HIV-l and the microRNA-guided silencing pathway: An intricate and multifaceted encounter

Provost, Patrick; Barat, Corinne; Plante, Isabelle; Tremblay, Michel J.

doi:10.1016/j.virusres.2006.06.015

Cited by 14 publications

(12 citation statements)

References 77 publications

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“…Interestingly, there has been some past debate as to whether or not HIV-1 produces miRNAs of its own, so-called viral miRNAs (27). Recent evidence supports the idea that HIV-1 encodes multiple conserved RNA stem-loop structures that can act as a source of viral miRNAs (28). The earliest direct evidence of viral miRNA was found by Northern blot analysis (14,29).…”

mentioning

confidence: 99%

Absence of DICER in Monocytes and Its Regulation by HIV-1

Coley

Duyne

Carpio

et al. 2010

Journal of Biological Chemistry

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MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's miRNA pathway for its own benefit. In this study, we examined the state of miRNA production in monocytes and macrophages as well as the consequences of viral infection upon the production of miRNA. Monocytes in general express low amounts of miRNA-related proteins, and DICER in particular could not be detected until after monocytes were differentiated into macrophages. In the case where HIV-1 was present prior to differentiation, the expression of DICER was suppressed. MicroRNA chip results for RNA isolated from transfected and treated cells indicated that a drop in miRNA production coincided with DICER protein suppression in macrophages. We found that the expression of DICER in monocytes is restricted by miR-106a, but HIV-1 suppressed DICER expression via the viral gene Vpr. Additionally, analysis of miRNA expression in monocytes and macrophages revealed evidence that some miRNAs can be processed by both DICER and PIWIL4. Results presented here have implications for both the pathology of viral infections in macrophages and the biogenesis of miRNAs. First, HIV-1 suppresses the expression and function of DICER in macrophages via a previously unknown mechanism. Second, the presence of miRNAs in monocytes lacking DICER indicates that some miRNAs can be generated by proteins other than DICER. Human immunodeficiency virus, type 1 (HIV-1) infects multiple types of cells, including CD4ϩ T-cells, macrophages, monocytes, dendritic cells, and microglial cells (1-5). It has also been reported that latently infected hematopoietic stem cells can be detected in HIV-1-positive patients (6, 7). However, despite the range of susceptible cell types, HIV-1 is typically discussed in the context of T-cell infection and the resulting depletion of CD4 ϩ T-cells. Conversely, research into HIV-1 infection in the context of monocytes and macrophages remains underdeveloped. Monocytes and macrophages have been previously shown to harbor both productive and latent infections, serving as a part of the viral reservoir that could potentially be essential to chronic infection (8, 9). Unlike T-cells, macrophages can resist the cytotoxic effects of HIV-1 infection and persist for several months while producing new infectious viral particles (10 -12). In fact, it has been observed that latently infected macrophages are responsible for a large amount of viral resurgence after cessation of anti-retroviral therapies (13). Interestingly, we have previously observed that monocytes differ greatly from T-cells in their expression of miRNA-related enzymes. Specifically, monocytes appeared to be deficient for the DICER enzyme (14). This observation was intriguing because previous reports have indicated that HIV-1 can manipulate the host's RNA inter...

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confidence: 99%

Absence of DICER in Monocytes and Its Regulation by HIV-1

Coley

Duyne

Carpio

et al. 2010

Journal of Biological Chemistry

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“…The importance of miRNAs in HIV-1 infection, particularly in interpreting the replication restriction of HIV-1 in primary monocytes and resting primary CD4 ϩ T lymphocytes, has been well established (22)(23)(24)(25)(26)(27)(28)(29). miRNAs, such as miR-21 (30), miR-146a (31), and miR-155 (32), are important regulators in the TLR4 pathway and exert their influence by targeting multiple sites in the signaling cascade, but little is known about the role of miRNAs in regulating the immune response during chronic HIV-1 infection in monocytes, an important source of inflammatory cytokines.…”

Section: Abstract Cyld Hiv-1 Inflammatory Responses Mir-126-5p Momentioning

confidence: 99%

MicroRNA miR-126-5p Enhances the Inflammatory Responses of Monocytes to Lipopolysaccharide Stimulation by Suppressing Cylindromatosis in Chronic HIV-1 Infection

