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California Encephalitis Orthobunyaviruses in Northern Europe

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California Encephalitis Orthobunyaviruses in Northern Europe California encephalitis orthobunyaviruses in northern Europe NIINA PUTKURI Department of Virology Faculty of Medicine, University of Helsinki Doctoral Program in Biomedicine Doctoral School in Health Sciences Academic Dissertation To be presented for public examination with the permission of the Faculty of Medicine, University of Helsinki, in lecture hall 13 at the Main Building, Fabianinkatu 33, Helsinki, 23rd September 2016 at 12 noon. Helsinki 2016 Supervisors Professor Olli Vapalahti Department of Virology and Veterinary Biosciences, Faculty of Medicine and Veterinary Medicine, University of Helsinki and Department of Virology and Immunology, Hospital District of Helsinki and Uusimaa, Helsinki, Finland Professor Antti Vaheri Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland Reviewers Docent Heli Harvala Simmonds Unit for Laboratory surveillance of vaccine preventable diseases, Public Health Agency of Sweden, Solna, Sweden and European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden Docent Pamela Österlund Viral Infections Unit, National Institute for Health and Welfare, Helsinki, Finland Offical Opponent Professor Jonas Schmidt-Chanasit Bernhard Nocht Institute for Tropical Medicine WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research National Reference Centre for Tropical Infectious Disease Hamburg, Germany ISBN 978-951-51-2399-2 (PRINT) ISBN 978-951-51-2400-5 (PDF, available at http://ethesis.helsinki.fi) Unigrafia, Helsinki, Finland 2016 It is better to understand a little than to misunderstand a lot -Anatole France Table of Contents TABLE OF CONTENTS .................................................................................................................... 4 LIST OF ORIGINAL PUBLICATIONS ................................................................................................. 6 LIST OF ABBREVIATIONS ............................................................................................................... 7 ABSTRACT ..................................................................................................................................... 8 REVIEW OF THE LITERATURE ...................................................................................................... 10 1 INTRODUCTION .................................................................................................................. 10 1.1 CALIFORNIA SEROGROUP ........................................................................................................10 1.2 ARTHROPODS AND INFECTIOUS DISEASES....................................................................................10 2 FAMILY BUNYAVIRIDAE ...................................................................................................... 12 3 GENUS ORTHOBUNYAVIRUS .............................................................................................. 14 3.1 GEOGRAPHICAL DISTRIBUTION AND RESERVOIR HOSTS ..................................................................14 3.2 ORTHOBUNYAVIRUS DISEASE ASSOCIATIONS IN HUMANS AND ANIMALS ............................................16 3.3 MOLECULAR BIOLOGY OF ORTHOBUNYAVIRUSES ..........................................................................18 3.4 GENETIC REASSORTMENT ........................................................................................................20 3.5 ORTHOBUNYAVIRUSES IN EUROPE ............................................................................................21 4 CALIFORNIA SEROGROUP (CALIFORNIA ENCEPHALITIS VIRUS GROUP, CEV GROUP) .......... 22 4.1 MEMBERS OF THE CEV GROUP ................................................................................................22 4.2 TRANSMISSION CYCLE OF THE CEV GROUP .................................................................................26 4.3 CEV REPLICATION .................................................................................................................29 4.4 CEV PATHOGENICITY .............................................................................................................30 4.5 CLINICAL DISEASE IN HUMANS ..................................................................................................31 4.6 CALIFORNIA SEROGROUP VIRUSES IN NORTHERN EUROPE ..............................................................33 4.7 DIAGNOSTIC METHODS FOR CEV INFECTIONS ..............................................................................34 5 AIM OF THE STUDY ............................................................................................................. 35 6 MATERIALS AND METHODS................................................................................................ 36 6.1 SAMPLES .............................................................................................................................36 6.1.1 Patient serum samples (original publications I, III, IV) .................................................36 6.1.2 Mosquitoes (original publication II) .............................................................................36 6.2 SEROLOGICAL METHODS (ORIGINAL PUBLICATIONS I, III AND IV) .....................................................37 6.3 VIRUS ISOLATION ATTEMPTS (ORIGINAL PUBLICATIONS II AND III) ...................................................38 6.4 MOLECULAR METHODS...........................................................................................................39 6.4.1 PCR methods for screening (original publications II and III) ........................................39 6.4.2 Sequencing (original publication II) ..............................................................................39 6.4.3 Genomic and phylogenetic analysis (original publication II) ........................................39 6.5 VIRAL PROTEIN EXPRESSION AND METABOLIC LABELLING (ORIGINAL PUBLICATION I) ............................40 7 RESULTS AND DISCUSSION ................................................................................................. 40 7.1 SERODIAGNOSTICS .................................................................................................................40 7.1.1 IgG and IgM IFA test for detecting California encephalitis virus infections (I) .............40 4 7.1.2 Antibody response in INKV infection (I) ........................................................................41 7.1.3 Seroprevalence of INKV infection in humans (I, IV) ......................................................43 7.2 NEW CALIFORNIA SEROGROUP VIRUSES IN FINLAND (II) ................................................................45 7.3 INKV AND CHATV INFECTIONS IN HUMANS (III) .........................................................................52 7.3.1 Frequency of acute infections in humans .....................................................................52 7.3.2 Clinical characteristics of the acute disease in humans ...............................................55 8 CONCLUDING REMARKS AND FUTURE PROSPECTS ............................................................. 57 ACKNOWLEDGEMENTS ............................................................................................................... 58 REFERENCES ............................................................................................................................... 60 APPENDIX 1 ................................................................................................................................ 86 ORIGINAL PUBLICATIONS ........................................................................................................... 98 5 List of original publications This thesis is based on the following articles, which are referred in the text by Roman numerals (I-IV). I. Putkuri, N., Vaheri, A. and Vapalahti, O. 2007. Prevalence and protein specificity of human antibodies to Inkoo virus infection. Clinical and Vaccine Immunology, 14(12), 1555-62. II. Putkuri, N., Kurkela, S., Levanov, L., Huhtamo, E., Vaheri, A. Sironen, T. and Vapalahti, O. 2014. Isolation and characterization of a California encephalitis serogroup orthobunyavirus from Finnish mosquitoes. Infection, Genetics and Evolution. Mar; 22:164-73. III. Putkuri, N., Kantele, A., Levanov, L., Brummer-Korvenkontio, M., Vaheri, A. and Vapalahti, O. 2016. Acute human Inkoo and Chatanga virus infections, Finland. Emerging Infectious Disease. May;22(5):810-7. IV. Evander, M., Putkuri, N., Eliasson, M., Vapalahti, O. and Ahlm, C. 2016. Seroprevalence and risk factors for Inkoo virus in Northern Sweden. American Journal of Tropical Medicine and Hygiene. May 4;94(5):1103-6. 6 List of abbreviations CNS central nervous system CPE cytopathogenic effect Cx. Culex EIA enzyme immunoassay ELISA enzyme-linked immunosorbent assay Gc protein carboxy-terminal glycoprotein Gn protein amino-terminal glycoprotein HI hemagglutination inhibition test ICTV International Committee on Taxonomy of Viruses IFA indirect immunofluorescence assay IgG immunoglobulin G IgM immunoglobulin M kb kilobase kDa kilodalton L protein large segment coded RNA-dependent RNA polymerase N protein nucleocapsid protein NSm non-structural protein, M segment NSs non-structural protein, S segment PRNT50 plaque reduction neutralization assay (50% reduction) Och. Ochlerotatus RdRp RNA-dependent RNA polymerase RNAi RNA interference RNP ribonucleoprotein All the abbreviations for virus
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