Ciborowski Pawel, Kadiu Irena, Rozek Wojciech, Smith Lynette, Bernhardt Kristen, Fladseth Melissa, Ricardo-Dukelow Mary, Gendelman Howard E
Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5800, USA.
Virology. 2007 Jun 20;363(1):198-209. doi: 10.1016/j.virol.2007.01.013. Epub 2007 Feb 22.
Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.
单核吞噬细胞（骨髓单核细胞衍生的巨噬细胞、肺泡巨噬细胞、血管周围巨噬细胞和小胶质细胞）是1型人类免疫缺陷病毒（HIV-1）的储存库和传播载体。病毒如何改变单核吞噬细胞的免疫调节活性以完成其生命周期并影响疾病，目前尚不完全清楚。为了更好地理解病毒对巨噬细胞功能的影响，我们使用一维电泳和液相色谱串联质谱法分析了HIV-1感染的人类单核细胞衍生巨噬细胞的分泌蛋白组。我们在对照（未感染）和病毒感染细胞的培养上清液中鉴定出110种蛋白质。通过蛋白质印迹试验发现并验证了差异表达的细胞骨架、酶、氧化还原和免疫调节蛋白类别。这些包括但不限于胱抑素C、胱抑素B、几丁质酶3样1蛋白、丝切蛋白-1、l-肌动蛋白、超氧化物歧化酶、白三烯A（4）水解酶和α-烯醇化酶。本研究使用独特的蛋白质组学平台，为病毒-宿主细胞相互作用提供了新的见解，这些相互作用可能影响巨噬细胞在HIV疾病中的功能作用。