Huang

Zhu

Qiu

et al. 2017

J Virol

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Persistent immune activation during chronic human immunodeficiency virus type 1 (HIV-1) infection facilitates immune dysfunction and thereby fuels disease progression. The translocation of bacterial derivatives into blood and the hyperinflammatory responsiveness of monocytes have been considered important causative factors for persistent immune activation. Whether microRNAs (miRNAs) are involved in regulating monocyte-mediated inflammatory responses during chronic HIV-1 infection remains elusive. In this study, we show that miR-126-5p functions as a positive regulator of monocyte-mediated inflammatory responses. Significantly increased miRNA miR-126-5p and decreased cylindromatosis (CYLD) were observed in primary monocytes from chronic HIV-1 patients. Inhibition of miR-126-5p in monocytes from chronic HIV-1 patients attenuated the responsiveness of these cells to lipopolysaccharide (LPS) stimulation. Gain-of-function assays confirmed that miR-126-5p could downregulate CYLD, which in turn caused an upregulation of phosphorylation of JNK protein (pJNK) and enhanced inflammatory responses of monocytes to LPS stimulation. Overall, miR-126-5p upregulates the responsiveness of monocytes to LPS stimulation in chronic HIV-1 infection, and the suppression of miR-126-5p and the promotion of CYLD expression in primary monocytes may represent a practical immune intervention strategy to contain persistent inflammation in chronic HIV-1 infection.IMPORTANCE Monocyte-mediated hyperinflammatory responses during chronic HIV-1 infection are important causative factors driving AIDS progression; however, the underlying mechanism has not been fully addressed. We demonstrated that miR-126-5p, one of the most upregulated miRNAs during chronic HIV-1 infection, could enhance the inflammatory responses of monocytes to LPS by suppressing the inhibitory protein CYLD and thereby unleashing the expression of pJNK in the LPS/ Toll-like receptor 4/mitogen-activated protein kinase pathway. This observation reveals a new mechanism for HIV-1 pathogenesis, which could be targeted by immune intervention.

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“…TRBP is also part of a ternary complex comprising Dicer and Ago2 in a sequence of events in which TRBP is required for the recruitment of Ago2 to the siRNA bound by Dicer (21), thereby coupling the initiation step of the miRNA processing and the effector steps of the miRNA pathway. TRBP may thus exert a dual role in HIV-1 pathogenesis and RNA silencing (73), but also in other important physiological processes.…”

Section: Tar Rna Binding Protein and Hiv-1mentioning

confidence: 99%

Protein Components of the microRNA Pathway and Human Diseases

Perron¹,

Provost²

2008

Methods in Molecular Biology

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SummaryMicroRNAs (miRNAs) are key regulators of messenger RNA (mRNA) translation known to be involved in a wide variety of cellular processes. In fact, their individual importance is reflected in the diseases that may arise upon the loss, mutation or dysfunction of specific miRNAs. It has been appreciated only recently that diseases may also develop when the protein components of the miRNA machinery itself are affected. The core enzymes of the major protein complexes involved in miRNA biogenesis and function, such as the ribonucleases III (RNases III) Drosha and Dicer as well as Argonaute 2 (Ago2), appear to be essential. However, the accessory proteins of the miRNA pathway, such as the DiGeorge syndrome critical region gene 8 (DGCR8) protein, Exportin-5 (Exp-5), TAR RNA binding protein (TRBP) and Fragile X mental retardation protein (FMRP), are each related, in various ways, to specific genetic diseases.

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HIV-l and the microRNA-guided silencing pathway: An intricate and multifaceted encounter

Cited by 14 publications

References 77 publications

Absence of DICER in Monocytes and Its Regulation by HIV-1

Absence of DICER in Monocytes and Its Regulation by HIV-1

MicroRNA miR-126-5p Enhances the Inflammatory Responses of Monocytes to Lipopolysaccharide Stimulation by Suppressing Cylindromatosis in Chronic HIV-1 Infection

Protein Components of the microRNA Pathway and Human Diseases

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