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

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.