Microbiology: Viruses

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Microbiology: Viruses
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  1. Viral Structure General
    • -naked with icosahedral capsid
    • -enveloped with icosahedral capsid
    • -enveloped with helical capsid

    Enveloped viruses can have surface proteins
  2. Viral Genetics
    1. Recombination: crossing over of chromosomes

    2. Reassortment: exchange of segments, worldwide flu pandemics

    3. Complementation: 1 of 2 viruses infecting a cell has a mutation that results in non-functional protein but non-mutated virus makes a functional protein for both

    4. Phenotypic Mixing: in cells simultaneously infected with two viruses, can have mixed coating of viruses determining tropism
  3. Live Attenuated Vaccines
    "Live! One night only! See small yellow chickens get vaccinated with Sabin's and MMR! It's incredible!"

    • -Smallpox
    • -Yellow Fever
    • -Chickenpox (VZV)
    • -Sabin's Polio
    • -MMR
    • -Influenza (intranasal)

    • -no booster needed for live attenuated
    • -dangerous to give to immunocompromised or close relatives
  4. Killed Vaccines
    "RIP Always"

    • Rabies
    • Influenza (injected)
    • Polio (Salk = Killed)
    • HAV
  5. Recombinant Vaccines
    • HBV (recombinant HBsAg)
    • HPV (types 6, 11, 16, 18)
  6. DNA Viral Genomes
    -all DNA viruses are double stranded except: PARVOVIRUS = "part-of-a-virus"

    -all DNA viruses are linear except: papilloma, polyoma and hepadnaviruses
  7. RNA Viral Genomes
    -all RNA viruses are ssRNA except: REOVIRUS "like a river"
  8. Positive Stranded RNA Viruses
    "I went to a retro toga party, where I drank flavored Corona and ate hippy California pickles"

    • Retrovirus
    • Togavirus
    • Flavivirus
    • Coronavirus
    • Hepevirus
    • Calicivirus
    • Picornavirus
  9. Negative Stranded RNA Viruses
    "Always Bring Polymerase Or Fail Replication"

    • Arenavirus
    • Bunyavirus
    • Paramyxovirus
    • Orthomyxovirus
    • Filovirus
    • Rhabdovirus

    virion brings own RNA-dependent RNA pol
  10. Naked viral genome infectivity
    • INFECTIOUS:
    • -purified nucleic acid from dsDNA viruses (except poxvirus and HBV)
    • -purified nucleic acid from + ssRNA viruses

    • NOT INFECTIOUS:
    • -purified nucleic acids of - ssRNA and dsRNA viruses (require polymerases)
  11. Virus Ploidy
    -all viruses are haploid except retrovirus (diploid)
  12. DNA Virus Replication
    • -all in nucleus
    • -EXCEPT poxvirus
  13. RNA Virus Replication
    • -all replicate in cytoplasm
    • -EXCEPT influenza and retroviruses
  14. Naked Viruses
    "Give PAPP smears and CPR to a naked Heppy"

    • PAPP=DNA
    • CPR + Hepe = RNA

    • Papillomavirus
    • Adenovirus
    • Picornavirus
    • Polyomavirus

    • Calcivirus
    • Parvovirus
    • Reovirus
    • Hepevirus
  15. Where do they get those envelopes?
    • -generally from plasma membrane
    • -EXCEPT: herpesviruses (nuclear membrane)
  16. DNA Viruses
    "are HHAPPPPy viruses!"

    • Hepadna
    • Herpes
    • Adeno
    • Parvo
    • Pox
    • Papilloma
    • Polyoma
  17. Herpesviruses
    • Structure:
    • -enveloped
    • -dsDNA, linear

    • HSV1
    • HSV2
    • VZV
    • EBV
    • CMV
    • HHV6
    • HHV7
    • HHV8
  18. HSV1
    • Diseases:
    • -Gingivostomatitis
    • -keratoconjunctivitis
    • -temporal lobe encephalitis
    • -labial herpes

