@article{Chavanas2016,

title = {Peroxisome proliferator-activated receptor γ (PPARγ) activation: A key determinant of neuropathogeny during congenital infection by cytomegalovirus},

author = {Stéphane Chavanas},

doi = {10.1080/23262133.2016.1231654},

issn = {2326-2133},

year  = {2016},

date = {2016-01-00},

urldate = {2016-01-00},

journal = {Neurogenesis},

volume = {3},

number = {1},

publisher = {Informa UK Limited},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Suberbielle2015,

title = {DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice},

author = {Elsa Suberbielle and Biljana Djukic and Mark Evans and Daniel H. Kim and Praveen Taneja and Xin Wang and Mariel Finucane and Joseph Knox and Kaitlyn Ho and Nino Devidze and Eliezer Masliah and Lennart Mucke},

doi = {10.1038/ncomms9897},

issn = {2041-1723},

year  = {2015},

date = {2015-12-22},

urldate = {2015-12-22},

journal = {Nat Commun},

volume = {6},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer’s disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice. Amyloid-β oligomers reduced BRCA1 levels in primary neuronal cultures. In wild-type mice, knocking down neuronal BRCA1 in the dentate gyrus caused increased DNA double-strand breaks, neuronal shrinkage, synaptic plasticity impairments, and learning and memory deficits, but not apoptosis. Low levels of hAPP/Amyloid-β overexpression exacerbated these effects. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic <jats:italic>N</jats:italic>-methyl-<jats:sc>D</jats:sc>-aspartate receptors promoted the proteasomal degradation of BRCA1. We conclude that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valentin2015,

title = {Increased expression of caspase-1 and interleukin-18 in peeling skin disease, and a novel mutation of corneodesmosin.},

author = {Valentin, Frederic and Oji, Vinzenz and Hausser, Ingrid and Liebau, Eva and Tarinski, Tatjana and Metze, Dieter and Breitkreutz, Dirk and Traupe, Heiko and Jonca, Nathalie and Terheyden, Patrick},

doi = {10.2340/00015555-2142},

issn = {1651-2057 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Acta dermato-venereologica},

volume = {95},

number = {8},

pages = {1019--1021},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{LeLamer2015,

title = {Defects of corneocyte structural proteins and epidermal barrier in atopic dermatitis.},

author = {Le Lamer, Marina and Pellerin, Laurence and Reynier, Marie and Cau, Laura and Pendaries, Valérie and Leprince, Corinne and Méchin, Marie-Claire and Serre, Guy and Paul, Carle and Simon, Michel},

doi = {10.1515/hsz-2015-0141},

issn = {1437-4315 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {Biological chemistry},

volume = {396},

number = {11},

pages = {1163--1179},

abstract = {The main function of the epidermis is to establish a vital multifunctional barrier between the body and its external environment. A defective epidermal barrier is one of the key features of atopic dermatitis (AD), a chronic and relapsing inflammatory skin disorder that affects up to 20% of children and 2-3% of adults and often precedes the development of allergic rhinitis and asthma. This review summarizes recent discoveries on the origin of the skin barrier alterations in AD at the structural protein level, including hereditary and acquired components. The consequences of the epidermal barrier alteration on our current understanding of the pathogenesis of AD, and its possible implications on the treatment of patients, are discussed here.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Viret2015,

title = {The T Cell Repertoire-Diversifying Enzyme TSSP Contributes to Thymic Selection of Diabetogenic CD4 T Cell Specificities Reactive to ChgA and IAPP Autoantigens},

author = {Viret, C. and Mahiddine, K. and Baker, R.L. and Haskins, K. and Guerder, S },

url = {https://www.ncbi.nlm.nih.gov/pubmed/26209627},

doi = {10.4049/jimmunol.1401683},

year  = {2015},

date = {2015-09-01},

journal = {J Immunol },

volume = {5},

number = {195},

pages = {1964-1973},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lefebvre_lc-msms_2015,

title = {LC-MS/MS method for hepcidin-25 measurement in human and mouse serum: clinical and research implications in iron disorders},

author = {Lefebvre, Thibaud and Dessendier, Nathalie and Houamel, Dounia and Ialy-Radio, Nathalie and Kannengiesser, Caroline and Manceau, Hana and Beaumont, Carole and Nicolas, Gael and Gouya, Laurent and Puy, Hervé and Karim, Zoubida},

