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Prof. Nicolas Lévêque
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, LITEC EA 4331, Université de Poitiers, Poitiers, France

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0 Innate Immunity
0 Skin
0 Virus
0 antimicrobial peptides
0 herpes simplex virus

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Virus
Skin
herpes simplex virus
keratinocyte
antimicrobial peptides

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Article
Published: 17 August 2021
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Usutu virus (USUV) and West Nile virus (WNV) are emerging flaviviruses transmitted by mosquitoes. Although they differ in their endemicity, with WNV present throughout much of the world and USUV currently limited to Africa and Europe, both constitute a global public health threat. Since they are directly inoculated in the epidermis and the dermis during mosquito bites, the skin constitutes the initial site of viral replication and immune response. The skin is equipped with a unique network of dendritic cells, which represent an essential outpost of immune defenses. These skin-resident DCs comprise Langerhans cells (LCs) in the epidermis and dermal DCs in the dermis, which capture pathogens through the C-type lectin receptors (CLR) langerin and DC-SIGN, respectively. Despite the key role of these cells in the body’s antiviral defenses, their implication in the immune control and replication of WNV and USUV is not known. Using human skin explants, we show that while both viruses can replicate in keratinocytes, they can also infect resident DCs with distinct tropism, since WNV preferentially infects DCs in the dermis, whereas USUV has a greater propensity to infect LCs. Using both purified human epidermal LCs (eLCs) and monocyte derived LCs (MoLCs), we confirm that LCs sustain a faster and more efficient replication of USUV compared with WNV and that this correlates with a more intense innate immune response to USUV compared with WNV. Next, we show that ectopic expression of langerin in non-permissive cells rendered them permissive to USUV, but not to WNV. Conversely, blocking or silencing langerin in MoLCs or eLCs made them resistant to USUV infection, thus demonstrating that this specific CLR allows USUV to enter and productively infect LCs. Altogether, our results demonstrate that LCs constitute privileged target cells for USUV in human skin, because langerin favors its entry and replication. Intriguingly, this suggests that USUV efficiently escapes the antiviral functions of langerin, which normally safeguards LCs from most viral infections.

ACS Style

Marie-France Martin; Ghizlane Maarifi; Hervé Abiven; Marine Seffals; Nicolas Mouchet; Cécile Beck; Charles Bodet; Nicolas Lévèque; Nathalie J. Arhel; Fabien P. Blanchet; Yannick Simonin; Sébastien Nisole. Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus. 2021, 1 .

AMA Style

Marie-France Martin, Ghizlane Maarifi, Hervé Abiven, Marine Seffals, Nicolas Mouchet, Cécile Beck, Charles Bodet, Nicolas Lévèque, Nathalie J. Arhel, Fabien P. Blanchet, Yannick Simonin, Sébastien Nisole. Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus. . 2021; ():1.

Chicago/Turabian Style

Marie-France Martin; Ghizlane Maarifi; Hervé Abiven; Marine Seffals; Nicolas Mouchet; Cécile Beck; Charles Bodet; Nicolas Lévèque; Nathalie J. Arhel; Fabien P. Blanchet; Yannick Simonin; Sébastien Nisole. 2021. "Usutu virus uses langerin as a receptor to productively infect Langerhans cells more efficiently than West Nile virus." , no. : 1.

Journal article
Published: 24 July 2021 in Pharmaceuticals
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Hg-CATH and Pb-CATH4 are cathelicidins from Heterocephalus glaber and Python bivittatus that have been previously identified as potent antibacterial peptides. However, their antiviral properties were not previously investigated. In this study, their activity against the herpes simplex virus (HSV)-1 was evaluated during primary human keratinocyte infection. Both of them significantly reduced HSV-1 DNA replication and production of infectious viral particles in keratinocytes at noncytotoxic concentrations, with the stronger activity of Pb-CATH4. These peptides did not show direct virucidal activity and did not exhibit significant immunomodulatory properties, except for Pb-CATH4, which exerted a moderate proinflammatory action. All in all, our results suggest that Hg-CATH and Pb-CATH4 could be potent candidates for the development of new therapies against HSV-1.

ACS Style

Alexia Damour; Magali Garcia; Hye-Sun Cho; Andy Larivière; Nicolas Lévêque; Chankyu Park; Charles Bodet. Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1. Pharmaceuticals 2021, 14, 715 .

AMA Style

Alexia Damour, Magali Garcia, Hye-Sun Cho, Andy Larivière, Nicolas Lévêque, Chankyu Park, Charles Bodet. Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1. Pharmaceuticals. 2021; 14 (8):715.

Chicago/Turabian Style

Alexia Damour; Magali Garcia; Hye-Sun Cho; Andy Larivière; Nicolas Lévêque; Chankyu Park; Charles Bodet. 2021. "Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1." Pharmaceuticals 14, no. 8: 715.

