Yliopiston etusivulle Suomeksi På svenska In English Helsingin yliopisto

Genetic characterisation of field and attenuated rabies viruses and molecular epidemiology of rabies in Finland and Russia

Show simple item record

dc.contributor University of Helsinki, Faculty of Veterinary Medicine, Department of Basic Veterinary Sciences, Pathology en
dc.contributor Helsingin yliopisto, eläinlääketieteellinen tiedekunta, peruseläinlääketieteen laitos fi
dc.contributor Helsingfors universitet, veterinärmedicinska fakulteten, institutionen för basveterinärmedicin sv
dc.contributor.author Metlin, Artem fi
dc.date.accessioned 2010-11-25T09:09:57Z
dc.date.available 2010-11-25T09:09:57Z
dc.date.issued 2008-01-28 fi
dc.identifier.uri URN:ISBN:978-952-225-002-5 fi
dc.identifier.uri http://hdl.handle.net/10138/18951
dc.description.abstract Rabies is a fatal disease that affects the central nervous system of all warmblooded mammals. The rabies virus belongs to the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus. This virus has a negative single-stranded RNA genome and the virions are bullet-shaped. Rabies is reported in many countries throughout the world and has been registered in all continents except Australia, where only the bat Lyssaviruses have been found, and in Antarctica where the main vectors of rabies are absent. Russia and most of the bordering countries are affected by rabies. Finland was a rabies-free country from 1959 to 1988, when a sylvatic rabies epidemic appeared with raccoon dogs as the main host and vector of infection. That epidemic was eradicated by the oral vaccination of wild carnivores and the parenteral immunization of dogs and cats; and Finland has been rabies-free since 1991. However, this status is constantly under threat because rabies is endemic in Russia and Estonia. In June 2003, a horse imported to Finland from Estonia was clinically and laboratory diagnosed as rabies positive. The close relationship of the isolated equine virus strain with the current Estonian strains was verified during subsequent molecular epidemiological studies. Because the case was imported, it did not affect Finland’s rabies-free status. Also in 2007 another 2 imported cases of rabies were recorded: one in a human being from Philippines and the other in a dog from India. Five different antigenic variants of the rabies virus were identified among rabies positive field samples from Russia, Finland, and Estonia by using antinucleocapsid monoclonal antibodies. Two rabies virus field isolates showed a different reaction pattern that was similar to that of the vaccine strains of the SAD group, which might suggest a new antigen variant or reverted vaccine strain. Nevertheless, the sequence analysis showed that the vaccine strains RV-97 and SAD B19 included in the oral anti-rabies vaccine “Sinrab” (Russia) and “Fuchsoral” (Germany), respectively, differ considerably from all the field strains. Field rabies viruses collected in recent years from different regions of the Russian Federation were chosen on the basis of mAb studies and geographical origin for molecular epidemiological studies to characterize their genetic heterogeneity and to study their molecular epidemiology. In addition to the Russian viruses, archival samples from Estonia and Finland and Russian vaccine strains were also included in this study. Among the field viruses studied, two main phylogenetic groups were found, and designated as the Pan-Eurasian and Caucasian based on their geographical origin. The Pan-Eurasian 7 group including some reference viruses from Europe was further divided into four subgroups. All the vaccine strains were clearly different from the field strains. No recombination between the field and vaccine virus strains was observed. The critical roles of geographical isolation, the limitation of the genetic clustering, and the evolution of the rabies virus were shown during this study. The rabies virus vaccine strain RV-97 is widely used in Russia as a component of the oral anti-rabies vaccine “Sinrab”. To characterize the molecular properties of this strain, entire genome sequencing was conducted. A simple technique was developed to obtain this sequence, including the 3’- and 5’- ends. The entire genome sequence and deduced amino-acid sequences of the major viral proteins were compared with the sequences of other known fixed rabies viruses. The strain RV-97 formed a separate phylogenetic branch and seems to be more related to the group of Japanese strains. The field strains from the Caucasian group seem to be phylogenetically the nearest group to the RV-97 strain. The data shown herein makes it possible to develop molecular methods for distinguishing between the field rabies viruses from the vaccine strains for the rapid recognition of the vaccine strains that are unstable or have reverted back to their pathogenic form. The wide genetic heterogeneity verified in this study indicates that it is important to remain on permanent alert for the appearance of rabies. fi
