Rabdo Rota Virus

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Rabdo Rota Virus

  1. 1. Rhabdoviruses and reoviruses Rabies and rotavirus www.freelivedoctor.com
  2. 2. Rhabdoviruses Rabies www.freelivedoctor.com
  3. 3. Rabies in the US Distribution of rabies in the US, 2001. (From http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm) www.freelivedoctor.com
  4. 4. Human pathogens in the order Mononegavirales www.freelivedoctor.com Family Subfamily Genus Human pathogens Rhabdoviridae Lyssavirus Rabies virus Filoviridae Marburghvirus Marburgh virus Ebolavirus Ebola virus Paramyxoviridae Paramyxovirinae Rubulavirus Mumps virus, Parainfluenzavirus 2,4 Respirovirus Parainfluenza virus 1,3 Henipavirus Hendra virus, Nipah virus Morbillivirus Measles virus Pneumovirinae Pneumovirus Respiratory syncytial virus Metaneumovirus Human metapneumovirus
  5. 5. Mononegavirales genome structure Paramyxoviridae Rhabdoviridae <ul><li>Notes: </li></ul><ul><li>HN = mumps, PIV; H = measles; G = RSV ,hMPV, rabies </li></ul><ul><li>Rabies lacks F </li></ul><ul><li>P encodes 2-3 proteins in Paramyxovirinae (P/V/C) </li></ul><ul><li>Rubula- , Pneumo- , and Metapneumo- contain extra genes (M2, SH) </li></ul><ul><li>F & G switched in Pneumoviruses </li></ul>www.freelivedoctor.com N P M F H/HN/G L 3’ 5’ N P M G L 3’ 5’
  6. 6. Rhabdovirus gene function www.freelivedoctor.com Gene product Virion location Function Nucleoprotein (N) Nucleocapsid Protects RNA genome Polymerase phosphoprotein (P) Associated with nucleocapsid RNA polymerase subunit Matrix (M) Between nucleocapsid and envelope Virion assembly glycoprotein (G) Transmembrane envelope glycoprotein Viral attachment protein Large protein (L) Associated with nucleocapsid RNA polymerase
  7. 7. Rhabdovirus virion structure A: Diagram of rhabdovirus virion. B: Negative stain electron micrograph of vesicular stomatitis virus (VSV) virion. C: VSV nucleocapsid-M protein complexes prepared by solubilization of virion envelopes with triton X-100 in low ionic strength buffer. D: VSV nucleocapsids prepared by solubilization of virion envelopes with triton X-100 in high ionic strength buffer. Bar, 100 nm. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Fig. 39.2) www.freelivedoctor.com
  8. 8. Rhabdovirus replication Replication of rhabdoviruses: a simple enveloped (-) RNA virus. 1, Rhabdoviruses bind to the cell surface and are ( 2 ) endocytosed. The envelope fuses with the endosome vesicle membrane to deliver the nucleocapsid to the cytoplasm. The virion must carry a polymerase, which ( 3 ) produces five individual messenger RNAs (mRNAs) and a full-length (+) RNA template. 4, Proteins are translated from the mRNAs, including one glycoprotein (G), which is co-translationally glycosylated in the endoplasmic reticulum (ER), processed in the Golgi apparatus, and delivered to the cell membrane. 5, The genome is replicated from the (+) RNA template, and N, L, and NS proteins associate with the genome to form the nucleocapsid. 6, The matrix protein associates with the G protein-modified membrane, which is followed by assembly of the nucleocapsid. 7, The virus buds from the cell in a bullet-shaped virion. (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-14.) www.freelivedoctor.com
  9. 9. Rabies distribution Distribution of animal rabies in the United States, 1999. The percentages relate to the total number of cases of animal rabies. (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 61-3.) Note: Dogs are the primary source of human rabies in urban settings worldwide. www.freelivedoctor.com
  10. 10. Rabies pathogenesis Pathogenesis of rabies virus infection. Numbered steps describe the sequence of events. (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 61-2.) www.freelivedoctor.com
  11. 11. Rabies disease time course Progression of rabies disease. (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Table 61-1.) www.freelivedoctor.com
  12. 12. Rabies treatment <ul><li>Wash wound with soap </li></ul><ul><li>Inject human antirabies IgG into wound </li></ul><ul><li>Vaccination on days 0, 3, 7, 28 post exposure </li></ul><ul><li>Determine if animal is rabid </li></ul>www.freelivedoctor.com
  13. 13. Negri bodies Immunohistochemical staining of intra-cytoplasmic viral inclusions in the neuron of a human rabies patient. (Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Fig. 39.9) www.freelivedoctor.com
  14. 14. Control of rabies in wild animals through bait based vaccination The bait Lunch time http://www.cdc.gov/ncidod/dvrd/rabies/prevention&control/ovalvacc.htm www.freelivedoctor.com