Short communication
Published: 15 June 2021 in Current Research in Translational Medicine
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Herpetic encephalitis results from central nervous system invasion by herpes simplex virus. We report the case of a man who developed a cerebral abscess fifteen months after initial Herpetic encephalitis. Retrospectively, antiviral should not have been associated with antibiotics during abscess episode, as transcriptomic analysis reported no viral reactivation.

ACS Style

Mélanie Catroux; Magali Garcia; Nicolas Lévêque; Philippe Page; Gwenael Le Moal; David Boutolleau; France Roblot; Sonia Burrel. Post-herpetic encephalitis cerebral abscess: Viral reactivation or latency site within central nervous system? Current Research in Translational Medicine 2021, 69, 103297 .

AMA Style

Mélanie Catroux, Magali Garcia, Nicolas Lévêque, Philippe Page, Gwenael Le Moal, David Boutolleau, France Roblot, Sonia Burrel. Post-herpetic encephalitis cerebral abscess: Viral reactivation or latency site within central nervous system? Current Research in Translational Medicine. 2021; 69 (3):103297.

Chicago/Turabian Style

Mélanie Catroux; Magali Garcia; Nicolas Lévêque; Philippe Page; Gwenael Le Moal; David Boutolleau; France Roblot; Sonia Burrel. 2021. "Post-herpetic encephalitis cerebral abscess: Viral reactivation or latency site within central nervous system?" Current Research in Translational Medicine 69, no. 3: 103297.

Letter to the editor
Published: 17 May 2021 in Journal of Medical Virology
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ACS Style

Florent Hubert; Céline Chessa; Agnès Beby‐Defaux; Anne Bourgoin; Laurence Boinot; Ursula Noury; Andy Lariviere; Mohammed Benlaassri; Magali Garcia; Nicolas Leveque. Emergence of the SARS‐CoV‐2 B.1.1.7 variant observed at the Poitiers University Hospital. Journal of Medical Virology 2021, 1 .

AMA Style

Florent Hubert, Céline Chessa, Agnès Beby‐Defaux, Anne Bourgoin, Laurence Boinot, Ursula Noury, Andy Lariviere, Mohammed Benlaassri, Magali Garcia, Nicolas Leveque. Emergence of the SARS‐CoV‐2 B.1.1.7 variant observed at the Poitiers University Hospital. Journal of Medical Virology. 2021; ():1.

Chicago/Turabian Style

Florent Hubert; Céline Chessa; Agnès Beby‐Defaux; Anne Bourgoin; Laurence Boinot; Ursula Noury; Andy Lariviere; Mohammed Benlaassri; Magali Garcia; Nicolas Leveque. 2021. "Emergence of the SARS‐CoV‐2 B.1.1.7 variant observed at the Poitiers University Hospital." Journal of Medical Virology , no. : 1.

Review article
Published: 03 June 2020 in Frontiers in Microbiology
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Keratinocytes, the main cells of the epidermis, are the first site of replication as well as the first line of defense against many viruses such as arboviruses, enteroviruses, herpes viruses, human papillomaviruses, or vaccinia virus. During viral replication, these cells can sense virus associated molecular patterns leading to the initiation of an innate immune response composed of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. Human keratinocytes produce and secrete at least nine antimicrobial peptides: human cathelicidin LL-37, types 1–4 human β-defensins, S100 peptides such as psoriasin (S100A7), calprotectin (S100A8/9) and koebnerisin (S100A15), and RNase 7. These peptides can exert direct antiviral effects on the viral particle or its replication cycle, and indirect antiviral activity, by modulating the host immune response. The purpose of this review is to summarize current knowledge of antiviral and immunomodulatory properties of human keratinocyte antimicrobial peptides.

ACS Style

Céline Chessa; Charles Bodet; Clément Jousselin; Michel Wehbe; Nicolas Lévêque; Magali Garcia. Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes. Frontiers in Microbiology 2020, 11, 1155 .

AMA Style

Céline Chessa, Charles Bodet, Clément Jousselin, Michel Wehbe, Nicolas Lévêque, Magali Garcia. Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes. Frontiers in Microbiology. 2020; 11 ():1155.

Chicago/Turabian Style

Céline Chessa; Charles Bodet; Clément Jousselin; Michel Wehbe; Nicolas Lévêque; Magali Garcia. 2020. "Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes." Frontiers in Microbiology 11, no. : 1155.

