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This was not officially given to us...please use your judgement...thank you!

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  1. 1. Picornaviruses Eva L. Dizon M.D.,F.P.P.S
  2. 2. Objectives <ul><li>1.To describe picornaviruses as to its characteristics, genome, structure </li></ul><ul><li>2. To know the different genus and species of family picornaviridae </li></ul><ul><li>3. To know the process of replication of picornaviruses </li></ul><ul><li>4. To know the different diseases caused by picornaviruses as to mode of transmission, pathogenesis, signs and symptoms, diagnosis , treatment and prevention </li></ul>
  3. 3. Picornavirus <ul><li>Picornaviruses are among the most diverse (more than 200 serotypes) and 'oldest' known viruses (temple record from Egypt ca. 1400 B.C.). </li></ul><ul><li>FMDV was one of the first viruses to be recognized - Loeffler and Frosch 1898. </li></ul><ul><li>Poliomyelitis as a viral disease was first recognized by Landsteiner and Popper, 1909 (though the virus was not isolated until the 1930's. Name: 'Pico (Greek = very small) RNA Viruses'. </li></ul>
  4. 4. Classification + sense RNA viruses Porcine teschovirus Teschovirus Aichivirus Kobuvirus Equine rhinitis B virus Erbovirus Human parechovirus Parechovirus Hand foot and mouth virus O Aphtovirus Encephalomyocarditis virus Cardiovirus Human Rhinovirus Rhinovirus Hepatitis A Hepatoviruses Poliovirus, Enterovirus, Coxsackie,Echovirus Enteroviruses Picornaviridae Species Genus Family
  5. 5. Genome <ul><li>The genome consists of one s/s (+)sense RNA molecule of between 7.2kb (HRV14) to 8.5kb (FMDV). </li></ul><ul><li>Genomic RNA is infectious (~1x106-fold less infectious than intact particles, although infectivity is increased if the RNA is introduced into cells by transfection) - CHARACTERISTIC OF (+)SENSE RNA VIRUSES !!! </li></ul><ul><li>There is a long (600-1200 base) untranslated region at the 5' end (important in translation, virulence and possibly encapsidation and a shorter 3' untranslated region (50-100 bases) - important in (-)strand synthesis. </li></ul>
  6. 6. Genome <ul><li>The 5' UTR contains a 'clover-leaf' secondary structure known as the IRES: Internal Ribosome Entry Site </li></ul><ul><li>The rest of the genome encodes a single 'polyprotein' of between 2100-2400 aa's. </li></ul><ul><li>Both ends of the genome are modified, the 5' end by a covalently attached small, basic protein VPg (~23 AA's), the 3' end by polyadenylation (polyadenylic acid sequences are not genetically coded, there is a 'polyadenylation signal' upstream of the 3' end as in eukaryotic mRNAs): </li></ul>
  7. 7. Structure <ul><li>The particle is 27-30nm in diameter (depending on type and degree of desiccation), while the length of the genome (stretched-out) is ~2,500nm therefore the genome is tightly packed into the capsid </li></ul>
  8. 8. Structure <ul><li>The capsid consists of a densely-packed icosahedral arrangement of 60 protomers, each consisting of 4 polypeptides, VP1, 2, 3 and 4 - all derived from cleavage of the original protomer VP0. </li></ul>
  9. 9. Genome
  10. 10. <ul><li>VP -virion polypeptide </li></ul><ul><li>VPg - important in the packaging of genome into the capsid and iniating viral RNA synthesis </li></ul><ul><li>Naked picornavirus genome is sufficient to infect cells </li></ul><ul><li>VP1 - proteins at the vertices of the virion that contain a canyon structure to which the receptor binds </li></ul><ul><li>VP4 - protein released after binding and the virion weakens </li></ul>
