DOCSLIB.ORG

Approches Bioinformatiques Et Structurales Des Replicases Virales Francois Ferron

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Approches Bioinformatiques Et Structurales Des Replicases Virales Francois Ferron Approches bioinformatiques et structurales des replicases virales Francois Ferron To cite this version: Francois Ferron. Approches bioinformatiques et structurales des replicases virales. Autre [q-bio.OT]. Université de la Méditerranée - Aix-Marseille II, 2005. Français. tel-00010419v1 HAL Id: tel-00010419 https://tel.archives-ouvertes.fr/tel-00010419v1 Submitted on 5 Oct 2005 (v1), last revised 7 Oct 2005 (v2) HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université de la Méditerranée Aix- Marseille II Faculté des Sciences de Luminy THESE DE DOCTORAT Ecole Doctorale des Sciences de la Vie et de la Santé Présentée par François-Patrice FERRON en vue d’obtenir le grade de docteur de l’Université de la Méditerranée Approches bioinformatiques et structurales des réplicases virales Soutenance soutenue le 04 février 2005 devant la commission d’examen: Pr Jean-Louis ROMETTE Président de Jury Dr Olivier POCH Rapporteur Dr Félix REY Rapporteur Dr Denis GERLIER Examinateur Dr Sonia LONGHI Co-Directeur de thèse Dr Bruno CANARD Directeur de thèse 1 Ils ne savaient pas que c'était impossible, alors ils l'ont fait. Mark Twain 2 Remerciements Je tiens à remercier vivement les membres du jury, M. Olivier Poch, M. Félix Rey, M. Denis Gerlier et M. Jean-Louis Romette pour l’honneur qu’ils me font de juger cette thèse. Je tiens à remercier la Commission de la Communauté Européenne pour son soutien financier dans le cadre des programmes VirRNADrugPolTarget et SPINE. Je remercie Christian Cambillau et Bernard Henrissat de m’avoir accueilli au sein du laboratoire et soutenu toutes ces années. Je voudrais exprimer ma gratitude à Bruno Canard pour m’avoir accueilli dans son équipe, pour sa confiance, sa compréhension, son encadrement et tous ces morceaux de musiques partagés. Merci Bruno, j’ai apprécié le degré de liberté que tu m’as laissé tout en étant là quand j’en avais besoin ! Ma reconnaissance va également à Sonia Longhi pour son encadrement, sa patience (dont j’ai si souvent abusé), sa gentillesse, sa disponibilité, son sens pédagogique et son aide constante. Cela été un réel plaisir de travailler avec toi ! Joelle Boretto pour son aide, ses conseils et sa bonne humeur constante qui donne la pêche. Joelle surtout ne change pas. Corinne Rancurel pour sa gentillesse, sa disponibilité et sa patience pendant ces années durant lesquelles elle a dû me subir. Corinne, sans toi rien n’aurait été possible ! David Karlin pour ses milliers d’idées (qui fusent dans tous les sens), pour son enthousiasme, sa disponibilité, sa volonté pédagogique et son soutien. Barbara Sélisko pour sa gentillesse, sa disponibilité, son soutien pendant ces quatre années et pour toutes les discussions passionnées et passionnantes qu’on a eu. Karine Alvarez pour sa disponibilité, son soutien, son sourire et son enthousiasme fantastique. Kenth Hallberg (précédemment Johansson) pour tous nos moments de travail et les autres … . Jean-Marie Bourhis pour son soutien, son humour, sa bonne humeur et sa vivacité d’esprit. Ce fût un plaisir de partager tous ces moments qui resteront gravés dans ma mémoire (je vais acheter un bloc de marbre au cas où !). Un grand merci à Isabelle Imbert pour son aide, son dynamisme, sa joie de vivre, et son soutien constant. Toute cette bonne humeur qui fait s’envoler les 3 soucis, Isa change pas ! Je remercie Céline De Michelis pour son soutien et sa gentillesse au cours de ces années, bonne chance pour la suite. Claire Debarnot pour son humour, et son dynamisme. Marie-Pierre Egloff pour son soutien constant au cours de ces quatre années et son encadrement précieux au synchrotron. Hélène Dutartre pour ses conseils et sa disponibilité. Jean-Claude