  15. 15. <ul><li>Structure </li></ul><ul><ul><li>Negative sense ssRNA, helical nucleocapsid, envelope </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Transmitted by bite of rabid animal </li></ul></ul><ul><ul><li>Replication in cytoplasm; budding </li></ul></ul><ul><ul><li>Spread by axonal transport to brain; long incubation period </li></ul></ul><ul><ul><li>Fever, nausea, hydrophobia, coma </li></ul></ul><ul><ul><li>Almost always fatal </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Viral antigen or nucleic acid, Negri bodies </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>Inactivated viral vaccine for humans after exposure, live virus vaccine for animals </li></ul></ul>Rabies summary www.freelivedoctor.com
  16. 16. Reoviruses Rotavirus www.freelivedoctor.com
  17. 17. Rotavirus disease burden Annual burden of rotavirus disease worldwide and in the United States in infants and young children under 5 years of age. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Fig. 53.sup8) www.freelivedoctor.com
  18. 18. Rotavirus disease distribution Distribution of rotavirus disease-associated deaths worldwide by region. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia Fig. 53.sup9) www.freelivedoctor.com
  19. 19. Human reoviruses Reoviridae responsible for human disease (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Table 62-1) www.freelivedoctor.com
  20. 20. Rotavirus structure Genome Segments: Shows PAGE separation of the 11 segments of the rotavirus SA11 genome. Encoded proteins: Shows the PAGE separation of the intracellular proteins synthesized by SA11 and the genome segment in which they are encoded. Six structural (VP) and six nonstructural (NSP) proteins are synthesized in the infected cell. Note that NSP6 runs far below NSP5 and is not shown on the gel presented here. Viron Schematic: Shows the locations of the various structural proteins within the rotavirus virion. Note the arrangement of the proteins into 3 concentric capsid layers, and the location of the VP1/VP3 complexes at the 5-fold verticies of the icosahedral structure. Reconstruction: A 3D reconstruction of the SA11 virion (23Å resolution) with the genome computationally removed. The color scheme is the same as the schematic, to indicate locations of the various proteins. (http://www.iah.bbsrc.ac.uk/dsRNA_virus_proteins/rotavirus%20figure.htm) www.freelivedoctor.com
  21. 21. Rotavirus gene function Functions of rotavirus gene products. (From Medical Microbiology, 5 th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Table 62-3) www.freelivedoctor.com
  22. 22. Rotavirus structure Electron micrograph of negatively stained rotavirus virus particles. (From Schaechter’s Mechanisms of Microbial Disease; 4 th ed.; Engleberg, DiRita & Dermody; Lippincott, Williams & Wilkins; 2007; Fig. 37-1) www.freelivedoctor.com
  23. 23. Rotavirus replication The rotavirus replication cycle . (From Schaechter’s Mechanisms of Microbial Disease; 4 th ed.; Engleberg, DiRita & Dermody; Lippincott, Williams & Wilkins; 2007; Fig. 37-2) www.freelivedoctor.com
  24. 24. Rotavirus pathogenesis <ul><li>Transmission by fecal oral route; fomites </li></ul><ul><ul><li>10 12 particles/ml in stool; infection can result from 10 particles </li></ul></ul><ul><li>Major cause of epidemic diarrhea in infants and young children </li></ul><ul><li>Highly infectious, 90% of children are seropositive by age 3 </li></ul><ul><li>Incubation period less than 48 hr </li></ul><ul><li>Fever, vomiting, watery diarrhea dehydration </li></ul><ul><ul><li>No blood or leukocytes in stool </li></ul></ul><ul><ul><li>Virus replicates in epitheal cells of villi in small intestine </li></ul></ul><ul><ul><li>Damage to epithelium major cause of diarrhea </li></ul></ul><ul><ul><li>One virus gene product is an enterotoxin </li></ul></ul><ul><ul><li>Causes loss of electrolytes and prevents readsorption of water </li></ul></ul><ul><li>Self limiting; can be fatal in malnourished or dehydrated children </li></ul><ul><li>Long term immunity </li></ul>www.freelivedoctor.com
  25. 25. Rotavirus vaccines <ul><li>First live vaccine (bovine and monkey viruses, 1999) </li></ul><ul><ul><li>Withdrawn from market because of intussusception </li></ul></ul><ul><li>New live, oral vaccine RotaTeq licensed Feb. 2006. </li></ul><ul><ul><li>Contains five live reassortant viruses of human and bovine origin </li></ul></ul>www.freelivedoctor.com
  26. 26. Rotavirus <ul><li>Structure </li></ul><ul><ul><li>Naked double shell capsid </li></ul></ul><ul><ul><li>11 segment double stranded RNA genome </li></ul></ul><ul><li>Pathogenesis </li></ul><ul><ul><li>Fecal oral transmission </li></ul></ul><ul><ul><li>Replication in cytoplasm </li></ul></ul><ul><ul><li>Fever, vomiting, diarrhea in infants and young children </li></ul></ul><ul><ul><li>Incubation period less than 48 hr, highly infectious </li></ul></ul><ul><ul><li>Infection of intestinal epithelium causes loss of electrolytes and prevents readsorption of water </li></ul></ul><ul><ul><li>Long term immunity; asymptomatic infection in adults </li></ul></ul><ul><li>Diagnosis </li></ul><ul><ul><li>viral antigen detection </li></ul></ul><ul><li>Treatment/prevention </li></ul><ul><ul><li>RotaTeq live, oral vaccine </li></ul></ul>www.freelivedoctor.com

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