doi = {10.1515/cclm-2014-1093},

issn = {1437-4331},

year  = {2015},

date = {2015-09-01},

journal = {Clinical Chemistry and Laboratory Medicine},

volume = {53},

number = {10},

pages = {1557--1567},

abstract = {BACKGROUND: The peptide hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. This 25-amino acid hormone is produced and secreted predominantly by hepatocytes. Hepcidin has been suggested as a promising diagnostic marker for iron-related disorders. However, its accurate quantification for clinical use remains so far challenging. In this report we describe a highly specific and quantitative serum hepcidin method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). 

MATERIAL: The analytical validation included the determination of the limit of detection, of quantification, repeatability, reproducibility and linearity. This assay was developed for human and mouse hepcidin. The human assay was performed on serum patients with unexplained microcytic anemia. We applied our LC-MS/MS method for quantifying hepcidin-1 in mouse in various conditions: inflammation, hemolytic anemia, Hamp-1, Hjv and Hfe KO mice. RESULTS: We show that the LC-MS/MS is suitable for accurate determination of hepcidin-25 in clinical samples, thereby representing a useful tool for the clinical diagnosis and follow-up of iron-related diseases. In mouse, a strong correlation between hepatic Hamp-1 mRNA expression and serum hepcidin-1 levels was found (r=0.88; p=0.0002) and the expected variations in mouse models of iron disorders were observed. 

CONCLUSIONS: Therefore, we propose this adaptive LC-MS/MS method as a suitable method for accurate determination of hepcidin-25 in clinical samples and as a major tool contributing to the clinical diagnosis, follow-up and management of iron-related disorders. It also opens new avenues to measure hepcidin in animal models without interspecies antigenic limitations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{karim_porphyrias_2015,

title = {Porphyrias: A 2015 update},

author = {Karim, Zoubida and Lyoumi, Said and Nicolas, Gael and Deybach, Jean-Charles and Gouya, Laurent and Puy, Hervé},

doi = {10.1016/j.clinre.2015.05.009},

issn = {2210-741X},

year  = {2015},

date = {2015-09-01},

journal = {Clinics and Research in Hepatology and Gastroenterology},

volume = {39},

number = {4},

pages = {412--425},

abstract = {The hereditary porphyrias comprise a group of eight metabolic disorders of the heme biosynthesis pathway. Each porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of heme precursors. Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which heme precursors (δ-aminolevulinic acid [ALA], porphobilinogen and porphyrins) are overproduced. Clinically, porphyrias are characterized by acute neurovisceral symptoms, skin lesions or both. However, most if not all the porphyrias impair hepatic or gastrointestinal function. Acute hepatic porphyrias present with severe abdominal pain, nausea, constipation, confusion and seizure, which may be life threatening, and patients are at risk of hepatocellular carcinoma without cirrhosis. Porphyria Cutanea presents with skin fragility and blisters, and patients are at risk of hepatocellular carcinoma with liver iron overload. Erythropoietic protoporphyria and X-linked protoporphyria present with acute painful photosensitivity, and patients are at risk of acute liver failure. Altogether, porphyrias are still underdiagnosed, but once they are suspected, early diagnosis based on measurement of biochemical metabolites that accumulate in the blood, urine, or feces is essential so specific treatment can be started as soon as possible and long-term liver complications are prevented. Screening families to identify presymptomatic carriers is also crucial to prevent overt disease and chronic hepatic complications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{homedan_mitochondrial_2015,

title = {Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria},

author = {Homedan, Chadi and Schmitt, Caroline and Laafi, Jihane and Gueguen, Naïg and Desquiret-Dumas, Valérie and Lenglet, Hugo and Karim, Zoubida and Gouya, Laurent and Deybach, Jean-Charles and Simard, Gilles and Puy, Hervé and Malthièry, Yves and Reynier, Pascal},

