Abstract
Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.
Highlights
HIV natural infection is characterized by continued viral replication, systemic chronic immune activation, and a strong decline of CD4+ T cells
This group is divided into two subgroups (n = 8) according to their capacity to control viral replication: elite controllers long-term non-progressors (LTNP) (EC-LTNP), defined as those with undetectable viremia or viral load < 2000 copies of viral RNA/mL in less than 25% of determinations during the follow-up, and viremic LTNP that includes the other individuals with a viral load below 10,000 copies/mL in all the determinations during the follow-up
After two years of antiretroviral therapy (ART), viral load declined below the detection level (
Summary
HIV natural infection is characterized by continued viral replication, systemic chronic immune activation, and a strong decline of CD4+ T cells. The introduction of antiretroviral therapy (ART) allowed the control of AIDS manifestation, but HIV infection remains incurable [1]. On that basis, unraveling new mechanisms to control the infection is of the essence to develop new therapeutic approaches in chasing a functional cure. Long-term non-progressors (LTNP) and elite controllers (EC) have been extensively studied, due to their ability to maintain high CD4+ T cell levels and undetectable viral load in plasma, respectively, for a long time in the absence of ART [2]. It is widely considered that both phenotypes represent excellent natural model scenarios of immune control of viral infection
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