    • Latent in:
    • -Trigeminal ganglia

    • Transmission:
    • -respiratory secretions
    • -saliva
  19. HSV2
    • Diseases:
    • -genital herpes
    • -neonatal herpes

    • Latent in:
    • -sacral ganglia

    • Transmission:
    • -sexual contact
    • -perinatal
  20. VZV (HHV3)
    • Diseases:
    • -Varicella Zoster (chicken pox, shingles)
    • -encephalitis
    • -pneumonia

    • Latent in:
    • -Dorsal Root Ganglia
    • -Trigeminal ganglion

    • Transmission:
    • -respiratory secretions
  21. EBV (HHV4)
    • Diseases:
    • -mononucleosis
    • -Burkitt's/Hodgkin's lymphoma
    • -nasopharyngeal carcinoma

    • Presentation:
    • -fever
    • -HSM
    • -pharyngitis
    • -lymphadenopathy (post cervical)

    • Epidemiology:
    • -15-20 years

    • Diagnosis:
    • -atypical lymphocytes on blood smear (CTLs) "hugging RBCs"
    • -positive Monospot (Abs detected by agglutination of sheep or horse RBCs)

    • Latent in:
    • -B cells

    • Transmission:
    • -respiratory secretions
    • -saliva
  22. CMV (HHV5)
    ***infection in immunosuppressed patients

    • Diseases:
    • -congenital infection --> defects
    • -mononucleosis (negative monospot)
    • -pneumonia
    • -AIDs retinitis

    • Latent in:
    • -mononuclear cells

    • Transmission:
    • -Congenital
    • -transfusions
    • -sexual contact
    • -urine
    • -transplant

    • "owl's eye inclusions"
    • "sightomegalovirus"
  23. HHV6
    • Diseases:
    • -Roseola (high fevers that may cause seizures, diffuse macular rash)

    • Transmission:
    • -not determined
  24. HHV8 (KSHV)
    • Diseases:
    • -Kaposi's Sarcoma in HIV patients

    • Transmission:
    • -sexual contact
  25. HSV Identification
    -PCR

    • -Tzanck test: smear of vesicle to detect multinucleated giant cells (HSV1, HSV2, VZV)
    • "Tzanck heavens I don't have herpes!"

    -Intranuclear Cowdry A inclusions
  26. Hepadnavirus
    • Structure:
    • -Enveloped
    • -ds DNA
    • -partially circular

    • HBV
    • -acute or chronic hepatitis
    • -vaccine available
    • -not a retrovirus but has reverse transcriptase (treatment)
  27. Adenovirus
    • Structure:
    • -enveloped
    • -ds DNA
    • -linear

    • Diseases:
    • -Febrile pharyngitis: sore throat, acute hemorrhagic cystitis
    • -Pneumonia
    • -Conjunctivitis
  28. Parvovirus
    • Structure:
    • -enveloped
    • -ss DNA
    • -linear
    • ***smallest DNA virus

    • B19 Virus
    • -aplastic crisis in Sickle Cell, "slapped cheek" rash in kids
    • -erythema infectiosum (fifth disease)
    • -RBC destruction in fetus leads to hydrops fetalis and death
    • -pure RBC aplasia and RA-like sx in adults
  29. Papillomavirus
    • Structure:
    • -enveloped
    • -ds DNA
    • -circular

    • HPV
    • -genital warts (1, 2, 6, 11)
    • -CIN, cervical cancer (16, 18)

    Vaccine available
  30. Polyomavirus
    • Structure:
    • -enveloped
    • -dsDNA
    • -circular

    • JC Virus
    • -progressive multifocal leukoencephalopathy (PML) in HIV patients

    • BK Virus
    • -transplant patients
    • -commonly targets kidneys

    "JC: Junky cerebrum, BK: Bad Kidneys"
  31. Poxvirus
    • Structure:
    • -Enveloped
    • -ds DNA
    • -linear
    • ***largest DNA virus

    • Smallpox
    • -eradicated, may be used in germ warfare

    • Vaccinia
    • -cowpox ("milkmaids' blisters")

