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viral queratitis

Rolando Cannalire, Delia Tarantino, Andrea Astolfi, Maria Letizia Barreca, Stefano Sabatini, Serena Massari, Oriana Tabarrini, Mario Milani, Gilles Querat, Eloise Mastrangelo, Giuseppe Manfroni, Violetta Cecchetti
Over recent years, many RNA viruses have been "re-discovered", including life-threatening flaviviruses, such as Dengue, Zika, and several encephalitis viruses. Since no specific inhibitors are currently available to treat these infections, there is a pressing need for new therapeutics. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) represents a validated target being essential for viral replication and it has no human analog. To date, few NS5 RdRp inhibitor chemotypes have been reported and no inhibitors are currently in clinical development...
January 1, 2018: European Journal of Medicinal Chemistry
Abdennour Amroun, Stéphane Priet, Gilles Querat
Toscana virus (TOSV) is an arthropod-borne phlebovirus within the family Phenuiviridae in the order Bunyavirales. It seems to be an important agent of human meningoencephalitis in the warm season in the Mediterranean area. Because the polymerase of Bunyavirales lacks a capping activity, it cleaves short-capped RNA leaders derived from the host cell, and uses them to initiate viral mRNA synthesis. To determine the size and nucleotide composition of the host-derived RNA leaders, and to elucidate the first steps of TOSV transcription initiation, we performed a high-throughput sequencing of the 5' end of TOSV mRNAs in infected cells at different times post-infection...
October 12, 2017: Journal of General Virology
Wahiba Aouadi, Cécilia Eydoux, Bruno Coutard, Baptiste Martin, Françoise Debart, Jean Jacques Vasseur, Jean Marie Contreras, Christophe Morice, Gilles Quérat, Marie-Louise Jung, Bruno Canard, Jean-Claude Guillemot, Etienne Decroly
Two highly pathogenic human coronaviruses associated with severe respiratory syndromes emerged since the beginning of the century. The severe acute respiratory syndrome SARS-coronavirus (CoV) spread first in southern China in 2003 with about 8000 infected cases in few months. Then in 2012, the Middle East respiratory syndrome (MERS-CoV) emerged from the Arabian Peninsula giving a still on-going epidemic associated to a high fatality rate. CoVs are thus considered a major health threat. This is especially true as no vaccine nor specific therapeutic are available against either SARS- or MERS-CoV...
August 2017: Antiviral Research
Alba Gigante, Asier Gómez-SanJuan, Leen Delang, Changqing Li, Oskía Bueno, Ana-María Gamo, Eva-María Priego, María-José Camarasa, Dirk Jochmans, Pieter Leyssen, Etienne Decroly, Bruno Coutard, Gilles Querat, Johan Neyts, María-Jesús Pérez-Pérez
Chikungunya virus (CHIKV) is a re-emerging alphavirus transmitted to humans by Aedes mosquitoes. Since 2005, CHIKV has been spreading worldwide resulting in epidemics in Africa, the Indian Ocean islands, Asia and more recently in the Americas. CHIKV is thus considered as a global health concern. There is no specific vaccine or drug available for the treatment of this incapacitating viral infection. We previously identified 3-aryl-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones as selective inhibitors of CHIKV replication and proposed the viral capping enzyme nsP1 as a target...
August 2017: Antiviral Research
Abdennour Amroun, Stéphane Priet, Xavier de Lamballerie, Gilles Quérat
Bunyaviridae family is the largest and most diverse family of RNA viruses. It has more than 350 members divided into five genera: Orthobunyavirus, Phlebovirus, Nairovirus, Hantavirus, and Tospovirus. They are present in the five continents, causing recurrent epidemics, epizootics, and considerable agricultural loss. The genome of bunyaviruses is divided into three segments of negative single-stranded RNA according to their relative size: L (Large), M (Medium) and S (Small) segment. Bunyaviridae RNA-dependent RNA polymerase (RdRp) is encoded by the L segment, and is in charge of the replication and transcription of the viral RNA in the cytoplasm of the infected cell...
November 2017: Critical Reviews in Microbiology
L Delang, C Li, A Tas, G Quérat, I C Albulescu, T De Burghgraeve, N A Segura Guerrero, A Gigante, G Piorkowski, E Decroly, D Jochmans, B Canard, E J Snijder, M J Pérez-Pérez, M J van Hemert, B Coutard, P Leyssen, J Neyts
The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping...