Guillemot pour son aide et ses conseils. Delphine Benarroch, pour sa disponibilité et sa gentillesse tout au long de cette thèse. Antoine Frangeul pour son soutien, je suis sûr que bientôt tu vas avoir la main verte pour faire pousser les cristaux ! Cécile Bussetta pour son soutien, sa vivacité d’esprit, sa disponibilité et ces longues discussions. Karine Barral pour sa gentillesse et sa disponibilité. A tous ceux qui sont et sont passés dans le bureau 8, merci pour tous ces moments, vous avez contribué à changer cette sombre pièce en bureau convivial. Valérie Campanacci pour son aide précieuse au cours de cette dernière année. Merci à toute l’équipe de glycobiologie du laboratoire de nous avoir parrainé et aidé dans cette aventure. Je remercie tous les membres de l’équipe, passés ou présents. Jean-Louis, Karine, Boulbaba, Jérôme, Magali, Coralie, Marielle, Ling, Nadia, Deborah, Fred, Philippe. Merci à tous pour votre bonne humeur. Merci à Eric Blanc, Philippe Cantau, Luciana de Stéphanis, France Chassary, Aurore, pour leur gentillesse et efficacité. Merci à toutes les personnes de la plateforme SPINE, qui m’ont aidé et gentiment accueilli parmi eux. Merci à Jérôme Courcambeck pour son soutien et son aide. Merci à Emmanuel Courcelle et Patrice Gouet qui pour leurs aides. Merci, pour leurs encouragements, et leur soutien indéfectible Jean-Christophe, Sandrine, Jean-Bernard, Latifa, Jérôme, Céline, Fabienne, Olivier, Raphaël, Cent, Emir, Anne, Emeline, David, Maria, Jean-Pierre, YoYo, Valérie, Marie. Toutes ces tranches de vie ou folles soirées ne seront jamais oubliées, c’est que du bonheur et le plus beau reste à venir !!! Merci, à Rofia pour son soutien et ses encouragements ! Merci à ma famille pour son soutien inconditionnel. Vous avez partagé tous ces moments d’excitations scientifiques et les passages à vides. Ce travail vous est dédié… 4 Liste des Abréviations aa Acide aminé Å! Angström ADN Acide désoxyribonucléique ARN Acide ribonucléique ATP Adénosine tri phosphate BLAST Basic Local Alignment Search Tool. (Altschul et al.) : Algorithme de comparaison de séquences utilisé pour effectuer des recherches dans les banques en utilisant des alignements locaux. BLOSUM Matrice de substitution dans laquelle les valeurs sont dérivées de l'observation des fréquences de substitution dans des familles de protéines alignées. C Protéine de Capside C-terminal Carboxy-terminal DC Dichroïsme Circulaire Dis Désordonné DLS (Dynamic light Scattering) Diffusion dynamique de la lumière E-value (Expect value) Nombre d’alignements différents ayant un score égal ou supérieur S que l'on peut espérer trouver par hasard dans les banques. Plus la E-value est basse, plus le score est significatif (BLAST). F Protéine de Fusion FASTA premier algorithme de recherche de similarité couramment utilisé. GTP Guanosine triphosphate H Protéine d’attachement HCA (Hydrophobic Cluster analysis) Analyse des amas hydrophobes HD Domaine hydrophobe Indels Espace introduit dans un alignement pour contre balancer une insertion dans une autre séquence. kb Kilo bases kDa Kilo Dalton L Protéine L incluant la polymérase et une méthyltransférase M Protéine de Matrice Mb Mega bases MD Domaine de multimérisation N Nucléoprotéine NCBI National Center for Biotechnology Information NS Protéine non structurale N-terminal Amino-terminal NTP Nucléotide triphosphate OMS Organisation Mondiale de la Santé P Phosphoprotéine PAGE Poly Acrylamide Gel Electrophoresis PAM (Percent Accepted Mutation) Unité introduite par Dayhoff pour quantifier les changements dus à l'évolution dans une séquence protéique. PSI-BLAST (Position-Specific Iterated BLAST) : algorithme permettant une recherche itérative en utilisant BLAST. P-value Probabilité qu'un alignement apparaisse avec un score égal ou supérieur à un score donné. Les P-value les plus significatives sont celles proches de zéro. Les P-values et les