Micro Test 4: Picorna-, Corona- and GI tract Viruses

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BrookeNH10
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198434
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Micro Test 4: Picorna-, Corona- and GI tract Viruses
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2013-02-06 19:06:25
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Micro Test Picorna Corona GI tract viruses
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Micro Test 4 Picorna, Corona, and GI tract viruses
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  1. Picornavirus:
    Family?
    6 Genus?
    • Family:  Picornaviridae
    • Genus:
    • Rhinovirus- common cold viruses (HRV)
    • Enterovirus- poliovirus, human Enterovirus A, Coxsackie A and B, ECHOvirus
    • Apthovirus- foot and mouth disease virus (cows)
    • Cardiovirus- EMCV and Mengo (mice)
    • Hepatovirus- HAV
    • Paraechovirus- diarrhea/respiratory infxns in children
  2. Picornaviridae Structure:
    Genome?
    # of ORFs?
    Enveloped?
    Nucleocapsid shape?
    # of proteins that make up virion?
    • ssRNA
    • 1 ORF
    • Naked
    • Icosahedral nucleocapsid
    • 4 proteins make up virion
  3. Receptor locatio of picrnaviridae
    Deep in cleft (on Bp1 or Bp3), Ig's can't fit into the cleft.
  4. What structure is made when picornavirus replicates?
    dsRNA structures

    *Protease cleans up the final structure
  5. Viral RNA is
    Infectious
  6. First replicative event of Picornavirus replication
    Genome is translated to yield structural and catalytic proteins
  7. Viral proteins are synthesized to form
    A large polyprotein
  8. Polyprotein is then co-translationally cleave dby
    virus-encoded proteases to generate the final products
  9. Final products of Picorna virus replication
    • 4 capsid proteins
    • 2 proteases
    • VPg
    • RDRP
  10. Directs synthesis of negative-strands via a ds replicative form
    RDRP
  11. Negative strands then serve as templates for positive strands via the multi-stranded
    Replicative intermediate
  12. 2A protease encoded by
    CxB4
  13. 2A protease cleaves (3 things)
    • viral polyprotein (via a self-processing mechanism)
    • eIF-4G -> host translational shut-off
    • Heart muscle dystrophin -> cytoskeletal dysfunction
  14. Causes infection of heart muscle myocytes
    Coxsackie B4 virus

    Significant cause of human acquired dilated cardiomyopathy

    Disease is characterized by cardiac enlargement and CHF
  15. Coxsackie B4 virus cleaves
    Dystrophin -> leads to disruption of hte extrasarcomeric cytoskeleton and loss of transmission of mechanicla force to the ECM
  16. Man is the only host for
    human enteroviruses
  17. Transmission of Enteroviruses
    Fecal-oral, droplet
  18. Clinical presentation of Enteroviruses
    Clinical presentation is NOT definitive; lab tests are needed
  19. Tx for Enteroviruses: 
    • Supportive
    • Vaccination for polio
  20. Peak incidence of Enteroviruses
    Summer/fall
  21. Enterovirus Immunity
    • Local IgA blocks infxn
    • Systemic IgG blocks paralysis due to poliovirus
  22. Infect and affect a wide range of organs and tissues
    • Enteroviruses
    • Picornaviruses
  23. Enteroviruses cause
    • Aseptic meningitis (encephalitis)
    • URTIs
    • Paralytic disease
    • Fatal generalized disease in newborns
    • Epidemic hemorrhagic conjunctivitis
  24. Exposed to poliovirus by
    ingesting it
  25. Polio virus grows in
    Oropharyngeal mucosa or gut --> then it goes to lymphoid tissue

    Once it gets into the blood, it can target more important tissues such as CNS (polio) etc.
  26. Problems with live poliovaccine
    Live vaccine can cause paralytic disease in an immunocompromised person.