doi = {10.1093/hmg/ddv222},

issn = {1460-2083},

year  = {2015},

date = {2015-09-01},

journal = {Human Molecular Genetics},

volume = {24},

number = {17},

pages = {5015--5023},

abstract = {Acute intermittent porphyria (AIP), an autosomal dominant metabolic disease (MIM #176000), is due to a deficiency of hydroxymethylbilane synthase (HMBS), which catalyzes the third step of the heme biosynthetic pathway. The clinical expression of the disease is mainly neurological, involving the autonomous, central and peripheral nervous systems. We explored mitochondrial oxidative phosphorylation (OXPHOS) in the brain and skeletal muscle of the Hmbs(-/-) mouse model first in the basal state (BS), and then after induction of the disease with phenobarbital and treatment with heme arginate (HA). The modification of the respiratory parameters, determined in mice in the BS, reflected a spontaneous metabolic energetic adaptation to HMBS deficiency. Phenobarbital induced a sharp alteration of the oxidative metabolism with a significant decrease of ATP production in skeletal muscle that was restored by treatment with HA. This OXPHOS defect was due to deficiencies in complexes I and II in the skeletal muscle whereas all four respiratory chain complexes were affected in the brain. To date, the pathogenesis of AIP has been mainly attributed to the neurotoxicity of aminolevulinic acid and heme deficiency. Our results show that mitochondrial energetic failure also plays an important role in the expression of the disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pallet_high_2015,

title = {High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria},

author = {Pallet, Nicolas and Mami, Iadh and Schmitt, Caroline and Karim, Zoubida and François, Arnaud and Rabant, Marion and Nochy, Dominique and Gouya, Laurent and Deybach, Jean-Charles and Xu-Dubois, Yichum and Thervet, Eric and Puy, Hervé and Karras, Alexandre},

doi = {10.1038/ki.2015.97},

issn = {1523-1755},

year  = {2015},

date = {2015-08-01},

journal = {Kidney International},

volume = {88},

number = {2},

pages = {386--395},

abstract = {Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of textasciitilde1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leghmar2015,

title = {Cytomegalovirus Infection Triggers the Secretion of the PPARγ Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE) and 13-Hydroxyoctadecadienoic Acid (13-HODE) in Human Cytotrophoblasts and Placental Cultures},

author = {Kaoutar Leghmar and Nicolas Cenac and Maude Rolland and Hélène Martin and Benjamin Rauwel and Justine Bertrand-Michel and Pauline Le Faouder and Mélinda Bénard and Charlotte Casper and Christian Davrinche and Thierry Fournier and Stéphane Chavanas},

editor = {Juliet Spencer},

doi = {10.1371/journal.pone.0132627},

issn = {1932-6203},

year  = {2015},

date = {2015-07-14},

urldate = {2015-07-14},

journal = {PLoS ONE},

volume = {10},

number = {7},

publisher = {Public Library of Science (PLoS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Li2015,

title = {Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells},

author = {Xiao-Jun Li and Xi-Juan Liu and Bo Yang and Ya-Ru Fu and Fei Zhao and Zhang-Zhou Shen and Ling-Feng Miao and Simon Rayner and Stéphane Chavanas and Hua Zhu and William J. Britt and Qiyi Tang and Michael A. McVoy and Min-Hua Luo},