Communication
Published: 18 January 2019 in Viruses
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Temporins are anti-microbial peptides synthesized in the skin of frogs of the Ranidae family. The few studies to date that have examined their anti-viral properties have shown that they have potential as anti-viral therapies. In this work, we evaluated the anti-herpes simplex virus type 1 (HSV-1) activity of the temporin-SHa (SHa) and its synthetic analog [K3]SHa. Human cathelicidin LL-37 and temporin-Tb (Tb), previously demonstrated to have anti-HSV-1 properties, were used as positive controls. We observed that SHa and [K3]SHa significantly inhibit HSV-1 replication in human primary keratinocytes when used at micromolar concentrations. This anti-viral activity was equivalent to that of Tb, but lower than that of LL-37. Transcriptomic analyses revealed that SHa did not act through the modulation of the cell innate immune response, but rather, displayed virucidal properties by reducing infectious titer of HSV-1 in suspension. In contrast, pre-incubation of the virus with LL-37 suggests that this peptide does not act directly on the viral particle at non-cytotoxic concentrations tested. The anti-HSV-1 activity of LL-37 appears to be due to the potentiation of cellular anti-viral defenses through the induction of interferon stimulated gene expression in infected primary keratinocytes. This study demonstrated that SHa and [K3]SHa, in addition to their previously reported antibacterial and antiparasitic activities, are direct-acting anti-HSV-1 peptides. Importantly, this study extends the little studied anti-viral attributes of frog temporins and offers perspectives for the development of new anti-HSV-1 therapies.

ACS Style

Maëva Roy; Lucie Lebeau; Céline Chessa; Alexia Damour; Ali Ladram; Bruno Oury; David Boutolleau; Charles Bodet; Nicolas Lévêque. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1. Viruses 2019, 11, 77 .

AMA Style

Maëva Roy, Lucie Lebeau, Céline Chessa, Alexia Damour, Ali Ladram, Bruno Oury, David Boutolleau, Charles Bodet, Nicolas Lévêque. Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1. Viruses. 2019; 11 (1):77.

Chicago/Turabian Style

Maëva Roy; Lucie Lebeau; Céline Chessa; Alexia Damour; Ali Ladram; Bruno Oury; David Boutolleau; Charles Bodet; Nicolas Lévêque. 2019. "Comparison of Anti-Viral Activity of Frog Skin Anti-Microbial Peptides Temporin-Sha and [K3]SHa to LL-37 and Temporin-Tb against Herpes Simplex Virus Type 1." Viruses 11, no. 1: 77.

Comparative study
Published: 29 January 2017 in Journal of Clinical Virology
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EMAG™ (bioMerieux) is a new nucleic acid extraction platform based on magnetic silica technology, like its predecessor, NucliSENS® easyMAG® (bioMerieux). Using the same reagents and disposables, eMAG™ adds further automation, allowing simultaneous extraction of 48 samples directly from primary tubes, and distribution of nucleic acid extracts on PCR strips or in tubes at the end of the extraction process. To compare the performance of eMAG™ and easyMAG® on various clinical specimens. Respiratory (n = 199), whole blood (n = 50), plasma (n = 25) and urine (n = 25) specimens were extracted in parallel on both platforms. Both qualitative (respiratory virus, cell control, CMV, EBV, HHV6 and BKV detection) and quantitative (respiratory virus and cell control cycle thresolds, and CMV, EBV, HHV6 and BKV viral loads) results were compared. Detection of qualitative targets showed good agreement, ranging from 84.6% for whole blood to 95.9% for respiratory specimens. Correlations between quantitative results were good, with R2 ranging from 0.802 to 0.995. Quantitative results showed average overall differences below 0.10 log10 copies/mL between eMAG™ and easyMAG®. The two platforms showed comparable performance on the types of clinical specimen tested. With higher automation and throughput than easyMAG®, the eMAG™ platform is likely to be advantageous for laboratories performing a large number of molecular analyses.

ACS Style

Magali Garcia; Céline Chessa; Anne Bourgoin; Geneviève Giraudeau; Chloé Plouzeau; Gérard Agius; Nicolas Lévêque; Agnès Beby-Defaux. Comparison of eMAG™ versus NucliSENS® EasyMAG® performance on clinical specimens. Journal of Clinical Virology 2017, 88, 52 -57.

AMA Style

Magali Garcia, Céline Chessa, Anne Bourgoin, Geneviève Giraudeau, Chloé Plouzeau, Gérard Agius, Nicolas Lévêque, Agnès Beby-Defaux. Comparison of eMAG™ versus NucliSENS® EasyMAG® performance on clinical specimens. Journal of Clinical Virology. 2017; 88 ():52-57.

Chicago/Turabian Style

Magali Garcia; Céline Chessa; Anne Bourgoin; Geneviève Giraudeau; Chloé Plouzeau; Gérard Agius; Nicolas Lévêque; Agnès Beby-Defaux. 2017. "Comparison of eMAG™ versus NucliSENS® EasyMAG® performance on clinical specimens." Journal of Clinical Virology 88, no. : 52-57.

