Identification of a Specific miRNA Profile in HIV-Exposed Seronegative Individuals

Yahyaei, Sara; Biasin, Mara; Saulle, Irma; Gnudi, Federica; Luca, Mariacristina De; Tasca, Karen Ingrid; Trabattoni, Daria; Caputo, Sergio Lo; Mazzotta, Francesco; Clerici, Mario

doi:10.1097/qai.0000000000001070

Cited by 20 publications

(19 citation statements)

References 56 publications

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“…Another interesting phenotype in HIV infection resistance is HIV-exposed seronegative individuals (HESN), highly virus-exposed individuals persistently seronegative. The expression profile of 84 miRNA of these patients has been assessed in unstimulated PBMC of HESN, HIV+ individuals, and healthy controls [75]. Interestingly, miR-99a is also upregulated in HESN as we reported in our LTNP.…”

Section: Discussionsupporting

confidence: 55%

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

Ayala-Suárez

Díez-Fuertes

Calonge

et al. 2020

JCM

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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.

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Section: Discussionsupporting

confidence: 55%

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

Ayala-Suárez

Díez-Fuertes

Calonge

et al. 2020

JCM

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“…These data suggest that the IL-21/miR-29 axis contributes to the control of HIV-1 replication and could be exploited in the design of new therapeutic strategies. Consistently with this observation, we recently showed that miR-29 is highly expressed in plasma and peripheral blood mononuclear cells (PBMCs) of HIV-1 exposed seronegative individuals (HESN), suggesting a role of this miRNA in the natural resistance to HIV-1 infection [19]. Based on these premises we performed an in-depth analysis of the possible role played by the IL-21/miR-29 axis in the natural resistance to HIV-1 infection observed in HESN.…”

Section: Introductionsupporting

confidence: 66%

“…Second, IL-21 triggers antiviral humoral response by enhancing B cell functions in both chronically SIV-infected rhesus macaques [27] and humans [2,[28][29][30]. Third, IL-21 elicits the STAT3dependent expression of miR-29 [13], a miRNA family which plays a crucial role in thwarting HIV-1 replication [15] and whose expression is significantly augmented in HESN PBMCs [19]. In our experimental setting, no significant difference were detected in perforin and granzyme expression in any of the analysed conditions.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 21 (IL-21)/microRNA-29 (miR-29) axis is associated with natural resistance to HIV-1 infection

Ortega

Saulle

Mercurio

et al. 2018

Aids

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“…Although all three theories may be correct there is increasing evidence that ex-miRNA are functional, can be passed between leukocytes in vitro and in vivo , and play a role in disease ( 161 – 164 ). Supporting a functional role is the finding that, miR-233 and miR-29a are upregulated in the serum, and unstimulated PBMCs of HIV-exposed seronegative individuals (HESN) compared with healthy controls ( 165 ). PBMCs from HESN individuals release greater amounts of miR-223 and miR-29a when infected with HIV in vitro and infection is also better controlled, prompting the study’s authors to speculate that miR-223 and miR-29a could represent novel therapeutic targets.…”

Section: Extracellular Mirnas and Host Response To Pathogensmentioning

confidence: 99%

The Clinical Application of MicroRNAs in Infectious Disease

2017

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MicroRNAs (miRNAs) are short single-stranded non-coding RNA sequences that posttranscriptionally regulate up to 60% of protein encoding genes. Evidence is emerging that miRNAs are key mediators of the host response to infection, predominantly by regulating proteins involved in innate and adaptive immune pathways. miRNAs can govern the cellular tropism of some viruses, are implicated in the resistance of some individuals to infections like HIV, and are associated with impaired vaccine response in older people. Not surprisingly, pathogens have evolved ways to undermine the effects of miRNAs on immunity. Recognition of this has led to new experimental treatments, RG-101 and Miravirsen—hepatitis C treatments which target host miRNA. miRNAs are being investigated as novel infection biomarkers, and they are being used to design attenuated vaccines, e.g., against Dengue virus. This comprehensive review synthesizes current knowledge of miRNA in host response to infection with emphasis on potential clinical applications, along with an evaluation of the challenges still to be overcome.

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Identification of a Specific miRNA Profile in HIV-Exposed Seronegative Individuals

Cited by 20 publications

References 56 publications

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

Interleukin 21 (IL-21)/microRNA-29 (miR-29) axis is associated with natural resistance to HIV-1 infection

The Clinical Application of MicroRNAs in Infectious Disease

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