editor = {R. M. Sandri-Goldin},

doi = {10.1128/jvi.00351-15},

issn = {1098-5514},

year  = {2015},

date = {2015-07-00},

urldate = {2015-07-00},

journal = {J Virol},

volume = {89},

number = {13},

pages = {6792--6804},

publisher = {American Society for Microbiology},

abstract = {<jats:title>ABSTRACT</jats:title><jats:p>Human cytomegalovirus (HCMV) infection of the developing fetus frequently results in major neural developmental damage. In previous studies, HCMV was shown to downregulate neural progenitor/stem cell (NPC) markers and induce abnormal differentiation. As Notch signaling plays a vital role in the maintenance of stem cell status and is a switch that governs NPC differentiation, the effect of HCMV infection on the Notch signaling pathway in NPCs was investigated. HCMV downregulated mRNA levels of Notch1 and its ligand, Jag1, and reduced protein levels and altered the intracellular localization of Jag1 and the intracellular effector form of Notch1, NICD1. These effects required HCMV gene expression and appeared to be mediated through enhanced proteasomal degradation. Transient expression of the viral tegument proteins of pp71 and UL26 reduced NICD1 and Jag1 protein levels endogenously and exogenously. Given the critical role of Notch signaling in NPC growth and differentiation, these findings reveal important mechanisms by which HCMV disturbs neural cell development<jats:italic>in vitro</jats:italic>. Similar events<jats:italic>in vivo</jats:italic>may be associated with HCMV-mediated neuropathogenesis during congenital infection in the fetal brain.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>Congenital human cytomegalovirus (HCMV) infection is the leading cause of birth defects that primarily manifest as neurological disabilities. Neural progenitor cells (NPCs), key players in fetal brain development, are the most susceptible cell type for HCMV infection in the fetal brain. Studies have shown that NPCs are fully permissive for HCMV infection, which causes neural cell loss and premature differentiation, thereby perturbing NPC fate. Elucidation of virus-host interactions that govern NPC proliferation and differentiation is critical to understanding neuropathogenesis. The Notch signaling pathway is critical for maintaining stem cell status and functions as a switch for differentiation of NPCs. Our investigation into the impact of HCMV infection on this pathway revealed that HCMV dysregulates Notch signaling by altering expression of the Notch ligand Jag1, Notch1, and its active effector in NPCs. These results suggest a mechanism for the neuropathogenesis induced by HCMV infection that includes altered NPC differentiation and proliferation.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bonnaud2015,

title = {Borna Disease Virus Phosphoprotein Modulates Epigenetic Signaling in Neurons To Control Viral Replication},

author = {Emilie M. Bonnaud and Marion Szelechowski and Alexandre Bétourné and Charlotte Foret and Anne Thouard and Daniel Gonzalez-Dunia and Cécile E. Malnou},

editor = {S. R. Ross},

doi = {10.1128/jvi.00454-15},

issn = {1098-5514},

year  = {2015},

date = {2015-06-00},

urldate = {2015-06-00},

journal = {J Virol},

volume = {89},

number = {11},

pages = {5996--6008},

publisher = {American Society for Microbiology},

abstract = {<jats:title>ABSTRACT</jats:title>

          <jats:p>Understanding the modalities of interaction of neurotropic viruses with their target cells represents a major challenge that may improve our knowledge of many human neurological disorders for which viral origin is suspected. Borna disease virus (BDV) represents an ideal model to analyze the molecular mechanisms of viral persistence in neurons and its consequences for neuronal homeostasis. It is now established that BDV ensures its long-term maintenance in infected cells through a stable interaction of viral components with the host cell chromatin, in particular, with core histones. This has led to our hypothesis that such an interaction may trigger epigenetic changes in the host cell. Here, we focused on histone acetylation, which plays key roles in epigenetic regulation of gene expression, notably for neurons. We performed a comparative analysis of histone acetylation patterns of neurons infected or not infected by BDV, which revealed that infection decreases histone acetylation on selected lysine residues. We showed that the BDV phosphoprotein (P) is responsible for these perturbations, even when it is expressed alone independently of the viral context, and that this action depends on its phosphorylation by protein kinase C. We also demonstrated that BDV P inhibits cellular histone acetyltransferase activities. Finally, by pharmacologically manipulating cellular acetylation levels, we observed that inhibiting cellular acetyl transferases reduces viral replication in cell culture. Our findings reveal that manipulation of cellular epigenetics by BDV could be a means to modulate viral replication and thus illustrate a fascinating example of virus-host cell interaction.</jats:p>

          <jats:p>

            <jats:bold>IMPORTANCE</jats:bold>

            Persistent DNA viruses often subvert the mechanisms that regulate cellular chromatin dynamics, thereby benefitting from the resulting epigenetic changes to create a favorable milieu for their latent and persistent states. Here, we reasoned that Borna disease virus (BDV), the only RNA virus known to durably persist in the nucleus of infected cells, notably neurons, might employ a similar mechanism. In this study, we uncovered a novel modality of virus-cell interaction in which BDV phosphoprotein inhibits cellular histone acetylation by interfering with histone acetyltransferase activities. Manipulation of cellular histone acetylation is accompanied by a modulation of viral replication, revealing a perfect adaptation of this “ancient” virus to its host that may favor neuronal persistence and limit cellular damage.

