Rhabdoviridae

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Overview of rhabdoviridae

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Rhabdoviridae

  1. 1. Rhabdoviridae Brian Wells
  2. 2. Introduction <ul><li>Encompasses > 150 viruses </li></ul><ul><li>Rabies – only important human pathogen </li></ul><ul><li>One of the most lethal of all infectious diseases </li></ul>
  3. 3. History <ul><li>Adapted from Latin meaning “to rage” </li></ul><ul><li>Greeks – lyssa – “frenzy” </li></ul><ul><li>Rabies represents one of the oldest and most feared diseases </li></ul><ul><li>Recognized in Egypt before 2300 B.C. </li></ul><ul><li>Well described by Aristotle </li></ul><ul><li>Iliad – “canine madness” </li></ul>
  4. 4. History <ul><li>1885 – Louis Pasteur – rabies vaccine </li></ul><ul><ul><li>Attenuated form of virus produced by inoculation of rabbit spinal cord </li></ul></ul><ul><li>Occurs throughout the world except in Australia, Japan, Great Britain, and islands such as Hawaii </li></ul><ul><li>“Reportable” disease </li></ul>
  5. 5. Taxonomy <ul><li>3 Genera – Ephemerovirus, Lyssavirus, Vesiculovirus </li></ul><ul><li>Infect vertebrates, invertebrates, and plants </li></ul><ul><li>Genus Lyssavirus comprises rabies virus and 3 rabies-like viruses </li></ul><ul><li>Each capable of causing rabies-like disease in humans </li></ul>
  6. 6. Viral Structure <ul><li>170 nm x 70 nm </li></ul><ul><li>Bullet-shaped enveloped virion </li></ul><ul><ul><li>Glycoprotein peplomers & matrix protein under envelope </li></ul></ul><ul><li>Helical symmetry </li></ul><ul><li>Linear minus sense ssRNA – 11-12 kb </li></ul><ul><li>Glycoprotein spikes in outer membrane bilayer </li></ul>
  7. 8. Virus Replication <ul><li>Receptor-mediated endocytosis </li></ul><ul><li>Uncoat and release nucleocapsid into cytoplasm </li></ul><ul><li>Production of 5 monocistronic mRNA species - N, P (NS), M, G, L – by L+P viral transcriptase </li></ul><ul><li>Each mRNA capped and poly-A’ed </li></ul><ul><li>dsRNA replicative intermediate </li></ul>
  8. 9. Virus Replication
  9. 10. Virus Replication <ul><li>N+P+L and (-) ssRNA form core </li></ul><ul><li>M forms matrix around core </li></ul><ul><li>Virus buds from glycoprotein area of plasma membrane and thus acquires its envelope </li></ul>
  10. 12. Transmission <ul><li>Unstable in the environment </li></ul><ul><li>Mostly transmitted via bite or scratch from infected animal </li></ul><ul><li>Can be transmitted via aerosol in places with high virus levels (bat caves) </li></ul><ul><li>Also transmitted iatrogenically via corneal transplant </li></ul>
  11. 15. Epidemiology <ul><li>Rabies-free countries </li></ul><ul><ul><li>Eradicated twice in UK (1902 and 1922) </li></ul></ul><ul><li>Developing countries </li></ul><ul><ul><li>Enzootic dog rabies represents a serious problem </li></ul></ul><ul><ul><li>Need for stray dog and cat population control and immunization, accurate incidence data, surveillance, and public education programs </li></ul></ul>
  12. 16. Epidemiology <ul><li>Vaccination of animals has reduced transmission rate </li></ul><ul><ul><li>18,000 receive preexposure prophylaxis </li></ul></ul><ul><ul><li>40,000 receive postexposure prophylaxis </li></ul></ul><ul><ul><li>Approx 1 case of human rabies per year in U.S. </li></ul></ul><ul><li>India records 25,000 human cases annually mainly from dog bites </li></ul>
  13. 18. Epidemiology <ul><li>Zoonotic infection </li></ul><ul><li>As humans as concerned, the dog is the most important reservoir </li></ul><ul><li>Skunks, raccoons, bat, and foxes also reservoirs </li></ul>
  14. 19. Clinical features <ul><li>Incubation/prodrome </li></ul><ul><ul><li>Usually 14 to 90 days but can be far longer </li></ul></ul><ul><ul><li>Pain/itching at site of wound </li></ul></ul><ul><ul><li>Fever, headache, gastrointestinal problems </li></ul></ul><ul><li>After incubation </li></ul><ul><ul><li>CNS effects, hydrophobia from fear of pain associated with drinking </li></ul></ul><ul><ul><li>Seizures and hallucinations </li></ul></ul><ul><li>Following neurological phase, patient becomes comatose </li></ul><ul><li>Respiratory paralysis and death </li></ul>
  15. 20. Diagnosis <ul><li>Overt symptoms define rabies but by this time therapeutic intervention is too late </li></ul><ul><li>Lab tests of animal can ascertain presence of rabies </li></ul><ul><li>Antemortem diagnosis in humans – immunofluorescene or PCT assay on skin biopsy, corneal impression, or saliva </li></ul><ul><li>dFA test most frequently used </li></ul><ul><li>Negri bodies are histologically characteristic </li></ul>
  16. 23. Treatment <ul><li>HDCV rabies vaccine </li></ul><ul><li>Through cleansing of wound </li></ul><ul><li>Postexposure vaccination </li></ul><ul><ul><li>Infecting event is recognizable and incubation period is long </li></ul></ul><ul><ul><li>Regularly and successfully practiced </li></ul></ul><ul><li>Administration of rabies immune globulin IM and around bite. </li></ul><ul><li>Reduce mortality from 100% => 0% </li></ul>
  17. 24. Summary <ul><li>Virus is enveloped with linear (-) ssRNA </li></ul><ul><li>Transmitted via animal bite (saliva), aerosol, and corneal transplant </li></ul><ul><li>Negri bodies are histologically characteristic </li></ul><ul><li>100% mortality from untreated rabies </li></ul><ul><li>Incubation typically 14 – 90 days </li></ul>
  18. 25. Sources <ul><li>http://www.fda.gov/bbs/topics/CONSUMER/CON00053.html </li></ul><ul><li>http://www.stanford.edu/group/virus/rhabdo/rhabdoviridae.html </li></ul><ul><li>http://www.med.sc.edu:85/virol/rabies.htm </li></ul><ul><li>http://www.health.ufl.edu/anires/Rabies/tsld001.htm </li></ul><ul><li>http://www.cdc.gov/ncidod/dvrd/rabies/diagnosis/diagnosi.htm </li></ul>

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