dc.description.abstract Rabies is a fatal disease that affects the central nervous system of all warmblooded mammals. The rabies virus belongs to the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus. This virus has a negative single-stranded RNA genome and the virions are bullet-shaped. Rabies is reported in many countries throughout the world and has been registered in all continents except Australia, where only the bat Lyssaviruses have been found, and in Antarctica where the main vectors of rabies are absent. Russia and most of the bordering countries are affected by rabies. Finland was a rabies-free country from 1959 to 1988, when a sylvatic rabies epidemic appeared with raccoon dogs as the main host and vector of infection. That epidemic was eradicated by the oral vaccination of wild carnivores and the parenteral immunization of dogs and cats; and Finland has been rabies-free since 1991. However, this status is constantly under threat because rabies is endemic in Russia and Estonia. In June 2003, a horse imported to Finland from Estonia was clinically and laboratory diagnosed as rabies positive. The close relationship of the isolated equine virus strain with the current Estonian strains was verified during subsequent molecular epidemiological studies. Because the case was imported, it did not affect Finland’s rabies-free status. Also in 2007 another 2 imported cases of rabies were recorded: one in a human being from Philippines and the other in a dog from India. Five different antigenic variants of the rabies virus were identified among rabies positive field samples from Russia, Finland, and Estonia by using antinucleocapsid monoclonal antibodies. Two rabies virus field isolates showed a different reaction pattern that was similar to that of the vaccine strains of the SAD group, which might suggest a new antigen variant or reverted vaccine strain. Nevertheless, the sequence analysis showed that the vaccine strains RV-97 and SAD B19 included in the oral anti-rabies vaccine “Sinrab” (Russia) and “Fuchsoral” (Germany), respectively, differ considerably from all the field strains. Field rabies viruses collected in recent years from different regions of the Russian Federation were chosen on the basis of mAb studies and geographical origin for molecular epidemiological studies to characterize their genetic heterogeneity and to study their molecular epidemiology. In addition to the Russian viruses, archival samples from Estonia and Finland and Russian vaccine strains were also included in this study. Among the field viruses studied, two main phylogenetic groups were found, and designated as the Pan-Eurasian and Caucasian based on their geographical origin. The Pan-Eurasian 7 group including some reference viruses from Europe was further divided into four subgroups. All the vaccine strains were clearly different from the field strains. No recombination between the field and vaccine virus strains was observed. The critical roles of geographical isolation, the limitation of the genetic clustering, and the evolution of the rabies virus were shown during this study. The rabies virus vaccine strain RV-97 is widely used in Russia as a component of the oral anti-rabies vaccine “Sinrab”. To characterize the molecular properties of this strain, entire genome sequencing was conducted. A simple technique was developed to obtain this sequence, including the 3’- and 5’- ends. The entire genome sequence and deduced amino-acid sequences of the major viral proteins were compared with the sequences of other known fixed rabies viruses. The strain RV-97 formed a separate phylogenetic branch and seems to be more related to the group of Japanese strains. The field strains from the Caucasian group seem to be phylogenetically the nearest group to the RV-97 strain. The data shown herein makes it possible to develop molecular methods for distinguishing between the field rabies viruses from the vaccine strains for the rapid recognition of the vaccine strains that are unstable or have reverted back to their pathogenic form. The wide genetic heterogeneity verified in this study indicates that it is important to remain on permanent alert for the appearance of rabies. en
dc.language.iso en fi
dc.publisher Helsinki University Printing House fi
dc.relation.ispartof URN:ISSN:1796-4660 fi
dc.relation.ispartof Evira Research Reports fi
dc.rights Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. sv
dc.rights Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. fi
dc.rights This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. en
dc.subject veterinary Medicine fi
dc.title Genetic characterisation of field and attenuated rabies viruses and molecular epidemiology of rabies in Finland and Russia en
dc.type.ontasot Doctoral dissertation (article-based) en
dc.type.ontasot Väitöskirja (artikkeli) fi
dc.type.ontasot Doktorsavhandling (sammanläggning) sv
dc.ths Huovilainen, Anita fi
dc.ths Vapalahti, Olli fi
dc.opn Tordo, Noel fi
dc.type.dcmitype Text fi

Files in this item

Files Size Format View/Open
geneticc.pdf 726.2Kb PDF View/Open
This item appears in the following Collection(s)

Show simple item record

Search Helda


Advanced Search

Browse

My Account