Short communication
Published: 09 November 2016 in Current Research in Translational Medicine
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Selenium deficiency adversely affects the clinical outcome of measles in the tropics. In developed countries, serum selenium level has never been investigated during acute measles. The aim of this study was to determine serum selenium concentrations in French patients with acute measles and to seek correlations with clinical and virological findings. We studied serum selenium concentrations in 94 French patients with acute measles and in 99 healthy controls matched for age and sex. The mean of selenium concentration was significantly lower in the patients than in the controls (46.4 ± 14.1 μg/L versus 86.5 ± 13.9 μg/L, P < 0.0001). In the patients, selenium concentrations were not associated with age, sex, vaccination status, clinical signs or specific antibody responses. Selenium levels did not differ significantly between patients with uncomplicated measles (45.8 ± 14.2 μg/L) and patients with complications (52.7 ± 13.2 μg/L) (P = 0.15). Acute measles is associated with significant reduction of selenium level that did not seem to negatively affect the course of the disease suggesting compensating mechanisms in patients from developed countries against the disease.

ACS Style

Magali Garcia; A. Pineau; O. Guillard; S. Ragot; N. Lévêque; G. Agius. Low serum selenium concentrations in French patients with measles. Current Research in Translational Medicine 2016, 65, 89 -91.

AMA Style

Magali Garcia, A. Pineau, O. Guillard, S. Ragot, N. Lévêque, G. Agius. Low serum selenium concentrations in French patients with measles. Current Research in Translational Medicine. 2016; 65 (2):89-91.

Chicago/Turabian Style

Magali Garcia; A. Pineau; O. Guillard; S. Ragot; N. Lévêque; G. Agius. 2016. "Low serum selenium concentrations in French patients with measles." Current Research in Translational Medicine 65, no. 2: 89-91.

Journal article
Published: 07 April 2016 in Transplant Infectious Disease
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Infectious diarrhea is a frequent complication after kidney transplantation (1). Following acute infection, long-term asymptomatic excretion, from several weeks to several months, of enteric pathogens as norovirus has been described in transplant recipients (2, 3). Nevertheless, risk factors of shedding remain still unknown. For this purpose, 56 stool samples from asymptomatic adult kidney transplant recipients were retrospectively tested with broad-spectrum molecular tests (xTAG GPP®, Luminex Molecular Diagnostics, Toronto, Canada) allowing the detection of the most common gastroenteritis-causing bacteria, parasites, and viruses (4).This article is protected by copyright. All rights reserved.

ACS Style

B. Schvartz; M. Garcia; A. Wolak‐Thierry; C. De Champs; Nicolas Leveque. Risk factors of asymptomatic shedding of enteric pathogens in renal transplant recipients. Transplant Infectious Disease 2016, 18, 480 -482.

AMA Style

B. Schvartz, M. Garcia, A. Wolak‐Thierry, C. De Champs, Nicolas Leveque. Risk factors of asymptomatic shedding of enteric pathogens in renal transplant recipients. Transplant Infectious Disease. 2016; 18 (3):480-482.

Chicago/Turabian Style

B. Schvartz; M. Garcia; A. Wolak‐Thierry; C. De Champs; Nicolas Leveque. 2016. "Risk factors of asymptomatic shedding of enteric pathogens in renal transplant recipients." Transplant Infectious Disease 18, no. 3: 480-482.

Journal article
Published: 01 April 2016 in Journal of Virological Methods
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Coxsackieviruses B (CV-B) (Picornaviridae) are a common infectious cause of acute myocarditis in children and young adults, a disease, which is a precursor to 10–20% of chronic myocarditis and dilated cardiomyopathy (DCM) cases. The mechanisms involved in the disease progression from acute to chronic myocarditis phase and toward the DCM clinical stage are not fully understood but are influenced by both viral and host factors. Subgenomic replicons of CV-B can be used to assess viral replication mechanisms in human cardiac cells and evaluate the effects of potential antiviral drugs on viral replication activities. Our objectives were to generate a reporter replicon from a cardiotropic prototype CV-B3/28 strain and to characterize its replication properties into human cardiac primary cells. To obtain this replicon, a cDNA plasmid containing the full CV-B3/28 genome flanked by a hammerhead ribozyme sequence and an MluI restriction site was generated and used as a platform for the insertion of sequences encoding emerald green fluorescent protein (EmGFP) in place of those encoding VP3. In vitro transcribed RNA from this plasmid was transfected into HeLa cells and human primary cardiac cells and was able to produce EmGFP and VP1-containing polypeptides. Moreover, non-structural protein biological activity was assessed by the specific cleavage of eIF4G1 by viral 2Apro. Viral RNA replication was indirectly demonstrated by inhibition assays, fluoxetine was added to cell culture and prevented the EmGFP synthesis. Our results indicated that the EmGFP CV-B3 replicon was able to replicate and translate as well as the CV-B3/28 prototype strain. Our EmGFP CV-B3 replicon will be a valuable tool to readily investigate CV-B3 replication activities in human target cell models.