E-values diffèrent dans la manière de représenter la significativité de l'alignement. RN Réseaux neuronaux Se Score élémentaire SeV Virus de Sendai Sp Score de pénalité SRAS Syndrome Respiratoire Aiguë Sévère TM Domaine transmembranaire UNK Domaine inconnu VSV Virus de la Stomatite Vésiculaire 5 Résumé La virologie bénéficie de plus en plus du développement de la bioinformatique. Mon projet de thèse recouvre la gestion de séquences de protéines se rapportant aux virus à ARN simple brin, de polarité négative et positive. J’ai mis en place une base de données VaZyMolO, qui gère les informations structurales et fonctionnelles des protéines, en définissant et en classant des modules. Cette approche a permis l’identification d’un domaine méthyltransférase sur la protéine L des Mononegavirales, et la définition de la modularité des protéines N et P des Paramyxoviridae. La cartographie du génome du virus du Syndrome Respiratoire Aigue Sévère réalisée à l’aide de VaZyMolO, a contribué à la résolution structurale de la protéine nsp9 de ce virus. Enfin, je présente une étude incluant évolution et analyse structurale des polymérases des Flaviviridae. Dans cette dernière, je propose un modèle de la polymérase du virus GBV-C et un mécanisme d’initiation de la synthèse d’ARN. Abstract Virology is increasingly benefiting from bio-informatics approaches. My thesis project concerns the study of protein sequences from single stranded, negative and positive RNA viruses. I have set up VaZyMolO, a database that deals with proteins at a functional and structural level. Based on similarity, it is a tool that defines and classifies protein modules. This approach contributed to the identification of a methyltransferase domain on L proteins of Mononegavirales, and to the definition of the N and P modularity in Paramyxoviridae. The mapping of the Severe Acute Respiratory Syndrome virus genome using VaZyMolO contributed to the structural definition of the nsp9 protein of this virus. My thesis also presents an analysis of the Flaviviridae polymerases.
Load more

Recommended publications
  • Chorioméningite Lymphocytaire, Tuberculose, Échinococcose…
    LES ZOONOSES INFECTIEUSES Juin 2021 Ce document vous est offert par Boehringer Ingelheim Ce fascicule fait partie de l’ensemble des documents polycopiés rédigés de manière concertée par des enseignants de maladies contagieuses des quatre Ecoles nationales vétérinaires françaises, à l’usage des étudiants vétérinaires. Sa rédaction et sa mise à jour régulière ont été sous la responsabilité de B. Toma jusqu’en 2006, avec la contribution, pour les mises à jour, de : G. André-Fontaine, M. Artois, J.C. Augustin, S. Bastian, J.J. Bénet, O. Cerf, B. Dufour, M. Eloit, N. Haddad, A. Lacheretz, D.P. Picavet, M. Prave La mise à jour est réalisée depuis 2007 par N. Haddad La citation bibliographique de ce fascicule doit être faite de la manière suivante : Haddad N. et al. Les zoonoses infectieuses, Polycopié des Unités de maladies réglementées des Ecoles vétérinaires françaises, Boehringer Ingelheim (Lyon), juin 2021, 217 p. Nous remercions Boehringer Ingelheim qui, depuis de nombreuses années, finance et assure la réalisation de ce polycopié. * 1 2 OBJECTIFS D’APPRENTISSAGE Rang A (libellé souligné) et rang B A l’issue de cet enseignement, les étudiants devront être capables : • de répondre à des questions posées par une personne (propriétaire d'animaux, médecin...) relatives à la nature des principales maladies bactériennes et virales transmissibles à l'Homme lors de morsure par un carnivore . • de répondre à des questions posées par une personne (propriétaire d'animaux, médecin...) relatives à l'évolution de la maladie chez l'Homme, les modalités de la transmission et de la prévention des principales maladies bactériennes et virales transmissibles à l'Homme à partir des carnivores domestiques et les grandes lignes de leur prophylaxie.