    Or it can mutate and cause virus.
  27. Poliovirus percentages:
    Asymptomatic?
    Malaise?
    Paralysis?
    • Asymptomatic= 95%
    • Malaise= 1-5%
    • Paralysis= <1%
  28. Target of polio that results in paralysis (flaccid paralysis, pain; bulbar paralysis)
    Anterior horn cells
  29. Polio is a disease of
    developed countries (undeveloped countries get it when they're younger and still have maternal Ab protection)
  30. Polio Tx
    Supportive
  31. Polio Prevention
    • Salk Vaccine: IPV
    • Sabin Vaccine: OPV
  32. Salk vs. Sabin:  Dropped on sugar cubes or just dropped in your mouth
    Sabin
  33. Only 3 countries with endemic polio
    • Afghanistan
    • Pakistan
    • Nigeria
  34. Salk vs. Sabin: No virus-specific CTL response. No mucosal Ig!
    Salk
  35. Salk vs. Sabin:  Tc response and IgA, protected population; Virus specific CTL response is generated w/ mucosal Ig
    Sabin
  36. Characterized by muscle pain, and progressive muscle weakness
    Post-Polio Syndrome
  37. Enterovirus Disease:  Epidemic myalgia, intercostal pain (Devil's stitch)- unilateral thoracic chest pain

    Endemic in Danish Island
    Pleurodynia
  38. Enterovirus Disease:  A childhood infxn characterized by fever, sore throat, and vesicular lesions within throat
    Herpangina
  39. Herpangina is caused by what forms of Enteorvirus
    EnA, EnC (Coxsackievirus A)
  40. Enterovirus Disease:  A childhood infxn characterized by lesions in the mouth and on the palms and soles

    Common in pre-schoolers
    Hand-foot-mouth disease

    Coxsackievirus A6 variant is linked w/ nail loss months after initial infxn
  41. Enterovirus Disease:  Painful eye infxns that are easily spread from person-to-person
    Acute hemorrhagic conjunctivitis
  42. AHC cause by
    En70, CxA= EnC, EnD
  43. Enterovirus Disease:  A multi-system illness developing soon after birth and linked to a high fatality rate
    Neonatal disease
  44. Neonatal disease caused by
    CxB and ECHO (EnB)
  45. Enterovirus:  EnB myo- and peri-carditis in adults and children
    Cardiac Disease
  46. 3 Differential Diagnoses for mouth lesions
    • Hand-foot-mouth syndrome (enterovirus, CxA)
    • Herpangina (enterovirua, CxA)
    • Primary Herpes Gingivostomatitis (HSV-1, sometimes HSV-2)
  47. Diagnosis of aseptic meningitis is made by
    Excluding bacterial causes
  48. Meningitis:
    500-10,000 cell/ul (mostly PMNs)
    Bacterial
  49. Meningitis
    10-500 cells/ul (mostly lymphocytes)
    Viral meningitis
  50. Virus decontamination:  Bleach or alcohol?
    bleach

    alcohol only targets the capsid
  51. Rhinovirus transmission
    direct contact
  52. HRV is responsible for what percentage of:
    common colds?
    asthma exacerbations?
    • 30% of common colds
    • 50% of asthma exacerbations
  53. Rhinovirus Immunity
    Type-specific, involves mucosal IgA

    Vaccine is problematic due to large # of straings
  54. Only family of positive-strand viruses w/ a helical nucleocapsid
    Coronaviruses
  55. # of ORF proteins in coronavirus
    9
  56. 16 of Coronaviruses 28 proteins are generated by
    Polyprotein
  57. Cleavage of ORF1a/1b polyprotein is mediated by
    virus-encoded proteases -> gives rise to proteins required for RNA replication
  58. CoV ORFs 2-9 encode
    Structural proteins
  59. SARs is what type of virus
    Coronavirus
  60. Origin of SARs
    Bat-> Civet Cat -> People

    (Classic example of a zoonotic infxn in which bats play a key role)
  61. Coronavirus that causes serious URTI in elderly
    SARS

    *Can be controlled by preventative measures
  62. SARS incubation period?
    SARs duration of illness?
    • 4-5 days
    • ~11 days
  63. Increased virus shedding due to advanced disease or co-morbidities
    Super Shedder

    One of the driving forces behind the early SARS outbreak (vast majority of pts. don't transmit the virus effectively)
  64. Increased contact with respiratory secretions, contact with highly contagious pts., exposure to aerosol-generaing procedures
    Nosocomial Amplification (NA)

    One of the driving forces behind the early SARS outbreak (along with SS)
  65. SARS mortality
    10-15% overall, but increases with age
  66. SARS tx
    No specific tx
  67. SARS-CoV receptor
    Angiotensin-converting enzyme 2
  68. ACE2 is the receptor for
    SARS (CoV)
  69. SARS MoA
    Virus replication leads to hyperimmune activation which triggers pulmonary destruction
  70. Reservoir for SARS
    bats
  71. Viruses that cause GI Tract Illnesses
    • Rotavirus (Family Reoviridae)
    • Norovirus (Family Caliciviridae)
    • Astrovirus
    • Enteric adenovirus
  72. Family that rotavirus belongs to?
    Other genera within that family
    Reoviridae