ACS Style

Michel Wehbe; Antoine Huguenin; Nicolas Leveque; Bert L. Semler; Monzer Hamze; Laurent Andreoletti; Alexis Bouin. Construction of a subgenomic CV-B3 replicon expressing emerald green fluorescent protein to assess viral replication of a cardiotropic enterovirus strain in cultured human cells. Journal of Virological Methods 2016, 230, 1 -8.

AMA Style

Michel Wehbe, Antoine Huguenin, Nicolas Leveque, Bert L. Semler, Monzer Hamze, Laurent Andreoletti, Alexis Bouin. Construction of a subgenomic CV-B3 replicon expressing emerald green fluorescent protein to assess viral replication of a cardiotropic enterovirus strain in cultured human cells. Journal of Virological Methods. 2016; 230 ():1-8.

Chicago/Turabian Style

Michel Wehbe; Antoine Huguenin; Nicolas Leveque; Bert L. Semler; Monzer Hamze; Laurent Andreoletti; Alexis Bouin. 2016. "Construction of a subgenomic CV-B3 replicon expressing emerald green fluorescent protein to assess viral replication of a cardiotropic enterovirus strain in cultured human cells." Journal of Virological Methods 230, no. : 1-8.

Journal article
Published: 07 March 2016 in Expert Review of Anti-infective Therapy
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Magali Garcia; Agnès Beby-Defaux; Nicolas Leveque. Respiratory viruses as a cause of sudden death. Expert Review of Anti-infective Therapy 2016, 14, 359 -363.

AMA Style

Magali Garcia, Agnès Beby-Defaux, Nicolas Leveque. Respiratory viruses as a cause of sudden death. Expert Review of Anti-infective Therapy. 2016; 14 (4):359-363.

Chicago/Turabian Style

Magali Garcia; Agnès Beby-Defaux; Nicolas Leveque. 2016. "Respiratory viruses as a cause of sudden death." Expert Review of Anti-infective Therapy 14, no. 4: 359-363.

Comment
Published: 19 December 2015 in EBioMedicine
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Rubella virus (RV) is responsible for benign postnatal and deadly antenatal infections. Its involvement in developmental defects in children following congenital transmission was first made by Sir Norman McAlister Gregg in 1941. Indeed, the maternal primary infection results in an RV viremia and placental transfer. If it occurs before 12 weeks of gestation, during organogenesis, it can result in severe fetal damage causing miscarriage or malformations primarily affecting the cardiovascular system, eyes, ears and the central nervous system; it is fatal in nearly one third of cases during the first year of life (Töndury and Smith, 1966Töndury G. Smith D.W. Fetal rubella pathology.J. Pediatr. 1966; 68: 867-879Summary Full Text PDF PubMed Scopus (75) Google Scholar). This severe RV infection acquired in utero early in pregnancy is named as Congenital Rubella Syndrome or CRS. In 2014, 141 CRS cases were reported from 114 countries mostly from South-East Asia (n = 86/141), although reporting is probably inconsistent according to the authors themselves (Grant et al., 2015Grant G.B. Reef S.E. Dabbagh A. Gacic-Dobo M. Strebel P.M. Global progress toward rubella and congenital rubella syndrome control and elimination — 2000–2014.MMWR Morb. Mortal. Wkly Rep. 2015; 64: 1052-1055Crossref PubMed Scopus (25) Google Scholar). This number had been estimated as closer to 100,000 cases each year in developing countries alone (Cutts and Vynnycky, 1999Cutts F.T. Vynnycky E. Modelling the incidence of congenital rubella syndrome in developing countries.Int. J. Epidemiol. 1999; 28: 1176-1184Crossref PubMed Google Scholar). To better understand the pathogenesis of CRS in the absence of an animal model, the first histopathological explorations were conducted in some of the 20,000 fetuses infected during the 1964–1965 epidemics in the US when about 12.5 M Rubella cases were reported (National Communicable Disease Center, 1969National Communicable Disease Center Rubella Surveillance. US Department of Health, Education, and Welfare, Bethesda, MD1969Google Scholar). Although these studies identified histological lesions in the heart, blood vessels, crystalline lens, ears, brain, teeth and liver consistent with clinical features and sequelae of CRS, they did not solved the mechanisms of virus teratogenicity (Töndury and Smith, 1966Töndury G. Smith D.W. Fetal rubella pathology.J. Pediatr. 1966; 68: 867-879Summary Full Text PDF PubMed Scopus (75) Google Scholar, Esterly and Oppenheimer, 1969Esterly J.R. Oppenheimer E.H. Pathological lesions due to congenital rubella.Arch. Pathol. 1969; 87: 380-388PubMed Google Scholar). In particular, until recently, the exact nature of the cell types infected with RV remained unknown.

ACS Style

Magali Garcia; Agnès Beby-Defaux; Nicolas Lévêque. Localization of Viral Antigens Improves Understanding of Congenital Rubella Syndrome Pathophysiology. EBioMedicine 2015, 3, 8 -9.