    [Show full text]
  • Diapositiva 1
    Simultaneous outbreak of Dengue and Chikungunya in Al Hodayda, Yemen (epidemiological and phylogenetic findings) Giovanni Rezza1, Gamal El-Sawaf2, Giovanni Faggioni3, Fenicia Vescio1, Ranya Al Ameri4, Riccardo De Santis3, Ghada Helaly2, Alice Pomponi3, Alessandra Lo Presti1, Dalia Metwally2, Massimo Fantini5, FV, Hussein Qadi4, Massimo Ciccozzi1, Florigio Lista3 1Department of lnfectious, Parasitic and lmmunomediated Diseases, Istituto Superiore di Sanità, Roma, Italy; 2 Medical Research lnstitute- Alexandria University, Egypt; 3Histology and Molecular Biology Section, Army Medical an d Veterinary Research Center, Roma, ltaly; 4 University of Sana’a, Republic of Yemen; 5Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Roma, ltaly * * Background Fig.1 * * Yemen, which is located in the southwestern end of the Arabian Peninsula, is one of the * countries most affected by recurrent epidemics of dengue. * I We conducted a study on individuals hospitalized with dengue-like syndrome in Al Hodayda, with the aim of identifying viral agents responsible of febrile illness (i.e., dengue [DENV], chikungunya [CHIKV], Rift Valley [RVFV] and hemorrhagic fever virus Alkhurma). * * * Methods * The study site was represented by five hospital centers located in Al-Hodayda, United Republic * of Yemen. Patients were recruited in 2011 and 2012. Serum samples were analysed by ELISA * for the presence of IgM antibody against DENV and CHIKV by using commercial assays. Nucleic * acids were extracted by automated method and analyzed by using specific PCR for the Fig. 2 presence of sequences of DENV, RVF virus, Alkhurma virus and CHIKV. To confirm the results, 15 DENV positive sera underwent specific NS1 gene amplification and sequencing reaction. Similarly, CHIKV positive sera were thoroughly investigated by amplification and sequencing Conclusions the gene encoding the E1 protein.
    [Show full text]
  • Generic Amplification and Next Generation Sequencing Reveal
    Dinçer et al. Parasites & Vectors (2017) 10:335 DOI 10.1186/s13071-017-2279-1 RESEARCH Open Access Generic amplification and next generation sequencing reveal Crimean-Congo hemorrhagic fever virus AP92-like strain and distinct tick phleboviruses in Anatolia, Turkey Ender Dinçer1†, Annika Brinkmann2†, Olcay Hekimoğlu3, Sabri Hacıoğlu4, Katalin Földes4, Zeynep Karapınar5, Pelin Fatoş Polat6, Bekir Oğuz5, Özlem Orunç Kılınç7, Peter Hagedorn2, Nurdan Özer3, Aykut Özkul4, Andreas Nitsche2 and Koray Ergünay2,8* Abstract Background: Ticks are involved with the transmission of several viruses with significant health impact. As incidences of tick-borne viral infections are rising, several novel and divergent tick- associated viruses have recently been documented to exist and circulate worldwide. This study was performed as a cross-sectional screening for all major tick-borne viruses in several regions in Turkey. Next generation sequencing (NGS) was employed for virus genome characterization. Ticks were collected at 43 locations in 14 provinces across the Aegean, Thrace, Mediterranean, Black Sea, central, southern and eastern regions of Anatolia during 2014–2016. Following morphological identification, ticks were pooled and analysed via generic nucleic acid amplification of the viruses belonging to the genera Flavivirus, Nairovirus and Phlebovirus of the families Flaviviridae and Bunyaviridae, followed by sequencing and NGS in selected specimens. Results: A total of 814 specimens, comprising 13 tick species, were collected and evaluated in 187 pools. Nairovirus and phlebovirus assays were positive in 6 (3.2%) and 48 (25.6%) pools. All nairovirus sequences were closely-related to the Crimean-Congo hemorrhagic fever virus (CCHFV) strain AP92 and formed a phylogenetically distinct cluster among related strains.
