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Genetic characteristics of field and attenuated rabies viruses ... - Evira

Genetic characteristics of field and attenuated rabies viruses ... - Evira

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Content<br />

List <strong>of</strong> abbreviations ....................................................................................................... 5<br />

Abstract............................................................................................................................ 6<br />

List <strong>of</strong> original publications............................................................................................ 8<br />

1. Literature review........................................................................................................ 9<br />

1.2. Rabies virus <strong>characteristics</strong> ................................................................................ 9<br />

1.2.1. Classification ................................................................................................... 9<br />

1.2.2. Structure <strong>of</strong> virion, genome, <strong>and</strong> proteins <strong>of</strong> <strong>rabies</strong> virus............................... 10<br />

1.3. Virus-host interaction ........................................................................................ 12<br />

1.3.1. Pathogenesis................................................................................................. 12<br />

1.3.2. Clinical signs.................................................................................................. 13<br />

1.3.3. Pathological changes .................................................................................... 15<br />

1.4. Laboratory diagnosis <strong>of</strong> <strong>rabies</strong> .......................................................................... 17<br />

1.4.1. Detection <strong>of</strong> viral antigen ............................................................................... 17<br />

1.4.2. Detection <strong>of</strong> viral genome.............................................................................. 18<br />

1.4.3. Virus isolation ................................................................................................ 19<br />

1.4.4. Detection <strong>of</strong> virus neutralizing antibodies ...................................................... 19<br />

1.5. Rabies epidemiology......................................................................................... 21<br />

1.5.1. Rabies situation world-wide........................................................................... 21<br />

1.5.2. Rabies situation in Europe <strong>and</strong> in Russia ...................................................... 22<br />

1.5.3. Models <strong>of</strong> <strong>rabies</strong> epidemics ........................................................................... 24<br />

1.6. Fixed strains <strong>of</strong> <strong>rabies</strong> virus .............................................................................. 25<br />

1.6.1. Laboratory strains.......................................................................................... 25<br />

1.6.2. Vaccine strains <strong>and</strong> anti-<strong>rabies</strong> vaccines....................................................... 25<br />

1.7. Molecular biology <strong>of</strong> <strong>rabies</strong> <strong>viruses</strong> ................................................................... 30<br />

1.7.1. Antigenic characterization with monoclonal antibodies.................................. 30<br />

1.7.2. <strong>Genetic</strong> characterization <strong>of</strong> <strong>rabies</strong> virus......................................................... 31<br />

1.7.3. Entire genome sequencing <strong>of</strong> vaccine strains ............................................... 33<br />

2. Aims <strong>of</strong> the study .................................................................................................... 35<br />

3. Materials <strong>and</strong> methods............................................................................................ 36<br />

3.1. Field <strong>rabies</strong> virus isolates.................................................................................. 36<br />

3.2. Vaccine <strong>and</strong> laboratory strains.......................................................................... 36<br />

3.3. Cell cultures ...................................................................................................... 36<br />

3.4. Monoclonal antibodies ...................................................................................... 37<br />

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