          </jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scordel2015b,

title = {Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis},

author = {Chloé Scordel and Alexandra Huttin and Marielle Cochet-Bernoin and Marion Szelechowski and Aurélie Poulet and Jennifer Richardson and Alexandra Benchoua and Daniel Gonzalez-Dunia and Marc Eloit and Muriel Coulpier},

editor = {Martin Schwemmle},

doi = {10.1371/journal.ppat.1004859},

issn = {1553-7374},

year  = {2015},

date = {2015-04-29},

journal = {PLoS Pathog},

volume = {11},

number = {4},

publisher = {Public Library of Science (PLoS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pendaries2015,

title = {In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification.},

author = {Pendaries, V and Le Lamer, M and Cau, L and Hansmann, B and Malaisse, J and Kezic, S and Serre, G and Simon, M},

doi = {10.1038/cddis.2015.29},

issn = {2041-4889 (Electronic)},

year  = {2015},

date = {2015-02-01},

journal = {Cell death & disease},

volume = {6},

number = {2},

pages = {e1656},

abstract = {Atopic dermatitis is a chronic inflammatory skin disease with defects in the epidermal barrier. In a cohort of African-American children, a FLG2 nonsense mutation has been associated with the disease. In the epidermis of European patients, the expression of filaggrin-2, the filaggrin-related protein encoded by FLG2, is decreased. To describe the function of filaggrin-2 and evaluate the impact of its deficiency, its expression was downregulated using lentivirus-mediated shRNA interference in a three-dimensional reconstructed human epidermis (RHE) model. This resulted in parakeratosis and a compact stratum corneum, presence of abnormal vesicles inside the corneocytes, increased pH and reduced amounts of free amino acids at the RHE surface, leading to increased sensitivity to UVB radiations. The expression of differentiation markers was slightly modified. However, we observed reduced proteolytic processing of corneodesmosin, hornerin and filaggrin in parallel with reduced amounts of caspase-14 and bleomycin hydrolase. Our data demonstrated that filaggrin-2 is important for a proper cornification and a functional stratum corneum. Its downregulation in atopic patients may be involved in the disease-associated epidermis impairment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{martelli_iron_2015,

title = {Iron regulatory protein 1 sustains mitochondrial iron loading and function in frataxin deficiency},

author = {Martelli, Alain and Schmucker, Stéphane and Reutenauer, Laurence and Mathieu, Jacques R. R. and Peyssonnaux, Carole and Karim, Zoubida and Puy, Hervé and Galy, Bruno and Hentze, Matthias W. and Puccio, Hélène},

doi = {10.1016/j.cmet.2015.01.010},

issn = {1932-7420},

year  = {2015},

date = {2015-02-01},

journal = {Cell Metabolism},

volume = {21},

number = {2},

pages = {311--323},

abstract = {Mitochondrial iron accumulation is a hallmark of diseases associated with impaired iron-sulfur cluster (Fe-S) biogenesis, such as Friedreich ataxia linked to frataxin (FXN) deficiency. The pathophysiological relevance of the mitochondrial iron loading and the underlying mechanisms are unknown. Using a mouse model of hepatic FXN deficiency in combination with mice deficient for iron regulatory protein 1 (IRP1), a key regulator of cellular iron metabolism, we show that IRP1 activation in conditions of Fe-S deficiency increases the available cytosolic labile iron pool. Surprisingly, our data indicate that IRP1 activation sustains mitochondrial iron supply and function rather than driving detrimental iron overload. Mitochondrial iron accumulation is shown to depend on mitochondrial dysfunction and heme-dependent upregulation of the mitochondrial iron importer mitoferrin-2. Our results uncover an unexpected protective role of IRP1 in pathological conditions associated with altered Fe-S metabolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fu2015,

title = {MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a},

author = {Ya-Ru Fu and Xi-Juan Liu and Xiao-Jun Li and Zhang-zhou Shen and Bo Yang and Cong-Cong Wu and Jia-Fu Li and Ling-Feng Miao and Han-Qing Ye and Guan-Hua Qiao and Simon Rayner and Stéphane Chavanas and Christian Davrinche and William J. Britt and Qiyi Tang and Michael McVoy and Edward Mocarski and Min-Hua Luo},

