol Mol Biol Rev 2022, 71(2):398411 ? Cellular proteome Viral proteome Proteinprotein Interaction 蛋白質(zhì)組學分析 Visualization of the HIV1 human protein interaction work. Colored circles represent human proteins and are shown clustering around the HIV1 protein they interact with. Human proteins that interact with multiple viral proteins are shown toward the center of the image rather than clustered around a specific HIV1 protein. AIDS Res Hum Retroviruses. 2022, 24(12): 1497–1502. Identification of 1448 human proteins that interact with HIV1 prising 2589 unique HIV1tohuman protein interactions. Preliminary analysis of the extracted data indicates 32% were direct physical interactions (., binding) and 68% were indirect interactions (., upregulation through activation of signaling pathways). AIDS Res Hum Retroviruses. 2022, 24(12): 1497–1502. ? 分子水平變化 ? 細胞結(jié)構(gòu)改變 ? 細胞表型改變 ? 信號途徑 ? DNA復制 ? 轉(zhuǎn)錄 ? 翻譯 ? 細胞膜改變 ? 包涵體 ? 細胞骨架改變 ? 細胞死亡 ? 細胞周期抑制 ? 細胞融合 ? 細胞轉(zhuǎn)化 ? 穩(wěn)定狀態(tài)感染 Cell structure changes ?病毒誘導的細胞膜結(jié)構(gòu)改變（ Virusinduced alterations in cellular membrances） ? 封閉和下調(diào)細胞表面的病毒受體 ? 調(diào)節(jié) MHC 的表達 ? 病毒蛋白質(zhì)發(fā)揮離子通道的功能 ? Vpu, Nef and Vpu prevent cell surface expression of CD4 by different mechanisms. The viral glycoprotein Env (gray) binds to the cellular receptor CD4 (green) during transport in the ER. Vpu also binds to CD4 in the ER and targets it for degradation (green fragments) by recruitment to the ubiquitinproteasome pathway through interactions with bTrCP and Skp1p. Nef removes preexisting CD4 from the cell surface by recruiting CD4 into clathrincoated pits, and ultimately into degradative lysosomes, through interactions with the AP2 adaptor plex. ? Science 1998,280:18801884. The MHC class I antigen presentation pathway. Immunology 2022,110:163169. ? Viral inhibition of the MHC class I antigen presentation pathway. Immunology 2022,110:163169. HCMV US2,3,6,10,11 HSV ICP47 Adenovirus E19 HHV7 U21 HHV8 K3, K5 HIV1 Nef Influenza A Virus M2 protein as proton transporter. M2TM exists in two conformational ensembles. In the OpenoutClosedin conformation the Val27 gate is open and the His37 gate is closed whereas the reverse is true for ClosedoutOpenin conformation. At high pH out, the OpenoutClosedin conformation is favored, because pH out decreases the His37 residues get protonated and channel is activated at Kact favoring the ClosedoutOpenin conformation. Release of protons into the viral interior and deprotonation of His37 stabilizes the OpenoutClosedin conformation and the cycle is repeated until equilibration. PNAS 2022, 106(4):106974. Cell structure changes ?包涵體（ Inclusion body） Inclusion bodies are nuclear or cytoplasmic aggregates of stainable substances, usually proteins. They typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins. Rabies: Negri bodies HSV, VZV： Cowdry bodies Cell structure changes ? 細胞骨架 The main cytoskeleton ponents participating to host cell/virus interaction。 6. 細胞受體在宿主物種間的差異可能限制了病毒的宿主范圍。 2. 不同的病毒采用不同的細胞受體。病毒與宿主相互作用 李怡璇 What is a virus ? A