August 22, 2016: Scientific Reports
Fatiha Benmansour, Cécilia Eydoux, Gilles Querat, Xavier de Lamballerie, Bruno Canard, Karine Alvarez, Jean-Claude Guillemot, Karine Barral
Using a functional high-throughput screening (HTS) and subsequent SAR studies, we have discovered a novel series of non-nucleoside dengue viral polymerase inhibitors. We report the elaboration of SAR around hit compound 1 as well as the synthesis and antiviral evaluation of 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole and 5-phenyl-2-[2-(2-thienyl)ethenyl]-1,3,4-oxadiazole analogues derived from a rapid and easily accessible chemical pathway. A large number of compounds prepared by this method were shown to possess in vitro activity against the polymerase of dengue virus...
February 15, 2016: European Journal of Medicinal Chemistry
Fabien Aubry, Antoine Nougairède, Lauriane de Fabritus, Gilles Querat, Ernest A Gould, Xavier de Lamballerie
Reverse genetics is a key methodology for producing genetically modified RNA viruses and deciphering cellular and viral biological properties, but methods based on the preparation of plasmid-based complete viral genomes are laborious and unpredictable. Here, both wild-type and genetically modified infectious RNA viruses were generated in days using the newly described ISA (infectious-subgenomic-amplicons) method. This new versatile and simple procedure may enhance our capacity to obtain infectious RNA viruses from PCR-amplified genetic material...
November 2014: Journal of General Virology
Leen Delang, Nidya Segura Guerrero, Ali Tas, Gilles Quérat, Boris Pastorino, Mathy Froeyen, Kai Dallmeier, Dirk Jochmans, Piet Herdewijn, Felio Bello, Eric J Snijder, Xavier de Lamballerie, Byron Martina, Johan Neyts, Martijn J van Hemert, Pieter Leyssen
OBJECTIVES: T-705, also known as favipiravir, is a small-molecule inhibitor that is currently in clinical development for the treatment of influenza virus infections. This molecule also inhibits the replication of a broad spectrum of other RNA viruses. The objective of this study was to investigate the antiviral effect of favipiravir on chikungunya virus (CHIKV) replication and to contribute to unravelling the molecular mechanism of action against this virus. METHODS: The anti-CHIKV effect of favipiravir was examined in cell culture and in a mouse model of lethal infection...
October 2014: Journal of Antimicrobial Chemotherapy
S Lagarde, J-C Lagier, R Charrel, G Quérat, J Vanhomwegen, P Desprès, J Pelletier, E Kaphan
Japanese encephalitis is frequent in Asia, with a severe prognosis, but rare in travelers. Culex mosquitoes transmit Japanese encephalitis virus. Risk factors are destination, duration of stay, summer and fall seasons, outdoor activities, and type of accommodation. We report the case of a French traveler to Nepal with neutralization-based serological confirmed Japanese encephalitis. He presented classical clinical (viral syndrome before an encephalitis status with behavioral disorder, global hypotonia, mutism, movement disorders, seizure, and coma), radiological (lesions of thalami, cortico-spinal tracts, and brainstem) and biological features (lymphocytic meningitis)...
February 2014: Journal of Neurovirology
Cécile Baronti, Joséphine Sire, Xavier de Lamballerie, Gilles Quérat
Flaviviruses are single-stranded positive RNA viruses that replicate through double stranded RNA (dsRNA) intermediates. These dsRNA may be recognized as pathogen-associated molecular patterns by cellular receptors including membrane-bound Toll-like receptor 3 (TLR3) and cytosolic helicases RIG-I and MDA5. dsRNA stimulation results in signaling cascades converging to activation of interferon (IFN) regulatory factor 3 (IRF3) and to transcriptional activation of several interferon stimulated genes, including IFNss and inflammatory cytokines...
September 1, 2010: Virology
Joséphine Sire, Gilles Quérat, Cécile Esnault, Stéphane Priet
Uracil is a natural base of RNA but may appear in DNA through two different pathways including cytosine deamination or misincorporation of deoxyuridine 5'-triphosphate nucleotide (dUTP) during DNA replication and constitutes one of the most frequent DNA lesions. In cellular organisms, such lesions are faithfully cleared out through several universal DNA repair mechanisms, thus preventing genome injury. However, several recent studies have brought some pieces of evidence that introduction of uracil bases in viral genomic DNA intermediates during genome replication might be a way of innate immune defence against some viruses...
2008: Retrovirology
Stéphane Priet, Joséphine Sire, Gilles Quérat
Uracil in DNA is a deleterious event that may arise either by cytosine deamination or misincorporation of dUTP. Consequently, cells from all free-living organisms have developed strategies to protect their genome against the presence of uracils, by using uracil DNA glycosylase (UNG) and deoxyuridine triphosphatase (dUTPase) enzymatic activities. In the viral kingdom, some (namely poxviruses and herpesviruses) but not all of the DNA viruses encode their own UNG and dUTPase to control uracilation of their genome...