    [Show full text]
  • Potential Arbovirus Emergence and Implications for the United Kingdom Ernest Andrew Gould,* Stephen Higgs,† Alan Buckley,* and Tamara Sergeevna Gritsun*
    Potential Arbovirus Emergence and Implications for the United Kingdom Ernest Andrew Gould,* Stephen Higgs,† Alan Buckley,* and Tamara Sergeevna Gritsun* Arboviruses have evolved a number of strategies to Chikungunya virus and in the family Bunyaviridae, sand- survive environmental challenges. This review examines fly fever Naples virus (often referred to as Toscana virus), the factors that may determine arbovirus emergence, pro- sandfly fever Sicilian virus, Crimean-Congo hemorrhagic vides examples of arboviruses that have emerged into new fever virus (CCHFV), Inkoo virus, and Tahyna virus, habitats, reviews the arbovirus situation in western Europe which is widespread throughout Europe. Rift Valley fever in detail, discusses potential arthropod vectors, and attempts to predict the risk for arbovirus emergence in the virus (RVFV) and Nairobi sheep disease virus (NSDV) United Kingdom. We conclude that climate change is prob- could be introduced to Europe from Africa through animal ably the most important requirement for the emergence of transportation. Finally, the family Reoviridae contains a arthropodborne diseases such as dengue fever, yellow variety of animal arbovirus pathogens, including blue- fever, Rift Valley fever, Japanese encephalitis, Crimean- tongue virus and African horse sickness virus, both known Congo hemorrhagic fever, bluetongue, and African horse to be circulating in Europe. This review considers whether sickness in the United Kingdom. While other arboviruses, any of these pathogenic arboviruses are likely to emerge such as West Nile virus, Sindbis virus, Tahyna virus, and and cause disease in the United Kingdom in the foresee- Louping ill virus, apparently circulate in the United able future. Kingdom, they do not appear to present an imminent threat to humans or animals.
    [Show full text]
  • Alkhurma Hemorrhagic Fever in Humans, Najran, Saudi Arabia Abdullah G
    RESEARCH Alkhurma Hemorrhagic Fever in Humans, Najran, Saudi Arabia Abdullah G. Alzahrani, Hassan M. Al Shaiban, Mohammad A. Al Mazroa, Osama Al-Hayani, Adam MacNeil, Pierre E. Rollin, and Ziad A. Memish Alkhurma virus is a fl avivirus, discovered in 1994 in a district, south of Jeddah (3). Among the 20 patients with person who died of hemorrhagic fever after slaughtering a confi rmed cases, 11 had hemorrhagic manifestations and sheep from the city of Alkhurma, Saudi Arabia. Since then, 5 died. several cases of Alkhurma hemorrhagic fever (ALKHF), Full genome sequencing has indicated that ALKV is with fatality rates up to 25%, have been documented. From a distinct variant of Kyasanur Forest disease virus, a vi- January 1, 2006, through April 1, 2009, active disease sur- rus endemic to the state of Karnataka, India (4). Recently, veillance and serologic testing of household contacts identi- fi ed ALKHF in 28 persons in Najran, Saudi Arabia. For epi- ALKV was found by reverse transcription–PCR in Orni- demiologic comparison, serologic testing of household and thodoros savignyi ticks collected from camels and camel neighborhood controls identifi ed 65 serologically negative resting places in 3 locations in western Saudi Arabia (5). persons. Among ALKHF patients, 11 were hospitalized and ALKHF is thought to be a zoonotic disease, and reservoir 17 had subclinical infection. Univariate analysis indicated hosts may include camels and sheep. Suggested routes of that the following were associated with Alkhurma virus in- transmission are contamination of a skin wound with blood fection: contact with domestic animals, feeding and slaugh- of an infected vertebrate, bite of an infected tick, or drink- tering animals, handling raw meat products, drinking unpas- ing of unpasteurized, contaminated milk (6).