  11. 11. Receptors Adhesion Molecule VCAM Vascular cell adhesion molecule 1 EMCV Immunoglobulin like CD 155 3 Poliovirus Regulator of complement activator Decay accelarating factor (DAF) ,CD55 6 Echovirus Integrin like VLA -2 2 Echovirus ICAM 1 3 Coxsackie A Low density lipoprotein receptor (LDLR) 10 Human rhinovirus Immunoglobulin like ICAM 1,CD 54 91 Human rhinovirus Description Receptors # of Serotypes Virus
  12. 12. Replication <ul><li>VP1 (receptor binds)  VP4 (virion weakened)  release of genome  binds to ribosomes  polyprotein containing all viral protein sequences is synthesized within 10-15 mins of infection  polyprotein is cleaved by viral protease  viral RNA-dependent RNA polymerase generates a negative strand RNA template from which the new mRNA/genome and templates can be synthesized. </li></ul><ul><li>VP0,VP1,VP3 are cleaved and assembled into subunits  5 subunits into protomer and 12 pentamers to form procapsid  genome is inserted into procapsid  VP0 cleaved into VP2 and VP4 to complete capsid and the viron is released from the cell. </li></ul>
  13. 13. Replication
  14. 14. Translation <ul><li>The kinetics of Picornavirus replication are rapid, the cycle being completed in from 5-10 (typically 8) hours. </li></ul><ul><li>Genomic RNA is translated directly by polysomes, but ~30 min after infection, cellular protein synthesis declines sharply, almost to zero, this is called 'SHUTOFF' - the primary cause of c.p.e: </li></ul>
  15. 15. Time after infection <ul><li>~1-2h Sharp decrease in cellular macromolecular synthesis; margination of chromatin (loss of homogeneous appearance of nucleus) ~2.5-3h Start of viral protein synthesis; vaculoation of cytoplasm, beginning close to nucleus & spreading outwards ~3-4h Permeabilization of plasma membrane ~4-6h Virus assembly in cytoplasm (crystals sometimes visible) ~6-10h Cell lysis; release of virus particles  </li></ul>
  16. 16. Enteroviruses <ul><li>Species: Serotypes: Bovine enterovirus 2 Human enterovirus A (coxsackie A viruses) 10 Human enterovirus B (coxsackie B viruses, echoviruses) 36 Human enterovirus C (coxsackie A viruses) 11 Human enterovirus D 2 Poliovirus 3 Porcine enterovirus A 1 Porcine enterovirus B Unassigned: 22 </li></ul>
  17. 17. Transmission Human Fecal Matter Hand Sewage Solid waste landfills Water supply Shellfish
  18. 18. Transmission <ul><li>Respiratory,oropharynx and intestinal tract </li></ul><ul><li>Viral replication is iniated in the mucosa,lymphoid tissue of tonsils and pharynx, peyer’s patches  primary viremia  spread of virus to receptor bearing target tissue  2nd phase of replication  signs and symptoms  secondary viremia </li></ul><ul><li>* Most enterovirus are cytolytic </li></ul>
  19. 19. Polio Pathogenesis
  20. 20. Poliovirus <ul><li>Clinical forms: 1.Assymptomatic illness- 90% - infection is limited to nasopharynx and GIT 2. Abortive (minor illness)- 5% - non specific febrile - fever,vomiting,malaise,sore throat within 3-5 days of illness </li></ul>
  21. 21. Poliovirus <ul><li>Clinical forms 3.Non paralytic or Aseptic meningitis 1-2%- backpains, muscle spasm,meningeal signs 4. paralytic major – 0.1 – 2% </li></ul><ul><ul><li>-appears 3-4 days after the minor illness - fever subsides producing biphasic illness </li></ul></ul><ul><li>- virus  viremia  AHC  spine, bulbar, cranial, respiratory center </li></ul>