AMA Style

Magali Garcia, Agnès Beby-Defaux, Nicolas Lévêque. Localization of Viral Antigens Improves Understanding of Congenital Rubella Syndrome Pathophysiology. EBioMedicine. 2015; 3 ():8-9.

Chicago/Turabian Style

Magali Garcia; Agnès Beby-Defaux; Nicolas Lévêque. 2015. "Localization of Viral Antigens Improves Understanding of Congenital Rubella Syndrome Pathophysiology." EBioMedicine 3, no. : 8-9.

Historical article
Published: 04 June 2015 in PLOS Pathogens
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Nicolas Leveque; Bert L. Semler. A 21st Century Perspective of Poliovirus Replication. PLOS Pathogens 2015, 11, e1004825 .

AMA Style

Nicolas Leveque, Bert L. Semler. A 21st Century Perspective of Poliovirus Replication. PLOS Pathogens. 2015; 11 (6):e1004825.

Chicago/Turabian Style

Nicolas Leveque; Bert L. Semler. 2015. "A 21st Century Perspective of Poliovirus Replication." PLOS Pathogens 11, no. 6: e1004825.

Journal article
Published: 21 May 2015 in Nephrology Dialysis Transplantation
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Betoul Schvartz; Nicolas Leveque. FP836ASYMPTOMATIC CARRIAGE OF GASTRO−INTESTINAL PATHOGENS IN RENAL TRANSPLANT RECIPIENTS : EPIDEMIOLOGY AND RISK FACTORS. Nephrology Dialysis Transplantation 2015, 30, 1 .

AMA Style

Betoul Schvartz, Nicolas Leveque. FP836ASYMPTOMATIC CARRIAGE OF GASTRO−INTESTINAL PATHOGENS IN RENAL TRANSPLANT RECIPIENTS : EPIDEMIOLOGY AND RISK FACTORS. Nephrology Dialysis Transplantation. 2015; 30 (suppl_3):1.

Chicago/Turabian Style

Betoul Schvartz; Nicolas Leveque. 2015. "FP836ASYMPTOMATIC CARRIAGE OF GASTRO−INTESTINAL PATHOGENS IN RENAL TRANSPLANT RECIPIENTS : EPIDEMIOLOGY AND RISK FACTORS." Nephrology Dialysis Transplantation 30, no. suppl_3: 1.

Journal article
Published: 01 March 2015 in Human Pathology
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Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis.

ACS Style

Valérie Leroux-Kozal; Nicolas Leveque; Véronique Brodard; Candice Lesage; Oriane Dudez; Marc Makeieff; Lukshe Kanagaratnam; Marie-Danièle Diebold. Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load. Human Pathology 2015, 46, 443 -453.

AMA Style

Valérie Leroux-Kozal, Nicolas Leveque, Véronique Brodard, Candice Lesage, Oriane Dudez, Marc Makeieff, Lukshe Kanagaratnam, Marie-Danièle Diebold. Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load. Human Pathology. 2015; 46 (3):443-453.

Chicago/Turabian Style

Valérie Leroux-Kozal; Nicolas Leveque; Véronique Brodard; Candice Lesage; Oriane Dudez; Marc Makeieff; Lukshe Kanagaratnam; Marie-Danièle Diebold. 2015. "Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load." Human Pathology 46, no. 3: 443-453.

Journal article
Published: 27 August 2014 in Journal of Medical Virology
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Complete coding regions were sequenced for two new enterovirus genomes: EV-B93 previously identified by VP1 sequencing, derived from a child with acute flaccid paralysis in the Democratic Republic of Congo; and EV-C95 from a French soldier with acute gastroenteritis in Djibouti. The EV-B93 P1 had more than 30% nucleotide divergence from other EV-B types, with highest similarity to E-15 and EV-B80. The P1 nucleotide sequence of EV-C95 was most similar, 71%, to CV-A21. Complete coding regions for the new enteroviruses were compared with those of 135 EV-B and 176 EV-C strains representing all types available in GenBank. When strains from the same outbreak or strains isolated during the same year in the same geographical region were excluded, 27 of the 58 EV-B, and 16 of the 23 EV-C types were represented by more than one sequence. However, for EV-B the P3 sequences formed three clades mainly according to origin or time of isolation, irrespective of type, while for EV-C the P3 sequences segregated mainly according to disease manifestation, with most strains causing paralysis, including polioviruses, forming one clade, and strains causing respiratory illness forming another. There was no intermixing of types between these two clades, apart from two EV-C96 strains. The EV-B P3 sequences had lower inter-clade and higher intra-clade variability as compared to the EV-C sequences, which may explain why inter-clade recombinations are more frequent in EV-B. Further analysis of more isolates may shed light on the role of recombinations in the evolution of EV-B in geographical context.

