Micro Test 4: Negative Strand RNA Viruses

  1. Viruses are classified by
    • Genome type
    • Morphology
  2. Name the single stranded (- sense) RNA viruses
    • Non-Segmented:  Measles, Mumps RSV
    • Segmented:  Influenza
  3. + or - RNA strand:  Which one is infectious on its own?
    + strand is infectious on its own

    - (non-segmented strands) must carry equipment (RdRp) to make them into + strands
  4. Enzyme that performs transcription of - sense RNA
    VIRAL RNA-dependent RNA polymerase (RdRp)
  5. In addition to performing transcription, the viral RdRp
    • synthesizes the 5' methylguanosine cap
    • synthesizes polyA tail (many fall off, some reinitiate)

    *RdRp stutters at gene boundaries
  6. 5 genes of VSV RNA synthesis
    Two most highly synthesized by RdRp

    GL are always at lower doses than NP
  7. Family Rhabdoviridae
    Genus?- Virus?
    Genus- Virus?
    • Vesculovirinae- Vesicular Stomatitis Virus (VSV)
    • Lyssavirinae- Rabies Virus
  8. Animal pathogen
    "Work horse" of RNA virus biology
    Vesciular Stomatitis Virus (VSV)
  9. Family Paramyxoviridae
    • Paramyxovirinae
    •           Respirovirus (HuPIV-1, -3)
    •           Morbillivirus (Measles, rinderpest)
    •           Rubulavirus (Mumps- HuPIV-2, -4)
    • Pneumovirinae
    •           Pneumovirus (Respiratory Syncytial Virus- RSV)
    •           Metapneumovirus:  Human metapneumovirus (HMPV)
  10. Large negative strand viruses associated w/ hemorrhagic fevers
    Filoviridae family

    *Highly transmissible among humans (highly virulent, typically initiated by epizoonotic transfer, then seen as outbreak in human population)
  11. Filoviridae are what level pathogen
    BSL-4 pathogen (Ebolavirus, Marburg Virus)
  12. Structural Protein:  Coats RNA, nucleoprotein
    N protein (nucleoprotein)
  13. Replication Protein:  Makes RNA dependent Pol in conjunction with large replicase (L)
    P protein (Phosphoprotein)
  14. Structural Protein:  Matrix protein (gives structural integrity of virus)
    M protein (matrix)
  15. Receptor Binding Proteins:  Encode for glycoproteins (need binding function to bind to host cell and fusion function)
    G/F/HN (Glycoprotein, Fusion, Haemagglutinin, Neuraminidase)

    *F can also code for fusion protein
  16. Does RSV agglutinate RBC?
  17. Paramyxovirus Attachment:  Occurs via
    Viral glycoprotein
  18. Paramyxovirus Attachment:  Some viruses bind to _____
    Sialic acids

    *Some also agglutinate RBCs (RSV does NOT agglutinate RBCs)
  19. Paramyxovirus Attachment:  Viruses that agglutinate RBCs
    • HN (Parainfluenza, measles) or H (mumps)
    • HN proteins also have neuraminidase activity in vitro- "Receptor Destroying Enzyme"
  20. Neuraminidase activity of HN proteins in vitro is mediated by
     Receptor Destroying Enzyme (RDE)
  21. Paramyxoviruses that don't hemagglutinate (use receptors other than sialic acid)
    • VSV
    • RSV (G proteins)
  22. Reason a vaccine can't be developed for VSV and RSV
    Both are heavily glycosylated
  23. RSV G proteins also have function in
  24. Major target of neutralizing Abs in Paramyxoviruses
    Attachment (glycoproteins)
  25. RDE binds
    Sialic acid on surface and chops them off
  26. Common constituents of N and O-linked sugars
    Sialic Acids
  27. Sialic Acid Present or Absent:  Agglutinate RBCs
  28. Sialic Acid Present or Absent:  Don't hemagglutinate RBCs
  29. F protein
    • HPIV-1
    • Participates in fusion
    • Undergoes huge conformational change
  30. Act in concert to promote fusion of Paramyxoviruses
    H(N), F proteins