    [Show full text]
  • Alkhurma Hemorrhagic Fever Virus March 25 Th, 2009
    Department of International & Tropical diseases Alkhurma Hemorrhagic Fever Virus March 25th, 2009 1. ALKHURMA HEMORRHAGIC FEVER • Seasonality: Unknown. Seasonality not excluded VIRUS (AHFV) (see figure 1). To date, available data are insufficient to document it. • Isolated for the first time in 1994 in Alkhumra district (south of Jeddah), Makkah province, Saudi Arabia. Figure 1. Annual distribution of 11 AHFV infections in Saudi Arabia, 1994–1999 (Charrel, Zaki et al., 2005) • Genus: Flavivirus. Genetically very closely related to Kyasanur forest disease (KFD) virus, which circulates in India (Karnataka) and probably in China. • Vector: Ticks, (possible other vectors) Available data are in favour of ticks bite transmission: ° AHFV is genetically and serologically closely related to tick-borne flaviviruses. ° Tick bite has been associated with clinical cases. ° AHFV RNA was recently detected in ticks (Ornithodoros savignyi) collected on a camel resting place in Jeddah. ° O. savignyi were found where AHFV infected cases were reported. The hypothesis that mosquitoes could also be vectors was mentioned in a prospective survey performed in • Incubation period: Unknown. Probably similar to Saudi Arabia. Although this hypothesis cannot be KFD, i.e. 3-8 days. formally excluded, no data were provided to • Clinic: Acute febrile flulike illness with hepatitis substantiate it. (100%), hemorrhagic manifestations (55%), and • Reservoir: Not documented. Probably sheep, camels, encephalitis (20%). The potential existence of pauci- goats. symptomatic and asymptomatic forms is unknown but probable. • Geographical distribution: Unknown. Reported only in Saudi Arabia in Makkah and Najran provinces, both • Lethality: 25-30% of reported cases. located on West coast of the country (Map 1). • Diagnostic: PCR, viral culture and serology (possible Map 1.
    [Show full text]
  • The-Dictionary-Of-Virology-4Th-Mahy
    The Dictionary of VIROLOGY This page intentionally left blank The Dictionary of VIROLOGY Fourth Edition Brian W.J. Mahy Division of Emerging Infections and Surveillance Services Centers for Disease Control and Prevention Atlanta, GA 30333 USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 32 Jamestown Road, London NW1 7BY, UK Copyright © 2009 Elsevier Ltd. All rights reserved No part of this publication may be reproduced, stored in a retrieval system or trans- mitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Departmentin Oxford, UK: phone (ϩ44) (0) 1865 843830; fax (ϩ44) (0) 1865 853333; email: [email protected]. Alternatively visit the Science and Technology website at www.elsevierdirect.com/rights for further information Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloguing in Publication Data A catalogue record for this book is available from the Library of Congress ISBN 978-0-12-373732-8 For information on all Academic Press publications visit our website at www.elsevierdirect.com Typeset by Charon Tec Ltd., A Macmillan Company.
