【正文】 n Upregulation Unchange Virus infection Genomics analysis: an integrated approach Overview of gene expression in PBMCs from variolainfected macaques. A total of 2,387 elements displayed ≥3fold change in mRNA expression. Data from individual elements or genes are represented as a single row, and different time points in the time courses (triangles) are shown as columns. Red and green denote expression levels greater or less, respectively, than baseline values (average of two to four samples taken at days 4 and 0 before inoculation). Proc Natl Acad Sci U S A. 2022, 19。 101(42): 15190–15195. Transcription of host RNAP II genes is repressed following HSV1 infection. (A and B) Nuclear runon transcription analysis of cellular and viral gene transcription in HeLa cells infected with wildtype virus, . (C) Abundance of RNAP II and GTFs in mockinfected and HSV1infected cells. J Virol 1997, 71(3):203140. J Virol 2022,75(20):987284. 細(xì)胞 mRNA↓ 病毒 mRNA↑ Cell molecular responses to viruses ?Responses to viral attachment: activate or block signaling cascade ?Viral modulation of host cell transcription ?Viral modulation of host cell protein synthesis Virusinduced shutoff of host cell protein synthesis. Murine NIH 3T3 cells (lanes 1 to 4) orMadinDarby bovine kidney cells (lanes 5 and 6) were mock infected (U) or infected (I), respectively, with EMCV (lanes 1 and 2), VSV (lanes 3 and 4), or in?uenza virus (lanes 5 and 6). Microbiol Mol Biol Rev 2022, 64(2):23980. 細(xì)胞 蛋白 ↓ 病毒蛋白 ↑ 病毒抑制宿主細(xì)胞蛋白質(zhì)合成的機(jī)制 ? 競爭機(jī)制 (VSV) ?大量的病毒 mRNA ?病毒 mRNA與核糖復(fù)合體親和力高 ? 抑制宿主細(xì)胞 mRNA從胞核向胞漿轉(zhuǎn)運(yùn) (Adenovirus) ? 促進(jìn)宿主細(xì)胞 mRNA降解 (HSV) ? 抑制細(xì)胞 mRNA翻譯的起始和延伸 (Poliovirus) Schematic illustration of eukaryotic mRNA translation and major sites of viral regulation. Microbiol Mol Biol Rev 2022, 64(2):23980. 內(nèi)部核糖體進(jìn)入位點(diǎn) (IRES, internal ribosome entry site)是 mRNA 5‘端非編碼區(qū)的一段特殊 RNA結(jié)構(gòu)元件，允許核糖體不依賴帽子結(jié)構(gòu)，而是直接與此序列結(jié)合，并啟動翻譯。 Poliovirus genome (+ssRNA), including an IRES. 1988 Viral proteases ? Modi?cations of eIF4GI during viral infections. Biology of the Cell 2022, 95:141–156 Cellular proteome Viral proteome 蛋白質(zhì)組學(xué)分析 Analysis of virion/cell position by mass spectrometry. Typical approaches for analyzing virion or cell protein position 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(xué)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(xì)胞結(jié)構(gòu)改變 ? 細(xì)胞表型