    HN-F interactions required to activate F in some viruse, prevent F activation in others
  31. Fusion of Paramyxoviruses:  pH-dependent or pH-independent
    pH independent (may or may not occur at the cell surface)
  32. RSV is a major problem in what populations?
    Peds and geriatrics
  33. Most important VIRAL respiratory tract pathogen in infants and young children
    RSV (Respiratory Syncytial Virus)
  34. Man is only known host
  35. Serotypes and genotypes of RSV
    • Two serotypes (A, B)
    • Multiple genotypes
  36. RSV infects what portion of respiratory tract
    Both upper and lower respiratory tract
  37. Major cause of bronchiolitis and pneumonia (primary viral pneumonia, not bacterial)

    • 25-40% of all RSV cases
    • 40-50% of infants hospitalized with bronchiolitis are RSV+
    • 25% of those w/ pneumonia are RSV+
  38. RSV Immunity
    Immunity is transient (requires repeated exposure)
  39. By age 2, 90% of children have been infected at least once with ____ (In most children it's just a sniffly little cold.)
  40. RSV Clinical Disease:  Transmission
    • Droplets (entry via eyes, nose, mouth)
    • Fomites (self-inoculation via touch)
    • Nosocomial transmission is common
  41. RSV is most common during what seasons
    Winter-spring (Except for Fl, RSV co-circulates w/ influenza virus from mid-October to mid-March)
  42. RSV Clinical Disease:  Incubation Period
    4-6 days
  43. Do most RSV cases require hospitalization?
    No, most cases do NOT require hospitalization.  Most children recover uneventfully in 1-2 wks
  44. RSV Clinical Disease:  Symptoms
    • Initial:  Runny nose, loss of appetite
    • 1-3 days later:  Cough, sneezing fever, wheezing
  45. RSV in adults (usually elderly) causes
    Mild URTI
  46. Severe RSV is most common in what population
    • Children 2-6 months
    •         Premature infants (<6 wks of age)
    •         Infants < 24 montsh with chronic lung conditions (e.g. Cystic Fibrosis)
    •         Infants in day care, those w/ older sibs, not breastfed, exposed to cigarette smoke, or of lower SES.
    • (Also seen in elderly, immunocompromised)
  47. RSV begins as?
    Progresses to?
    • Begins as febrile URTI
    • Progresses to bronchiolitis
    • Recovery is prolonged

    Severe RSV can lead to prolonged hypoxia which can cause brain damage (resulting in a lifelong disability)- severe RSV is occassionaly fatal
  48. RSV Tx
    • Supportive care-
    •        Supplemental O2
    •        Suctioning of mucus
    •        Intubation
  49. Successfully used IV in RSV post lung transplant, but not usually used in US due to side effects
  50. RSV Diagnosis:  Test
    Rapid Antigen Tests- CLIA waived, Takes 15 min)

    • Lab:
    • ELISA
    • RT-PCR
    • Culture
  51. RSV Prevention
    • Barrier Methods:  Access restriction, avoidance, handwashing PPE (glove-gown-mask)
    • Passive Immunization- RepsiGam, Palivizumab
    •     Consider this for infants at risk for serious disease
  52. Purified RSV-Ig delivered IV

    *There is not clinical benefit in treating an RSV+ patient with RSV-IVIg
  53. Humanize monoclonal Ab targeted to F protein of RSV
     Palivizumab (Synagis)
  54. Passive Immunization of RSV: Drawbacks
    • Expensive
    • Injection must be given monthly
  55. Withold MMR and VZV vaccines for 9 months in patients who received
    RSV-IgIV (but not for those receiving Synagis)
  56. HMPV
    Human Metapneumovirus

    Genus: Metapneumovirus
  57. HMPV causes
    Mild-severe RTIs (cough, bronchiolitis, pneumonia, accompanied by high fever, myalgia, and vomiting)

    Symptoms/seasonality identical to RSV
  58. Difficult to distinguish from influenza in the elderly
  59. Estimated that all children are HMPV seropositive by age
  60. HMPV is responsible for what percentage of URTIs
  61. Parainfluenza Viruses?
    Genus- Respirovirus

