Haverland Nicole A, Fox Howard S, Ciborowski Pawel
Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center , Durham Research Center I, 985800 Nebraska Medical Center Omaha, Nebraska 68198-5800, United States.
J Proteome Res. 2014 Apr 4;13(4):2109-19. doi: 10.1021/pr4012602. Epub 2014 Mar 10.
Human immunodeficiency virus type 1 (HIV-1) infection remains a worldwide epidemic, and innovative therapies to combat the virus are needed. Developing a host-oriented antiviral strategy capable of targeting the biomolecules that are directly or indirectly required for viral replication may provide advantages over traditional virus-centric approaches. We used quantitative proteomics by SWATH-MS in conjunction with bioinformatic analyses to identify host proteins, with an emphasis on nucleic acid binding and regulatory proteins, which could serve as candidates in the development of host-oriented antiretroviral strategies. Using SWATH-MS, we identified and quantified the expression of 3608 proteins in uninfected and HIV-1-infected monocyte-derived macrophages. Of these 3608 proteins, 420 were significantly altered upon HIV-1 infection. Bioinformatic analyses revealed functional enrichment for RNA binding and processing as well as transcription regulation. Our findings highlight a novel subset of proteins and processes that are involved in the host response to HIV-1 infection. In addition, we provide an original and transparent methodology for the analysis of label-free quantitative proteomics data generated by SWATH-MS that can be readily adapted to other biological systems.
1型人类免疫缺陷病毒（HIV-1）感染仍是一种全球性流行病，因此需要创新疗法来对抗这种病毒。开发一种以宿主为导向的抗病毒策略，该策略能够靶向病毒复制直接或间接所需的生物分子，可能比传统的以病毒为中心的方法具有优势。我们使用SWATH-MS定量蛋白质组学结合生物信息学分析来鉴定宿主蛋白，重点是核酸结合蛋白和调节蛋白，这些蛋白可作为开发以宿主为导向的抗逆转录病毒策略的候选物。使用SWATH-MS，我们鉴定并定量了未感染和HIV-1感染的单核细胞衍生巨噬细胞中3608种蛋白质的表达。在这3608种蛋白质中，有420种在HIV-1感染后发生了显著变化。生物信息学分析揭示了RNA结合和加工以及转录调控的功能富集。我们的研究结果突出了宿主对HIV-1感染反应中涉及的一组新的蛋白质和过程。此外，我们提供了一种原始且透明的方法，用于分析由SWATH-MS生成的无标记定量蛋白质组学数据，该方法可轻松应用于其他生物系统。