ACS Style

N. Junttila; Nicolas Leveque; L.O. Magnius; J.P. Kabue; J. J. Muyembe-Tamfum; J. Maslin; Bruno Lina; H. Norder. Complete coding regions of the prototypes enterovirus B93 and C95: Phylogenetic analyses of the P1 and P3 regions of EV-B and EV-C strains. Journal of Medical Virology 2014, 87, 485 -497.

AMA Style

N. Junttila, Nicolas Leveque, L.O. Magnius, J.P. Kabue, J. J. Muyembe-Tamfum, J. Maslin, Bruno Lina, H. Norder. Complete coding regions of the prototypes enterovirus B93 and C95: Phylogenetic analyses of the P1 and P3 regions of EV-B and EV-C strains. Journal of Medical Virology. 2014; 87 (3):485-497.

Chicago/Turabian Style

N. Junttila; Nicolas Leveque; L.O. Magnius; J.P. Kabue; J. J. Muyembe-Tamfum; J. Maslin; Bruno Lina; H. Norder. 2014. "Complete coding regions of the prototypes enterovirus B93 and C95: Phylogenetic analyses of the P1 and P3 regions of EV-B and EV-C strains." Journal of Medical Virology 87, no. 3: 485-497.

Evaluation study
Published: 06 November 2013 in Journal of Clinical Microbiology
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Viruses are the leading cause of central nervous system (CNS) infections, ahead of bacteria, parasites, and fungal agents. A rapid and comprehensive virologic diagnostic testing method is needed to improve the therapeutic management of hospitalized pediatric or adult patients. In this study, we assessed the clinical performance of PCR amplification coupled with electrospray ionization-time of flight mass spectrometry analysis (PCR-MS) for the diagnosis of viral CNS infections. Three hundred twenty-seven cerebrospinal fluid (CSF) samples prospectively tested by routine PCR assays between 2004 and 2012 in two university hospital centers (Toulouse and Reims, France) were retrospectively analyzed by PCR-MS analysis using primers targeted to adenovirus, human herpesviruses 1 to 8 (HHV-1 to -8), polyomaviruses BK and JC, parvovirus B19, and enteroviruses (EV). PCR-MS detected single or multiple virus infections in 190 (83%) of the 229 samples that tested positive by routine PCR analysis and in 10 (10.2%) of the 98 samples that tested negative. The PCR-MS results correlated well with herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV), and EV detection by routine PCR assays (kappa values [95% confidence intervals], 0.80 [0.69 to 0.92], 0.85 [0.71 to 0.98], and 0.84 [0.78 to 0.90], respectively), whereas a weak correlation was observed with Epstein-Barr virus (EBV) (0.34 [0.10 to 0.58]). Twenty-six coinfections and 16 instances of uncommon neurotropic viruses (HHV-7 [n = 13], parvovirus B19 [n = 2], and adenovirus [n = 1]) were identified by the PCR-MS analysis, whereas only 4 coinfections had been prospectively evidenced using routine PCR assays (P < 0.01). In conclusion, our results demonstrated that PCR-MS analysis is a valuable tool to identify common neurotropic viruses in CSF (with, however, limitations that were identified regarding EBV and EV detection) and may be of major interest in better understanding the clinical impact of multiple or neglected viral neurological infections.

ACS Style

Nicolas Lévêque; Jérôme LeGoff; Catherine Mengelle; Séverine Mercier-Delarue; Yohan N'guyen; Fanny Renois; Fabien Tissier; François Simon; Jacques Izopet; Laurent Andreoletti. Virological Diagnosis of Central Nervous System Infections by Use of PCR Coupled with Mass Spectrometry Analysis of Cerebrospinal Fluid Samples. Journal of Clinical Microbiology 2013, 52, 212 -217.

AMA Style

Nicolas Lévêque, Jérôme LeGoff, Catherine Mengelle, Séverine Mercier-Delarue, Yohan N'guyen, Fanny Renois, Fabien Tissier, François Simon, Jacques Izopet, Laurent Andreoletti. Virological Diagnosis of Central Nervous System Infections by Use of PCR Coupled with Mass Spectrometry Analysis of Cerebrospinal Fluid Samples. Journal of Clinical Microbiology. 2013; 52 (1):212-217.

Chicago/Turabian Style

Nicolas Lévêque; Jérôme LeGoff; Catherine Mengelle; Séverine Mercier-Delarue; Yohan N'guyen; Fanny Renois; Fabien Tissier; François Simon; Jacques Izopet; Laurent Andreoletti. 2013. "Virological Diagnosis of Central Nervous System Infections by Use of PCR Coupled with Mass Spectrometry Analysis of Cerebrospinal Fluid Samples." Journal of Clinical Microbiology 52, no. 1: 212-217.