    • HuPIV-1
    • HuPIV-3
    • HuPIV-2
    • Hu-PIV-4
  62. Principal agent of croup in 0.5- 3 year old children
  63. Second-leading cause of bronchiolitis and pneumonia in 1-3 year olds
  64. Also linked to serious URTI in children
  65. Parainfluenza virus that has less severe URTI
  66. Human Bocavirus (parovirus) seen in
    children <5 hospitalized for URTI (also found in healthy children)
  67. Measles, Mumps, and Rubella
    • Once a normal part of childhood, but now controlled with MMR vaccine.
    • Currently reemerging due to reduced vaccination rates
  68. Measles Virus: Genus
  69. Measles Clinical Highlights: Rash?  Infectious?
    • Rash= days 7-14
    • Infectious= days 6-10
  70. Measles Clinical Highlights: Prodrome
    • Days 6-8
    • Respiratory symptoms- high fever, cough, rhinitis (coryza), malaise (feeling cruddy), photophobia
    • Patient is highly infectious
  71. Measles Clinical Highlights:  Days 8-10
    • Koplik's Spots
    • Seen in 90% of cases
  72. Elevated pinpoint white spots on red areolae (said to have bluish center)
    Present on buccal surface opposite molar teeth
    Koplik's Spots
  73. Measles Clinical Significance:  Measles Rash
    • Days 10-16
    • Maculopapular (raised w/ flat top) rash
  74. Red measles appear first on
    • forehead (thought to be immune-mediated)
    • Moves in wave to extremities
    • Patient no longer highly infectious by this point
  75. Spread by aerosol droplets, man is the only host
    Measles virus

    *Related in part to poor nutrition
  76. Measles uses CD95 receptor (a component of the immune system) and is therefore
  77. Measles sequellae include
    • Encephalitis
    • Viral pneumonia
    • Bacteria infections
    • Subactue Sclerosing Panencephalitis (SSPE)
  78. Measles tx
  79. MMR vaccine
    Live attenuated virus

    • 2 doses:
    • 1st @ 12-15 months
    • 2nd @ 4-6 years

    *If given only once, 5% remain susceptible to infxn
  80. Why can't MMR vaccine be given at less than 9 months
    Maternal Ab may block virus replication and prevent development of immunity
  81. Single serotype of this virus circulates worldwide
  82. Why get vaccine in US?
    • Vaccination needed in US be/c virus continues to circulate outside NA and Europe. 
    • Cases typically associated w/ international travel of unvaccinated persons.
    • Infected person in US can spread disease among unvaccinated ppl in US.
  83. Eradication Aim
    Achieve a level of immunity in entire population greater than herd immunity threshold.
  84. Measles herd immunity threshold
    • 93-95%
    • (Higher than smallpox herd immunity threshold= 80-85%)
  85. Mumps virus: Genus
  86. Phases of mumps virus that can lead to spread
    Both primary and secondary viremic phases

    But recovery typically provides lifelong immunity
  87. Mumps Complications
    • Meningitis
    • Orchitis (inflammation of testes)
    • Oophritis (inflammation of ovaries)
  88. Grown in chicken embryo fibroblsats
    Measles, mumps

    Rubella is propagated in embryonic lung fibroblasts
  89. Can tramit among individual in close contact (colleges, camps) when > 10 years has passed since last immunization
  90. Rubella Virus:
    • Family:  Togaviridae
    • Genus:  Rubivirus
  91. Rubella Virus:  Genome
    + sense ssRNA
  92. German or 3-day measles
    mild childhood illness accompanied by rash caused by rubella virus
  93. Rubella congenital infxn
    Infxn in 1st trimester of pregnancy leads to in utero infxn of fetus
  94. Congenital Rubella Syndrome (CRS)
    • Deafness 67%
    • Heart disease 48%
    • Developmental delay 45%
    • Retinopathy 39%
    • Cataracts 29%
    • Purpura 23%
  95. Rubella vs. Measles
    • Rubella is:
    • Milder illness, short duration
    • No Kplik's spots
    • More subclinical cases
    • Rarer
  96. Paramyxovirus:  Causes neurological disease in horses, cattle and sheep.
    Anti-Borna Abs have been detected in humans w/ psychiatric disease (controversial)
    Bornavirus (Bornaviridae)
  97. Fatal epizootic disease in horses and humans (SE Asia, NE Australia)
    Fruit bat may be natural host
    Hendra Virus (formerly equine morbillivirus)
  98. Fatal infections in pigs and pig workers in SE Asia
    Bats implicated in transmission
    Nipah virus
Card Set
Micro Test 4: Negative Strand RNA Viruses
Micro Test 4: Negative Strand RNA Viruses (Orthoviruses, Paramyxoviruses)