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MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNA-seq profiling of miRNAs and mRNAs expressed in CD4+ T lymphocytes upon HIV-1 infection. Our results reveal significant alterations in miRNA and mRNA expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T cells. The addition of miRNA-26a mimics to CD4+ T cells reduces CD59 at both the mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking out CD59 in CD4+ T cells renders both HIV-1-infected cells and progeny virions more prone to antibody-dependent CML (ADCML). The addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction in CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation. [ABSTRACT FROM AUTHOR]

The greenstone belts along the northern margin of the Wawa subprovince of the Superior Province (Vermilion, Shebandowan, Winston Lake, Manitouwadge) formed at ca. 2720 Ma and have been interpreted to be representative of a rifted-arc to back-arc tectonic setting. Despite a common inferred tectonic setting and broad similarities, these greenstone belts have a significantly different metallogeny as evidenced by different endowments in volcanogenic massive sulphide (VMS), magmatic sulphide, and orogenic gold deposits. In this paper, we examine differences in geodynamic setting and crustal architecture as they pertain to the metallogeny of each greenstone belt by characterizing the regional-scale trace-element and isotopic (Nd and Pb) geochemistry of each belt. The trace-element geochemistry of the Vermilion greenstone belt (VGB) shows evidence for a transition from arc-like to back-arc mafic rocks in the Soudan belt to plume-driven rifted arcs in the ultramafic-bearing Newton belt. The Shebandowan greenstone belt (SGB) has a significant proportion of calc-alkalic, arc-like basalts, intermediate lithofacies, and high-Mg andesites, which are characteristic of low-angle, 'hot' subduction. Extensional settings within the SGB are plume-driven and associated with komatiitic ultramafic and mid-ocean ridge basalt (MORB)-like basalts. The Winston Lake greenstone belt (WGB) is characterized by a transition from calc-alkalic, arc-like basalts to back-arc basalts upward in the strata and is capped by alkalic ocean-island basalt (OIB)-like basalts. This association is consistent with plume-driven rifting of a mature arc setting. Each of the VGB, SGB, and WGB show some isotopic evidence for the interaction with a juvenile or slightly older differentiated crust. The Manitouwadge greenstone belt (MGB) is characterized by isotopically juvenile, bimodal, tholeiitic to transitional volcanic lithofacies in a back-arc setting. The MGB is the most isotopically juvenile belt and is also the most productive in terms of VMS mineralization. The Zn-rich VMS mineralization within the WGB suggests a relatively lower-temperature hydrothermal system, possibly within a relatively shallow-water environment. The Zn-dominated and locally Au-enriched VMS mineralization, as well as mafic lithofacies and alteration assemblages, are characteristic of relatively shallower-water deposition in the VGB and SGB, and indicate that the ideal VMS-forming tectonic condition may have been compromised by a shallower-water depositional setting. However, the thickened arc crust and compressional tectonics of the SGB suprasubduction zone during hot subduction may have provided a crustal setting more favourable for the magmatic NiCu sulphide and relative gold endowment of this belt. Les ceintures de roches vertes le long de la bordure nord de la sous-province de Wawa de la Province du Superieur (Vermilion, Shebandowan, Winston Lake, Manitouwadge) ont ete formees il y a environ 2720 Ma et elles ont ete interpretees comme representant un environnement tectonique d'arc distendu a arriere-arc. Malgre un environnement tectonique commun infere et de grandes similarites, ces ceintures de roches vertes ont des metallogenies tres differentes, tel que mis en evidence par differents enrichissements dans les gisements de sulfures massifs volcanogenes (SMV), de sulfures magmatiques et d'or orogenique. Dans le present article, nous examinons les differences dans les environnements geodynamiques et l'architecture de la croute, soit la maniere dont ces differences concernent la metallogenie de chaque ceinture de roches vertes, en caracterisant les elements traces, a l'echelle regionale, et la geochimie des isotopes (Nd et Pb) de chaque ceinture. La geochimie des elements traces de la ceinture de roches vertes Vermillon (VGB) montre des evidences d'une transition de roches mafiques de style arc a arriere-arc dans la ceinture Soudan, a des arcs distendus par des panaches dans la ceinture de roches ultramafiques de Newton. La ceinture de roches vertes Shebandowan (SGB) contient une proportion significative de basaltes calco-alcalins de type arc, de lithofacies intermediaires et d'andesites a forte teneur en Mg, lesquels sont caracteristiques d'une subduction << chaude >> a angle faible. Les environnements d'extension dans la SGB sont entraines par un panache et ils sont associes a des basaltes ultramafiques komatiitiques et de type dorsale mediooceanique (MORB). La ceinture de roches vertes de Winston Lake (WGB) est caracterisee par une transition de basaltes calco-alcalins de type arc a des basaltes d'arriere-arc vers le haut des strates; elle est coiffee de basaltes alcalin de type basalte d'iles oceaniques (OIB). Cette association concorde avec la distension d'un environnement d'arc mature par un panache. Chacune des ceintures VGB, SGB et WGB montre une certaine evidence pour une interaction avec une croute differenciee juvenile ou legerement plus agee. La ceinture de roches vertes Manitouwadge (MGB) est caracterisee par des lithofacies volcaniques a jeunes isotopes, bimodales, tholeiitiques a transitionnels dans un environnement d'arriere-arc. La MGB comporte les isotopes les plus jeunes et elle est aussi la plus productive en termes de mineralisation en SMV. La mineralisation en SMV riches en zinc dans la WGB suggere un systeme hydrothermal a temperature relativement basse, possiblement dans un environnement d'eau relativement peu profonde. La mineralisation en SMV, dominee par Zn et par endroits enrichie en Au ainsi que les lithofacies mafiques et les assemblages d'alteration sont caracteristiques d'une deposition en eau relativement moins profonde dans la VGB et la SGB; cela indique que la condition tectonique de formation ideale pour la SMV pourrait avoir ete compromise par une deposition dans un environnement aquatique moins profond. Toutefois, l'arc crustal epaissi et la tectonique de compression de la zone de suprasubduction de la SGB durant la subduction chaude pourraient avoir fourni un environnement crustal plus favorable pour l'enrichissement magmatique en sulfures de Ni-Cu et relatif d'or de cette ceinture. [Traduit par la Redaction], Introduction The Wawa subprovince is part of the Wawa-Abitibi terrane, which is the youngest accreted granite-greenstone terrane of the Superior Province (Stott 2011). The Neoarchean greenstone belts of the Wawa [...]