    • Reovirus: minor human pathogens
    • Orbivirus
    • Coltivirus:  Colorado Tick Fever Virus
    • Rotavirus:  causative agent of severe diarrhea and vomiting (7 serogroups within genus)
  73. Structure of Rotavirus
    • dsDNA (11 segments)
    • Non-enveloped icosahedral virus
  74. Rotavirus is responsible for 5-10% of all diarrhea episodes in children <5 years old.
    Within the first 5 years of life 80% of American kids will be infected with rotavirus...immunity is lifelong
  75. Rotavirus:
    Incubation period
    Illness lasts
    • Incubation period: 1-4 days
    • Illness lasts: 5-8 days
  76. Rotavirus is most prevalent in US
    during cooler months
  77. ID50 of Rotavirus
    1-100
  78. Rotavirus transmission
    Fecal-oral route
  79. Classification of Rotaviruses is based on
    Viral capsid proteins VP4 and VP7
  80. VP4 and VP7 are viral capsid proteins for what virus?
    Rotavirus
  81. How many Rotavirus human serotypes are based on VP7
    10 (G1-G4, and G9 are the most common)
  82. P protein
    VP4
  83. G protein
    VP7
  84. Main targets of neutralizing Ab for rotavirus
    VP4 and VP7
  85. 2 Rotavirus vaccines
    RotaTeq- pentavalent, live attenuated, expresses various subtypes of human VP7 outer capsid protein (G1, G2, G3, and G4) and the human VP4 attachment protein
  86. Following the introduction of RotaTeq/RotaRix, the # of rotatvirus infxns was reduced by
    > 50%
  87. Causes 60% of foodborne illness
    Norovirus
  88. Common in day cares, cruise ships, and elderly ppl homes
    Norovirus (foodborne illness)
  89. Norovirus family
    Caliciviridae
  90. Norovirus genome
    Single molecule of + sense RNA
  91. Norovirus is divided into how man ORFs?
    3
  92. Norovirus ORF1
    Encodes a large polyprotein which undergoes proteolytic cleavage to produce viral proteins that are homologous to proteins from other ssRNA viruses

    Also encodes RNA-dependent RNA Polymerase
  93. NoV genogroup
    • 5 different genogroups
    • Based on the genome sequence of the RdRp and the capsid regions

    Only genogroups 1, 2, and 4 have been associated with human gastroenteritis
  94. Norovirus genotyping has been complicated by
    Recombinant norovirus strains
  95. Norovirus: Viral shedding
    May persist for 7-14 days
  96. Norovirus Diagnosis
    • ELISA- detection of anti-viral Abs
    • RT-PCR
    • Nucleic acid hybridization probes
  97. Rotavirus vs. Norovirus
    • Rotavirus:  Severe diarrhea, vaccine available
    • Norovirus:  Brief GItis, no vaccine

    Diarrhea is the result of both direct and indirect effects of virus
  98. Viral GIitis
    Shortening of the intestinal villi leads to malabsorption of fats and sugars resulting in profuse watery diarrhea
  99. Enteric Adenoviruses
    Ad40, Ad41 may account for 4-15% of children hospitalized with VGI.
  100. Enteric Adenoviruses:
    Incubation period
    Duration of illness
    Symptoms vs. rotavirus
    • IP= 8-10 days (longer than Rotavirus)
    • DoI= 6-12 days (longer than Rotavirus)

    Symptoms less severe than with rotavirus
  101. Similar to caliciviruses in shape and genome organization.  Major cause of childhood diarrhea worldwide.  1-4 day incubation, ~4 days of illness, less severe than rotavirus
    Astroviruses
  102. Viral Vaccines:  0-6 years
    HBV (3), Rotavirus (2-3), Poliovirus (4-5), Influenza virus (yearly), MMR (2), Varicella (2), HAV (2)
  103. Viral Vaccines: 7-18 years
    • HPV
    • Influenza virus
  104. Viral Vaccines 19->65 years
    Zoster (1), Influenza (yearly)
  105. Viral Vaccines: Others
    Rabies, Japan B Encephalitis, Yellow Fever Virus, Vaccinia (smallpox)

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