Seeking “protective” and “harmful” immune genes during chronic HIV-1 infection by transcriptome analysis

Lingyan Zhu, C. Qiu, C. Qiu, Ying Wang, Yuan Dong, Linxia Zhang, Weihui Fu, Jun Wei, Xiaoyan Zhang, Jianqing Xu
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Abstract

Abstract Human immunodeficiency virus (HIV)-infected individuals exhibit remarkable transcriptomic variation. Transcriptome analyses of antiretroviral therapy (ART)-free chronically infected HIV-1 patients with different clinical outcomes are likely to aid the development of vaccine and immune therapies. Here, we performed microarray analyses on whole-blood derived RNA from 89 ART-free HIV-1-infected individuals from 2 cohorts. The differentially expressed genes were analyzed between long-term non-progressors, viremic non-progressors and typical progressors, and between elite controllers and non-elite controllers among the long-term non-progressors. Several genes related to T-cell growth, proliferation and differentiation and antiapoptosis were upregulated, whereas interferon-stimulated genes and inflammatory genes were significantly downregulated in long-term non-progressors and viremic non-progressors. The observations above were further confirmed in the set of 261 genes that correlated with disease progression during a 5-year follow-up, which included 51 genes significantly associated with slower disease progression, and 210 genes associated with aggressive disease progression. Overall, our data suggest that it is vital to maintain the homeostasis of the immune system when mounting antiviral immune responses. Immune therapeutics able to reconstruct immune homeostasis are likely to be required for immune reconstitution in the context of ART, such as the administration of interleukin-7, healthy allogenic CD4+ T cells (providing CD4+ T-cell growth factors), or Tregs.
通过转录组分析寻找慢性HIV-1感染过程中的“保护性”和“有害”免疫基因
人类免疫缺陷病毒(HIV)感染个体表现出显著的转录组变异。对无抗逆转录病毒治疗(ART)的不同临床结果的慢性感染HIV-1患者的转录组分析可能有助于疫苗和免疫疗法的开发。在这里,我们对来自2个队列的89名无art的hiv -1感染者的全血来源RNA进行了微阵列分析。分析了长期无进展者、病毒血症无进展者和典型进展者以及长期无进展者中精英控制者和非精英控制者之间的差异表达基因。一些与t细胞生长、增殖、分化和抗凋亡相关的基因被上调,而在长期非进展者和病毒血症非进展者中,干扰素刺激基因和炎症基因被显著下调。在5年随访期间,上述观察结果在261个与疾病进展相关的基因中得到进一步证实,其中51个基因与疾病进展较慢显著相关,210个基因与疾病进展积极相关。总的来说,我们的数据表明,在进行抗病毒免疫反应时,维持免疫系统的稳态至关重要。在抗逆转录病毒治疗的背景下,免疫重建可能需要能够重建免疫稳态的免疫疗法,例如给药白介素-7、健康的同种异体CD4+ T细胞(提供CD4+ T细胞生长因子)或Tregs。
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