  22. 23. Polio <ul><li>-assymetric paralysis with no sensory loss </li></ul><ul><li>-Poliovirus type 1-85% of cases </li></ul><ul><li>-Result-recovery,residual paralysis or death </li></ul><ul><li>-Bulbar form is more severe- death 75% </li></ul><ul><li>Postpolio Syndrome- occur later in life </li></ul><ul><li>30-40 years later in 20-80% of original victim </li></ul>
  23. 24. Coxsackie <ul><li>Groups- A and B </li></ul><ul><li>Clinical forms: 1.Herpangina- virus can be recovered from the lesions and feces 2. Hand foot and mouth disease- A16 3.Pleurodynia (Bornholm’s Disease)- Devil’s grip 4. Myocardial and Pleurocardial- 5. Viral (Aseptic )meningitis </li></ul><ul><li>Fever ,rash,common colds- Coxsackie and Echovirus </li></ul><ul><li>-maculopapular rash, petichial,vesicular </li></ul>
  24. 26. Enteroviruses <ul><li>-A21,A24 and Echo 11 and 20 – cause rhinoviral like syndrome </li></ul><ul><li>Acute hemorrhagic conjunctivitis- </li></ul><ul><li>-caused by Enterovirus 70 and Coxsackie A 24 </li></ul><ul><li>-I.P. 24 hours ,last for 1-2 weeks </li></ul><ul><li>Some Coxsackie B and Echovirus </li></ul><ul><li>-can be transmitted to fetus </li></ul><ul><li>-cause infection of pancreas  IDDM </li></ul>
  25. 27. Laboratory diagnosis <ul><li>1.CSF - (Polio or Enterovirus) </li></ul><ul><li>Predominance of lymphocytic pleocytosis </li></ul><ul><li>Presence of 25-500 cells/mm </li></ul><ul><li>2.Culture- </li></ul><ul><li>Polio-Pharynx- in the first few days </li></ul><ul><li>Feces- 30 days </li></ul><ul><li>CSF- rare </li></ul><ul><li>Media- Monkey/kidney Tissue </li></ul><ul><li>Coxsackie and Echovirus – Stool and throat during infection,CSF </li></ul><ul><li>Coxsackie B- media- Monkey or tumor embryo kidney cell </li></ul><ul><li>Coxsackie A-media- grow in suckling mice than tissue cell </li></ul>
  26. 28. 'New' Enteroviruses: <ul><li>Since 1969, 'new' Enteroviruses have been assigned numbers, not names: </li></ul><ul><li>Type: llness: 68 Pneumonia 69 None (?) 70 Acute haemorrhagic conjunctivitis (1969-1974 pandemic) 71 Meningitis, rhombencephalitis 72 Hepatitis A virus MMWR: Enterovirus Surveillance - United States, 1970--2005 </li></ul>
  27. 29. Treatment and prevention <ul><li>Treatment: </li></ul><ul><li>Pleconaril-inhibits penetration of picornavirus into the cell </li></ul><ul><li>Prevention: </li></ul><ul><li>IPV- Salk </li></ul><ul><li>OPV-Sabin </li></ul>
  28. 30. Rhinovirus <ul><li>Most important cause of common colds and URI </li></ul><ul><li>Self limited </li></ul><ul><li>ICAM -1 receptor </li></ul><ul><li>Labile to acid </li></ul><ul><li>Grow best in 33 C </li></ul><ul><li>Transmission- infected hands, fomites, inhalation </li></ul><ul><li>Can be infected by 1 infectious particle </li></ul><ul><li>The release of cytokine during inflammation can promote spread of virus by enchancing expression of ICAM-1 receptor. </li></ul><ul><li>Immunity is transient- 18 months </li></ul>
  29. 31. Rhinovirus <ul><li>Laboratory Diagnosis: </li></ul><ul><li>1.Nasal washing </li></ul><ul><li>2. Grow in Human diploid fibroblast </li></ul><ul><li>3. ID by acid lability </li></ul><ul><li>Treatment: </li></ul><ul><li>Enviroxime- inhibit viral RNA- dependent RNA polymerase </li></ul><ul><li>Plecoranil,Arildone,Rhodanine,Disoxaril- Blocks uncoating </li></ul><ul><li>Prevention: </li></ul><ul><li>Handwashing and Disinfection of contaminated material </li></ul>
  30. 32. Thank you