Unique microRNA expression in the colonic mucosa during chronic HIV-1 infection

Fulcher, Jennifer A.; Κούκος, Γεώργιος; Κουτσιούμπα, Μαρίνα; Elliott, Julie; Drakaki, Alexandra; Iliopoulos, Dimitrios; Anton, Peter A.

doi:10.1097/qad.0000000000001582

Cited by 6 publications

(3 citation statements)

References 68 publications

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“…In the context of HIV-1 infection, high expression of miRNAs 29a, 28, 125b, 382, 150, 223, 382, 155, 196b and 1290 inhibit viral expression and are associated with maintaining latency in resting primary CD4 + T lymphocytes and macrophages (32-35, 73, 87). Specifically, miR-29a is associated with HIV-1 latency and natural resistance by targeting HIV-1 RNA in the overlapping 3'LTR and Nef sequences (48,71,88,89), whereas its expression is decreased during chronic HIV-1 infection (90). Furthermore, miR155 which contributes to HIV-1 latency in resting CD4 + T lymphocytes is a biomarker of immune activation in PLWH in extracellular vesicles (32,73,91,92).…”

Section: Previous Studies Have Analyzed the Differential Expression O...mentioning

confidence: 99%

The sequestration of miR-642a-3p by a complex formed by HIV-1 Gag and human Dicer increases AFF4 expression and viral production

Alpuche-Lazcano,

Dunkley,

Scarborough

et al. 2023

Preprint

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Micro (mi)RNAs are critical regulators of gene expression in human cells, the functions of which can be affected during viral replication. Here, we show that the human immunodeficiency virus type 1 (HIV-1) structural precursor Gag protein interacts with the miRNA processing enzyme Dicer. RNA immunoprecipitation and sequencing experiments show that Gag modifies the retention of a specific miRNA subset without affecting Dicer’s pre-miRNA processing activity. Among the retained miRNAs, miR-642a-3p shows an enhanced occupancy on Dicer in the presence of Gag and is predicted to target AFF4 mRNA, which encodes an essential scaffold protein for HIV-1 transcriptional elongation. miR-642a-3p gain- or loss-of-function negatively or positively regulates AFF4 protein expression at mRNA and protein levels with concomitant modulations of HIV-1 production, consistent with an antiviral activity. By sequestering miR-642a-3p with Dicer, Gag enhances AFF4 expression and HIV-1 production without affecting miR-642a-3p levels. These results identify miR-642a-3p as a strong suppressor of HIV-1 replication and uncover a novel mechanism by which a viral structural protein directly disrupts an miRNA function for the benefit of its own replication.

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Section: Previous Studies Have Analyzed the Differential Expression O...mentioning

confidence: 99%

The sequestration of miR-642a-3p by a complex formed by HIV-1 Gag and human Dicer increases AFF4 expression and viral production

Alpuche-Lazcano,

Dunkley,

Scarborough

et al. 2023

Preprint

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“…HIV-1 infection modifies the miRNA profile in plasma [65,80], peripheral blood mononuclear cells [81], and gastrointestinal mucosa [82]. These altered miRNA profiles can potentially serve as efficient biomarkers for HIV-1 diagnosis and disease progression [83].…”

Section: Micrornas As Biomarkers Of Liver Disease Progression In Hiv-...mentioning

confidence: 99%

Circulating MicroRNAs as a Tool for Diagnosis of Liver Disease Progression in People Living with HIV-1

Martı́nez

Tural

Franco

2022

Viruses

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MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding specific cell mRNA targets, preventing their translation. miRNAs are implicated in the regulation of important physiological and pathological pathways. Liver disease, including injury, fibrosis, metabolism dysregulation, and tumor development disrupts liver-associated miRNAs. In addition to their effect in the originating tissue, miRNAs can also circulate in body fluids. miRNA release is an important form of intercellular communication that plays a role in the physiological and pathological processes underlying multiple diseases. Circulating plasma levels of miRNAs have been identified as potential disease biomarkers. One of the main challenges clinics face is the lack of available noninvasive biomarkers for diagnosing and predicting the different stages of liver disease (e.g., nonalcoholic fatty liver disease and nonalcoholic steatohepatitis), particularly among individuals infected with human immunodeficiency virus type 1 (HIV-1). Liver disease is a leading cause of death unrelated to acquired immunodeficiency syndrome (AIDS) among people living with HIV-1 (PLWH). Here, we review and discuss the utility of circulating miRNAs as biomarkers for early diagnosis, prognosis, and assessment of liver disease in PLWH. Remarkably, the identification of dysregulated miRNA expression may also identify targets for new therapeutics.

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“…In their manuscript in this issue of AIDS , Fulcher et al identify a potentially novel target for interventions to reduce mucosal inflammation in HIV infection, and by extension, microbial translocation [6]. MicroRNAs (miRs) are a recently described subset of nucleic acids that perform a variety of signaling activities both within and between cells and several have been shown to exert immunologic effects.…”

mentioning

confidence: 99%