    [Show full text]
  • Construction of an Infectious Cdna Clone for Omsk Hemorrhagic Fever Virus, and Characterization of Mutations in Title NS2A and NS5
    Construction of an infectious cDNA clone for Omsk hemorrhagic fever virus, and characterization of mutations in Title NS2A and NS5 Author(s) Yoshii, Kentaro; Igarashi, Manabu; Ito, Kimihito; Kariwa, Hiroaki; Holbrook, Michael R.; Takashima, Ikuo Virus Research, 155(1), 61-68 Citation https://doi.org/10.1016/j.virusres.2010.08.023 Issue Date 2011-01 Doc URL http://hdl.handle.net/2115/45025 Type article (author version) Additional Information There are other files related to this item in HUSCAP. Check the above URL. File Information VR155-1_61-68.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Construction of an infectious cDNA clone for Omsk Hemorrhagic fever virus, and characterization of mutations in NS2A and NS5 Kentaro Yoshii1, 2, Manabu Igarashi3, Kimihito Ito3, Hiroaki Kariwa1, Michael R Holbrook2, 4, Ikuo Takashima1 1 Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan 2 Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555, US 3 Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan. 4 NIAID Integrated Research Facility, Frederick, MD 21702, US Corresponding author: Dr. Kentaro Yoshii Postal address: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, kita-18 nishi-9, kita-ku, Sapporo, Hokkaido 060-0818, Japan Tel/fax: +81-11-706-5213 E-mail: [email protected] 1 Abstract Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis serocomplex of flaviviruses, and causes hemorrhagic disease in humans.
    [Show full text]
  • Alkhurma Hemorrhagic Fever (AHF)
    Alkhurma Hemorrhagic Fever (AHF) Alkhurma hemorrhagic fever (AHF) is caused by Alkhurma hemorrhagic fever virus (AHFV), a tick-borne virus of the Flavivirus family. The virus was initially isolated in 1995 from a patient in Saudi Arabia. Subsequent cases of AHF have been documented in tourists in Egypt, extending the geographic range of the virus and suggesting that geographic distribution of the virus is wide and that infections due to AHFV are underreported. The persistence of the virus within tick populations, and the role of livestock in the disease transmission process, are not well understood. The AHFV virus is a variant of Kyasanur Forest Disease (KFD), a tick-borne Flavivirus found in Karnataka State and environs in India. Since the first description of AHFV, several hundred cases of AHF have been reported. Cases appear to peak in spring and summer. Further study of AHFV is needed to improve public health measures. Transmission Transmission of AHFV is not well understood. AHFV is a zoonotic virus, and its described tick hosts (the soft tick Ornithodoros savignyi and the hard tick Hyalomma dromedari) are widely distributed. People can become infected through a tick bite or when crushing infected ticks. Epidemiologic studies indicate that contact with domestic animals or livestock may increase the risk of human infection. No human-to-human transmission of AHF has been documented. Although livestock animals may provide blood meals for ticks, it is thought that they play a minor role in transmitting AHFV to humans. No transmission through non-pasteurized milk has been described, although other tick-borne flaviviruses have been transmitted to humans through this route.
    [Show full text]
  • Recent Ancestry of Kyasanur Forest Disease Virus Rajeev Mehla, Sandeep R.P
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Publications of the IAS Fellows Recent Ancestry of Kyasanur Forest Disease Virus Rajeev Mehla, Sandeep R.P. Kumar, Pragya Yadav, Pradip V. Barde, Prasanna N. Yergolkar, Bobbie R. Erickson, Serena A. Carroll, Akhilesh C. Mishra, Stuart T. Nichol, and Devendra T. Mourya Kyasanur Forest disease virus (KFDV) is enzootic to In- as Presbytis entellus) and the red-faced bonnet monkey dia and maintained in ticks, mammals, and birds. It causes (Macaca radiata). severe febrile illness in humans and was first recognized Human cases were also found among persons who in 1957 associated with a high number of deaths among visited forests to collect firewood, grass, and other forest monkeys in Kyasanur Forest. Genetic analysis of 48 virus- products. Human disease is characterized by an incubation es isolated in India during 1957–2006 showed low diversity period of ≈3–8 days, followed by chills, frontal headache, (1.2%). Bayesian coalescence analysis of these sequences and those of KFDVs from Saudi Arabia and the People’s body ache, and high fever for 5–12 days, and a case-fatality Republic of China estimated that KFDVs have evolved at rate >30% (2). During infection by KFDV, virus titer re- a mean rate of ≈6.4 × 10–4 substitutions/site/year, which is mains high <10 days after onset of symptoms, as reported similar to rates estimated for mosquito-borne flaviviruses. by Bhat et al. (3). However, Upadhyaya et al. (4) found KFDVs were estimated to have shared a common ancestor that viremia in patients lasted for 12–13 days of illness and in ≈1942, fifteen years before identification of the disease in unlike most other flaviviruses, remains high during the first India.