Case reports
Published: 19 August 2013 in Journal of Medical Virology
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Measles is a highly contagious viral infection causing congenital infections with a risk of neurological complications in the newborn. Two cases of measles, which occurred in pregnant women within 14 days before the delivery, are described. Mother-to-child transmission of the virus was documented in the newborns either by RT-PCR in saliva or by IgM detection in blood. The measles strains evidenced in saliva samples were genotyped and belonged to the D4 Genotype. An early viral RT-PCR detection allowed successful immunoglobulin prophylaxis in one newborn taking into account that the duration between the onset of the skin rash in the mother and the delivery was less than 6 days. Twenty-four months later, none of the newborns developed classical or neurological clinical signs of measles infection. Measles RT-PCR assay in salivary samples can be used before symptoms develop in the infant to confirm early mother-to-child transmission, therefore permitting the use of an immunoglobulin prophylaxis in the newborn.

ACS Style

Delphine Giusti; Julie Burette; Yohan Nguyen; Nicolas Leveque; Olivier Graesslin; Laurent Andreoletti. Virological diagnosis and management of two cases of congenital measles. Journal of Medical Virology 2013, 85, 2136 -2138.

AMA Style

Delphine Giusti, Julie Burette, Yohan Nguyen, Nicolas Leveque, Olivier Graesslin, Laurent Andreoletti. Virological diagnosis and management of two cases of congenital measles. Journal of Medical Virology. 2013; 85 (12):2136-2138.

Chicago/Turabian Style

Delphine Giusti; Julie Burette; Yohan Nguyen; Nicolas Leveque; Olivier Graesslin; Laurent Andreoletti. 2013. "Virological diagnosis and management of two cases of congenital measles." Journal of Medical Virology 85, no. 12: 2136-2138.

Case report
Published: 15 August 2013 in Journal of Clinical Virology
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An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella. To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death. Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology. Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6 × 107 and 1.9 × 105 genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues. This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death.

ACS Style

Aurore Desmons; Caroline Terrade; Camille Boulagnon; Delphine Giusti; Yohan Nguyen; Laurent Andreoletti; Paul Fornes; Béatrice Digeon; Nicolas Leveque. Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death. Journal of Clinical Virology 2013, 58, 486 -489.

AMA Style

Aurore Desmons, Caroline Terrade, Camille Boulagnon, Delphine Giusti, Yohan Nguyen, Laurent Andreoletti, Paul Fornes, Béatrice Digeon, Nicolas Leveque. Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death. Journal of Clinical Virology. 2013; 58 (2):486-489.

Chicago/Turabian Style

Aurore Desmons; Caroline Terrade; Camille Boulagnon; Delphine Giusti; Yohan Nguyen; Laurent Andreoletti; Paul Fornes; Béatrice Digeon; Nicolas Leveque. 2013. "Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death." Journal of Clinical Virology 58, no. 2: 486-489.

Evaluation study
Published: 01 June 2013 in Journal of Clinical Microbiology
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Diarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively ( P = 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic Escherichia coli (EPEC) ( n = 15; 38%), Campylobacter spp. ( n = 15; 38%), and Norovirus ( n = 14; 36%). Specificities for Campylobacter and Norovirus infection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing Norovirus -induced diarrhea. Norovirus infections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not Norovirus and Campylobacter infections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.

ACS Style

Jean-François Coste; Vincent Vuiblet; Betoul Moustapha; Alexis Bouin; Sylvie Lavaud; Olivier Toupance; Alexis de Rougemont; Lucie Benejat; Francis Megraud; Aurore Wolak-Thierry; Isabelle Villena; Cathy Chemla; Elisabeth Le Magrex; Christophe de Champs; Laurent Andreoletti; Philippe Rieu; Nicolas Leveque. Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays. Journal of Clinical Microbiology 2013, 51, 1841 -1849.

AMA Style

Jean-François Coste, Vincent Vuiblet, Betoul Moustapha, Alexis Bouin, Sylvie Lavaud, Olivier Toupance, Alexis de Rougemont, Lucie Benejat, Francis Megraud, Aurore Wolak-Thierry, Isabelle Villena, Cathy Chemla, Elisabeth Le Magrex, Christophe de Champs, Laurent Andreoletti, Philippe Rieu, Nicolas Leveque. Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays. Journal of Clinical Microbiology. 2013; 51 (6):1841-1849.

Chicago/Turabian Style

Jean-François Coste; Vincent Vuiblet; Betoul Moustapha; Alexis Bouin; Sylvie Lavaud; Olivier Toupance; Alexis de Rougemont; Lucie Benejat; Francis Megraud; Aurore Wolak-Thierry; Isabelle Villena; Cathy Chemla; Elisabeth Le Magrex; Christophe de Champs; Laurent Andreoletti; Philippe Rieu; Nicolas Leveque. 2013. "Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays." Journal of Clinical Microbiology 51, no. 6: 1841-1849.