January 2006: Current HIV Research
Stéphane Priet, Nathalie Gros, Jean-Marc Navarro, Joëlle Boretto, Bruno Canard, Gilles Quérat, Joséphine Sire
Uracilation of DNA represents a constant threat to the survival of many organisms including viruses. Uracil may appear in DNA either by cytosine deamination or by misincorporation of dUTP. The HIV-1-encoded Vif protein controls cytosine deamination by preventing the incorporation of host-derived APOBEC3G cytidine deaminase into viral particles. Here, we show that the host-derived uracil DNA glycosylase UNG2 enzyme, which is recruited into viral particles by the HIV-1-encoded integrase domain, is essential to the viral life cycle...
February 18, 2005: Molecular Cell
Stéphane Priet, Jean-Marc Navarro, Gilles Quérat, Joséphine Sire
The human immunodeficiency virus type 1 (HIV-1) integrase (IN) is essential for integration of viral DNA into host cell chromatin. We have reported previously (Priet, S., Navarro, J. M., Gros, N., Querat, G., and Sire, J. (2003) J. Biol. Chem. 278, 4566-4571) that IN also plays a role in the packaging of the host uracil DNA glycosylase UNG2 into viral particles and that the region of IN encompassing residues 170-180 was responsible for the interaction with UNG2 and for its packaging into virions. In this work, we aimed to investigate the replication of HIV-1 viruses rendered deficient in virion-associated UNG2 by single or double point mutations in the region 170-180 of IN...
June 6, 2003: Journal of Biological Chemistry
Stéphane Priet, Jean-Marc Navarro, Nathalie Gros, Gilles Quérat, Joséphine Sire
We have previously reported that the host uracil DNA glycosylase UNG2 enzyme is incorporated into HIV-1 virions via a specific association with the viral integrase (IN) domain of Gag-Pol precursor. In this study, we investigated whether UNG2 was packaged into two phylogenetically closely related primate lentiviruses, HIV-2(ROD) and SIV(MAC239). We demonstrated by GST-pull-down and coprecipitation assays that INs from HIV-1, HIV-2(ROD), and SIV(MAC239) associated with UNG2, although the interaction of UNG2 with HIV-2(ROD) IN and SIV(MAC239) IN was less strong than with HIV-1 IN...
March 15, 2003: Virology
D F York, G Querat
Jaagsiekte (JS), a contagious cancer affecting the lungs of sheep has been called many names over the years. At a recent workshop in Missilac, France it was agreed that the disease would be called ovine pulmonary adenocarcinoma (OPA). The disease is caused by an infectious retrovirus called jaagsiekte sheep retrovirus (JSRV). This chapter focuses on the early research that led up to the isolation, cloning and sequencing of the exogenous infectious form of JSRV and the demonstration that it has an endogenous counter part that is present in all sheep...
2003: Current Topics in Microbiology and Immunology
Stephane Priet, Jean-Marc Navarro, Nathalie Gros, Gilles Querat, Josephine Sire
Human monocytes/macrophages are target cells for HIV-1 infection. As other non-dividing cells, they are characterized by low and imbalanced intracellular dNTP pool levels and an excess of dUTP. The replication of HIV-1 in this cellular context favors misincorporation of uracil residues into viral DNA because of the use of dUTP in place of dCTP. We have previously reported that the host uracil DNA glycosylase enzyme UNG2 is packaged into HIV-1 viral particles via a specific association with the integrase domain of the Gag-Pol precursor...
February 14, 2003: Journal of Biological Chemistry
J M Navarro, L Damier, J Boretto, S Priet, B Canard, G Quérat, J Sire
The biological form of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a heterodimer consisting of two polypeptides, p66 and p51, which have identical N-termini. The p51 polypeptide is generated by action of viral protease cleaving the p66 polypeptide between residues Phe440 and Tyr441. Dimerization has been mostly studied using bacterially purified RT bearing amino acid changes in either subunit, but not in the context of HIV-1 particles. We introduced changes of conserved amino acid residues 430-438 into the protease-sensitive subdomain of the p66 subunit and analyzed the reverse transcriptase processing and function using purified variants and their corresponding HIV-1 recombinant clones...
November 25, 2001: Virology
L Mselli-Lakhal, C Favier, K Leung, F Guiguen, D Grezel, P Miossec, J F Mornex, O Narayan, G Querat, Y Chebloune
Barriers to replication of viruses in potential host cells may occur at several levels. Lack of suitable and functional receptors on the host cell surface, thereby precluding entry of the virus, is a frequent reason for noninfectivity, as long as no alternative way of entry (e.g., pinocytosis, antibody-dependent adsorption) can be exploited by the virus. Other barriers can intervene at later stages of the virus life cycle, with restrictions on transcription of the viral genome, incorrect translation and posttranslational processing of viral proteins, inefficient viral assembly, and release or efficient early induction of apoptosis in the infected cell...
September 2000: Journal of Virology
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