    [Show full text]
  • Alkhumra Hemorrhagic Fever in Saudi Arabia: Review Article
    3 | P a g e Review Article Alkhumra Hemorrhagic Fever in Saudi Arabia KAZI AMINUL ISLAM1,2 ABSTRACT 1 Department of Medical Education, College of Dentistry, Taibah University, Al 2 Madinah Al Munawarah, KSA; Miqat General Hospital, Al Madinah Al Objective: Alkhumra virus (ALKV) was identified in Munawarah, KSA 1994 as the agent of a hemorrhagic fever in Saudi Ara- bia. Genetic and phylogenetic analyses characterize it Received 18 November 2017 as a variant genotype of Kyasanur Forest disease virus Accepted 14 December 2017 (KFDV). Since then, several cases of Alkhumra hem- orrhagic fever (ALKHF) with fatality rates as high as Introduction 25% have been documented in Saudi Arabia. The aim Alkhumra hemorrhagic fever (ALKHF) acquired its name of the current article is to review and provide an insight into ALKHF in Saudi Arabia. from the town of Alkhumra near Taif, east of Jeddah, Saudi Methods: Articles published between 1994 and 2014 Arabia, where the first case was discovered in 1994-1995 on ALKV and ALKHF were studied by reviewing the Medline/PubMed databases - the online Google [1,2]. After that, it was detected in Makkah in 2001-2003. Scholar database and the ProMED database using the The new hemorrhagic fever virus (Alkhumra virus), was keywords Alkhumra virus, Alkhumra Hemorrhagic fe- misnamed as Alkhurma virus but was then recognized by ver, Kyasanur Forest disease virus, Viral hemorrhagic fever, Zoonotic disease. the International Committee on Taxonomy of Viruses Results: ALKV is a tick-borne flavivirus that causes (ICTV) as Alkhumra virus [3-5]. Subsequently it was re- hemorrhagic fever in humans.
    [Show full text]
  • Emergence of Viral Diseases in the Asia-Pacific Region
    Emerging zoonoses in the Asian‐ Pacific region John S Mackenzie Faculty of Health Sciences, Curtin University, and Burnet Institute, Melbourne …in the context of emerging/epidemic disease at the beginning of the 21st. Century: Emergence of new or newly recognised pathogens (e.g. Highly Pathogenic Avian Influenza [H5N1], swine influenza H1N1, SARS, Nipah virus, swine infections with Ebola-Reston virus) Resurgence of well characterised outbreak- prone diseases (e.g. dengue, measles, yellow fever, chikungunya, cholera, TB, meningitis, shigellosis, etc) Concern about accidental or deliberate release of a biological agent (e.g. smallpox, SARS, Ebola, anthrax, tularaemia) There can be huge economic costs due to infectious disease outbreaks (e.g. >US$60 billion for SARS). Many of the current threats are zoonoses, and they are usually the diseases which cost us most! Challenges: Economic Impact of Emerging Infectious Disease 3 Emerging diseases: the definition • New diseases which have not been recognised previously. • Known diseases which are increasing, or threaten to increase, in incidence or in geographic distribution. • The terms ‘re‐emerging or resurgent diseases’ are also used – usually to describe diseases which we had thought had been controlled by immunisation, antibiotic use or environmental changes, but which are now reappearing. ‐So, to the questions: ‐ How and from where do novel or emergent viruses arise or expand? ‐ What factors precipitate their emergence and spread? ‐ What messages can we take home from specific examples of emerging diseases? ‐ Can we predict where the next emergent disease will occur? How and where do novel or emergent viral diseases arise? Most emergent viruses have been around for many years or even millennia.
    [Show full text]