    • Molluscum contagiosum
    • -flesh colored dome lesions with central dimple
  32. RNA Viruses
    • Reovirus
    • Picornavirus
    • Hepevirus
    • Calicivirus
    • Flavivirus
    • Togavirus
    • Retrovirus
    • Coronavirus
    • Orthomyxovirus
    • Paramyxovirus
    • Rhabdovirus
    • Filovirus
    • Arenavirus
    • Bunyavirus
    • Delta virus
  33. Reovirus
    • Structure:
    • -non-enveloped, icosahedral
    • -ds RNA
    • -linear
    • -segmented (10-12)

    • Coltivirus:
    • -Colorado tick fever

    • Rotavirus:
    • -#1 cause of fatal diarrhea in children
  34. Rotavirus
    • -most important global cause of infantile gastroenteritis
    • -major cause of acute diarrhea in the US during winter
    • -esp day care centers, kindergartens

    • Pathophysiology:
    • -villous destruction with atrophy
    • -causes decreased absorption of Na and loss of K
  35. Picornavirus
    • Structure:
    • -non-enveloped, icosahedral
    • -(+) ssRNA
    • -linear

    • "PERCH"
    • Poliovirus: vaccine
    • Echovirus: aspectic meningitis
    • Rhinovirus: common cold
    • Coxsackievirus: aseptic meningitis, herpangina, hand foot and mouth disease, myocarditis
    • HAV: acute viral hepatitis

    • -RNA is translated into 1 large polypeptide
    • -cleaved by proteases

    Cause: aseptic meningitis (except rhino and HAV)

    All are enteroviruses --> F/O transmission (except rhino)
  36. Rhinovirus
    • -common cold
    • ->100 serologic types
    • -acid labile (destroyed by stomach acid) --> doesn't infect the GI tract like the other picornaviruses
  37. Hepesvirus
    • Structure:
    • -non-enveloped, icosahedral
    • -(+) ssRNA
    • -linear

    HEV
  38. Calicivirus
    • Structure:
    • -non-enveloped, icosahedral
    • -(+) ssRNA
    • -linear

    Norovirus: gastroenteritis
  39. Flavivirus
    • Structure:
    • -enveloped, icosahedral
    • -(+) ssRNA
    • -linear

    • HCV
    • Yellow Fever
    • Dengue
    • St. Louis encephalitis
    • West Nile Virus

    Arboviruses: Yellow fever, dengue, st louis encephalitis, west nile virus
  40. Yellow Fever Virus
    -arbovirus: transmitted by mosquites (Aedes)

    Reservoir: humans or monkeys

    • Symptoms:
    • -high fever
    • -black vomitus
    • -jaundice

    "flavi = yellow --> jaundice"
  41. Togavirus
    • Structure:
    • -enveloped, iscosahedral
    • -(+) ssRNA
    • -linear

    • Rubella
    • Eastern equine encephalitis
    • Western equine encephalitis
  42. Rubella
    • -"German measles"
    • -3 days

    • Symptoms:
    • -fever
    • -postauricular adenopathy
    • -lymphadenopathy
    • -arthralgias
    • -fine truncal rash that starts and head and moves down
    • -causes mild disease in children
    • -serious congenital disease

    -ToRCHeS infection
  43. Retrovirus
    • Structure:
    • -enveloped, icosahedral/complex and conical
    • -(+) ssRNA
    • -linear

    ***have reverse transcriptase

    • HTLV: T cell leukemia
    • HIV: AIDS
  44. Coronavirus
    • Structure:
    • -Enveloped, helical
    • -(+) ssRNA
    • -linear

    • -"common cold"
    • -SARS
  45. Orthomyxovirus
    • Structure:
    • -enveloped, helical
    • -(+) ssRNA, linear
    • -segmental (8)

    Influenza virus
  46. Influenza Virus
    • -hemagglutinin: viral entry
    • -neuraminidase: progeny viral release

    Patients at risk for fatal bacterial superinfection (post flu pneumonia)

    Rapid genetic changes

    Antigenic shift and drift
  47. Antigenic Shift
    • -causes pandemics
    • -reassortment of viral genome