editor = {R. M. Sandri-Goldin},

doi = {10.1128/jvi.01740-14},

issn = {1098-5514},

year  = {2015},

date = {2015-01-15},

urldate = {2015-01-15},

journal = {J Virol},

volume = {89},

number = {2},

pages = {1070--1082},

publisher = {American Society for Microbiology},

abstract = {<jats:title>ABSTRACT</jats:title><jats:p>Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in turn modifies the cellular environment to favor virus replication. Previous observations found that HCMV infection reduces miR-21 expression in neural progenitor/stem cells (NPCs). Here, we show that infection of NPCs and U-251MG cells represses miR-21 while increasing the levels of Cdc25a, a cell cycle regulator and known target of miR-21. These opposing responses to infection prompted an investigation of the relationship between miR-21, Cdc25a, and viral replication. Overexpression of miR-21 in NPCs and U-251MG cells inhibited viral gene expression, genome replication, and production of infectious progeny, while shRNA-knockdown of miR-21 in U-251MG cells increased viral gene expression. In contrast, overexpression of Cdc25a in U-251MG cells increased viral gene expression and production of infectious progeny and overcame the inhibitory effects of miR-21 overexpression. Three viral gene products—IE1, pp71, and UL26—were shown to inhibit miR-21 expression at the transcriptional level. These results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a levels after HCMV infection are due in part to HCMV-mediated repression of miR-21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV infection. This suggests a role for miR-21 downregulation in the neuropathogenesis of HCMV infection of the developing CNS.</jats:p><jats:p><jats:bold>IMPORTANCE</jats:bold>Human cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence among population, especially in China, and congenital HCMV infection is a major cause for birth defects. Elucidating virus-host interactions that govern HCMV replication in neuronal cells is critical to understanding the neuropathogenesis of birth defects resulting from congenital infection. In this study, we confirm that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further determined the negative effects of cellular miRNA miR-21 on HCMV replication in neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More importantly, our results provide the first evidence that miR-21 negatively regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We further found that viral gene products of IE1, pp71, and UL26 play roles in inhibiting miR-21 expression, which in turn causes increases in Cdc25a and benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral factor that represents a potential target for therapeutic intervention.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN4b,

title = {A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity},

author = {Garcia-Perez, J. and Staropoli, I. and Azoulay, S. and Heinrich, J. T. and Cascajero, A. and Colin, P. and Lortat-Jacob, H. and Arenzana-Seisdedos, F. and Alcami, J. and Kellenberger, E. and Lagane, B.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26081316},

doi = {10.1186/s12977-015-0177-1},

issn = {1742-4690 (Electronic) 

1742-4690 (Linking)},

year  = {2015},

date = {2015-01-01},

journal = {Retrovirology},

volume = {12},

pages = {50},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1b,

title = {Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism},

author = {Jeanne, N. and Saliou, A. and Carcenac, R. and Lefebvre, C. and Dubois, M. and Cazabat, M. and Nicot, F. and Loiseau, C. and Raymond, S. and Izopet, J. and Delobel, P.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26585833},

doi = {10.1038/srep16944},

issn = {2045-2322 (Electronic) 

2045-2322 (Linking)},

year  = {2015},

date = {2015-01-01},

journal = {Sci Rep},

volume = {5},

pages = {16944},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN10,

title = {Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy},

author = {Lhomme, S. and Kamar, N. and Nicot, F. and Ducos, J. and Bismuth, M. and Garrigue, V. and Petitjean-Lecherbonnier, J. and Ollivier, I. and Alessandri-Gradt, E. and Goria, O. and Barth, H. and Perrin, P. and Saune, K. and Dubois, M. and Carcenac, R. and Lefebvre, C. and Jeanne, N. and Abravanel, F. and Izopet, J.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26711757},

doi = {10.1128/AAC.02496-15},

issn = {1098-6596 (Electronic) 

0066-4804 (Linking)},

year  = {2015},

date = {2015-01-01},

journal = {Antimicrob Agents Chemother},

volume = {60},

number = {3},

pages = {1608-14},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN26,

title = {Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi Syndrome},

author = {Bieth, E. and Eddiry, S. and Gaston, V. and Lorenzini, F. and Buffet, A. and Conte Auriol, F. and Molinas, C. and Cailley, D. and Rooryck, C. and Arveiler, B. and Cavaille, J. and Salles, J. P. and Tauber, M.},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24916642},

doi = {10.1038/ejhg.2014.103},

issn = {1476-5438 (Electronic) 

1018-4813 (Linking)},

year  = {2015},

date = {2015-01-01},

journal = {Eur J Hum Genet},

volume = {23},

number = {2},

pages = {252-5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}