Agonist-induced endocytosis and processing of the G protein-coupled A[T.sub.1] angiotensin II (Ang II) receptor (A[T.sub.1] R) was studied in HEK 293 cells expressing green fluorescent protein (GFP)--or hemagglutinin epitope--tagged forms of the receptor. After stimulation with Ang II, the receptor and its ligand colocalized with Rab5-GFP and Rab4--GFP in early endosomes, and subsequently with Rab11--GFP in pericentriolar recycling endosomes. Inhibition of phosphatidylinositol (PI) 3-kinase by wortmannin (WT) or LY294002 caused the formation of large endosomal vesicles of heterogeneous Rab composition, containing the ligand-receptor complex in their limiting membranes and in small associated vesicular structures. In contrast to Alexa[R]-transferrin, which was mainly found in small vesicles associated with the outside of large vesicles in WT-treated cells, rhodamine--Ang II was also segregated into small internal vesicles. In cells labeled with [sup.125]I-Ang II, WT treatment did not impair the rate of receptor endocytosis, but significantly reduced the initial phase of receptor recycling without affecting its slow component. Similarly, WT inhibited the early, but not the slow, component of the recovery of A[T.sub.1]R at the cell surface after termination of Ang II stimulation. These data indicate that internalized A[T.sub.1] receptors are processed via vesicles that resemble multivesicular bodies, and recycle to the cell surface by a rapid PI 3-kinase--dependent recycling route, as well as by a slower pathway that is less sensitive to PI 3-kinase inhibitors.

Antiretroviral therapy (ART) inhibits HIV-1 replication and disease progression but does not lead to a cure. During ART, the integrated HIV-1 genome persists mainly in memory CD4+ T lymphocytes, as well as in other immune cells, such as macrophages. Most of these cells do not produce viral particles, establishing a latent reservoir. Much progress has been made in identifying factors that contribute to the establishment and maintenance of latent reservoirs; however, they remain the main hurdle for HIV-1 eradication. In this review, we discuss the role of microRNAs in the development of the viral reservoir. These modulators of gene expression target effectors governing productive infection and have even direct impacts on viral transcripts. In this review, we consider current unresolved questions regarding host microRNAs in HIV-1 persistence, particularly those involved in viral latency. Additionally, given that current strategies have yet to effectively reduce viral reservoirs, the potential use of microRNAs to counter the persistence of latent reservoirs is also discussed. [ABSTRACT FROM AUTHOR]