Picornaviruses
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Picornaviruses

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  • 1. Picornaviruses Eva L. Dizon M.D.,F.P.P.S
  • 2. Objectives
    • 1.To describe picornaviruses as to its characteristics, genome, structure
    • 2. To know the different genus and species of family picornaviridae
    • 3. To know the process of replication of picornaviruses
    • 4. To know the different diseases caused by picornaviruses as to mode of transmission, pathogenesis, signs and symptoms, diagnosis , treatment and prevention
  • 3. Picornavirus
    • Picornaviruses are among the most diverse (more than 200 serotypes) and 'oldest' known viruses (temple record from Egypt ca. 1400 B.C.).
    • FMDV was one of the first viruses to be recognized - Loeffler and Frosch 1898.
    • 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'.
  • 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. Genome
    • The genome consists of one s/s (+)sense RNA molecule of between 7.2kb (HRV14) to 8.5kb (FMDV).
    • 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 !!!
    • 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.
  • 6. Genome
    • The 5' UTR contains a 'clover-leaf' secondary structure known as the IRES: Internal Ribosome Entry Site
    • The rest of the genome encodes a single 'polyprotein' of between 2100-2400 aa's.
    • 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):
  • 7. Structure
    • 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
  • 8. Structure
    • 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.
  • 9. Genome
  • 10.
    • VP -virion polypeptide
    • VPg - important in the packaging of genome into the capsid and iniating viral RNA synthesis
    • Naked picornavirus genome is sufficient to infect cells
    • VP1 - proteins at the vertices of the virion that contain a canyon structure to which the receptor binds
    • VP4 - protein released after binding and the virion weakens
  • 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. Replication
    • 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.
    • 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.
  • 13. Replication
  • 14. Translation
    • The kinetics of Picornavirus replication are rapid, the cycle being completed in from 5-10 (typically 8) hours.
    • 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:
  • 15. Time after infection
    • ~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 
  • 16. Enteroviruses
    • 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
  • 17. Transmission Human Fecal Matter Hand Sewage Solid waste landfills Water supply Shellfish
  • 18. Transmission
    • Respiratory,oropharynx and intestinal tract
    • 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
    • * Most enterovirus are cytolytic
  • 19. Polio Pathogenesis
  • 20. Poliovirus
    • 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
  • 21. Poliovirus
    • Clinical forms 3.Non paralytic or Aseptic meningitis 1-2%- backpains, muscle spasm,meningeal signs 4. paralytic major – 0.1 – 2%
      • -appears 3-4 days after the minor illness - fever subsides producing biphasic illness
    • - virus  viremia  AHC  spine, bulbar, cranial, respiratory center
  • 22.  
  • 23. Polio
    • -assymetric paralysis with no sensory loss
    • -Poliovirus type 1-85% of cases
    • -Result-recovery,residual paralysis or death
    • -Bulbar form is more severe- death 75%
    • Postpolio Syndrome- occur later in life
    • 30-40 years later in 20-80% of original victim
  • 24. Coxsackie
    • Groups- A and B
    • 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
    • Fever ,rash,common colds- Coxsackie and Echovirus
    • -maculopapular rash, petichial,vesicular
  • 25.  
  • 26. Enteroviruses
    • -A21,A24 and Echo 11 and 20 – cause rhinoviral like syndrome
    • Acute hemorrhagic conjunctivitis-
    • -caused by Enterovirus 70 and Coxsackie A 24
    • -I.P. 24 hours ,last for 1-2 weeks
    • Some Coxsackie B and Echovirus
    • -can be transmitted to fetus
    • -cause infection of pancreas  IDDM
  • 27. Laboratory diagnosis
    • 1.CSF - (Polio or Enterovirus)
    • Predominance of lymphocytic pleocytosis
    • Presence of 25-500 cells/mm
    • 2.Culture-
    • Polio-Pharynx- in the first few days
    • Feces- 30 days
    • CSF- rare
    • Media- Monkey/kidney Tissue
    • Coxsackie and Echovirus – Stool and throat during infection,CSF
    • Coxsackie B- media- Monkey or tumor embryo kidney cell
    • Coxsackie A-media- grow in suckling mice than tissue cell
  • 28. 'New' Enteroviruses:
    • Since 1969, 'new' Enteroviruses have been assigned numbers, not names:
    • 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
  • 29. Treatment and prevention
    • Treatment:
    • Pleconaril-inhibits penetration of picornavirus into the cell
    • Prevention:
    • IPV- Salk
    • OPV-Sabin
  • 30. Rhinovirus
    • Most important cause of common colds and URI
    • Self limited
    • ICAM -1 receptor
    • Labile to acid
    • Grow best in 33 C
    • Transmission- infected hands, fomites, inhalation
    • Can be infected by 1 infectious particle
    • The release of cytokine during inflammation can promote spread of virus by enchancing expression of ICAM-1 receptor.
    • Immunity is transient- 18 months
  • 31. Rhinovirus
    • Laboratory Diagnosis:
    • 1.Nasal washing
    • 2. Grow in Human diploid fibroblast
    • 3. ID by acid lability
    • Treatment:
    • Enviroxime- inhibit viral RNA- dependent RNA polymerase
    • Plecoranil,Arildone,Rhodanine,Disoxaril- Blocks uncoating
    • Prevention:
    • Handwashing and Disinfection of contaminated material
  • 32. Thank you