Kottilil Shyam, Yan Michael Y, Reitano Kristin N, Zhang Xiaozhen, Lempicki Richard, Roby Gregg, Daucher Marybeth, Yang Jun, Cortez Karoll J, Ghany Marc, Polis Michael A, Fauci Anthony S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Hepatology. 2009 Jul;50(1):34-45. doi: 10.1002/hep.23055.
Coinfection with hepatitis C virus (HCV) is present in one-third of all human immunodeficiency virus (HIV)-infected individuals in the United States and is associated with rapid progression of liver fibrosis and poor response to pegylated interferon (IFN) and ribavirin. In this study we examined gene expression profiles in peripheral blood mononuclear cells (PBMCs) from different groups of individuals who are monoinfected or coinfected with HIV and HCV. Data showed that HIV and HCV viremia up-regulate genes associated with immune activation and immunoregulatory pathways. HCV viremia is also associated with abnormalities in all peripheral immune cells, suggesting a global effect of HCV on the immune system. Interferon-alpha-induced genes were expressed at a higher level in PBMCs from HIV-infected individuals. HCV and HIV infections leave distinct profiles or gene expression of immune activation in PBMCs. HIV viremia induces an immune activated state; by comparison, HCV infection induces immunoregulatory and proinflammatory pathways that may contribute to progression of liver fibrosis.
An aberrant type-I IFN response seen exclusively in HIV-infected individuals could be responsible for the poor therapeutic response experienced by HIV/HCV coinfected individuals receiving interferon-alpha-based current standard of care.
在美国，三分之一的人类免疫缺陷病毒（HIV）感染者同时感染丙型肝炎病毒（HCV），这与肝纤维化的快速进展以及对聚乙二醇化干扰素（IFN）和利巴韦林的反应不佳有关。在本研究中，我们检测了单纯感染HIV或同时感染HIV和HCV的不同个体组外周血单核细胞（PBMC）中的基因表达谱。数据显示，HIV和HCV病毒血症上调了与免疫激活和免疫调节途径相关的基因。HCV病毒血症还与所有外周免疫细胞的异常有关，提示HCV对免疫系统具有整体影响。α干扰素诱导基因在HIV感染者的PBMC中表达水平更高。HCV和HIV感染在外周血单核细胞中留下了不同的免疫激活特征或基因表达。HIV病毒血症诱导免疫激活状态；相比之下，HCV感染诱导免疫调节和促炎途径，这可能导致肝纤维化进展。
仅在HIV感染者中出现的异常I型干扰素反应可能是接受基于α干扰素的当前标准治疗的HIV/HCV合并感染者治疗反应不佳的原因。