    EG: human flu A recombines with swine flu A

    "Sudden shift is more deadly than gradual drift"
  48. Antigenic Drift
    -causes epidemics

    -minor changes based on random mutation
  49. Paramyxovirus
    • Structure:
    • -enveloped, helical
    • -(+) ssRNA
    • -linear

    • Parainfluenza: Croup
    • RSV: bronchiolitis in babies (Rx = ribavirin)
    • Measles, Mumps

    Paramyxovirus

    -surface F protein: causes respiratory epithelial cells to fuse and form multinucleated cells

    Palivizumab (monoclonal Ab against F protein): prevents pneumonia caused by RSV in preemies
  50. Measles Virus
    • Symptoms:
    • -Koplik spots: red spot with blue-white center on buccal mucosa
    • -descending maculopapular rash (presents last)

    • Possible sequelae:
    • -SSPE (subacute sclerosing panencephalitis, years later)
    • -encephalitis
    • -pneumonia (in immunosuppressed)

    ***rash includes hands and feet (vs rubella)

    • 3 Cs of measles:
    • -Cough
    • -Coryza
    • -Conjunctivitis
  51. Mumps Virus
    • Symptoms:
    • -Parotitis
    • -Orchitis
    • -aspetic Meningitis

    "Mumps makes your parotid glands and testes as big as POM-poms"

    ***can cause sterility
  52. Rhabdovirus
    • Structure:
    • -enveloped, helical
    • -(-) ssRNA
    • -linear

    Rabies
  53. Rabies
    • -bullet shaped
    • -Negri bodies: cytoplasmic inclusions

    • Pathphysiology:
    • -infects neurons (Purkinje cells in cerebellum)
    • -travels to CNS by retrograde travel up nerve axons

    -long incubation period (weeks to months)

    • Symptoms:
    • -fever
    • -malaise
    • -agitation
    • -photophobia
    • -hydrophobia
    • -paralysis
    • -coma
    • -death

    • Treatment:
    • -wound cleansing
    • -vaccination +/- rabies Ig

    **in US from bat, racoon, skunk bites
  54. Filovirus
    • Structure:
    • -enveloped, helical
    • -(-) ssRNA
    • -linear

    • Ebola
    • Marburg hemorrhagic fever

    OFTEN FATAL!!!
  55. Arenavirus
    • Structure:
    • -enveloped, helical
    • -(-) ssRNA
    • -circular
    • -2 segments

    • LCMV
    • Lassa fever encephalitis (spread by mice)
  56. Bunyavirus
    • Structure:
    • -enveloped, helical
    • -(-) ssRNA
    • -circular
    • -3 segments

    • California encephalitis
    • Sandfly/Rift Valley fevers
    • Crimean-Congo hemorrhagic fever
    • Hantavirus (hemorrhagic fever, pneumonia)
  57. Delta Virus
    • Structure:
    • -enveloped, uncertain
    • -(-) ssRNA
    • -circular

    HDV: "defective virus" that requires HBV co-infection

    "Can't have Doggie without the Boyfriend"
  58. Hepatitis mneumonics
    "The vowels hit your bowels": HAV and HEV are F/O
  59. Signs and Symptoms of ALL hepatitis viruses
    • Episodes of:
    • -fever
    • -jaundice
    • -elevated AST, ALT

    ALT > AST (vs alcoholic hepatitis, AST>ALT)
  60. HAV
    Virus: RNA picorna

    Transmission: F/O

    Carrier: No

    Incubation: short (weeks)

    HCC Risk: No

    Asymptomatic, Acute, Alone (no carriers)
  61. HBV
    Virus: DNA hepadna

    Transmission: parenteral, sexual, maternal-fetal

    Carrier: Yes

    Incubation: Long (months)

    HCC Risk: Yes (integrates into genome, acts as oncogene)
  62. HCV
    Virus: DNA flavivirus

    Transmission: blood (IVDU), post transfusion

    Carrier: Yes

    Incubation: Long

    HCC Risk: Yes from chronic inflammation

    Chronic, Cirrhosis, Carcinoma, Carrier
  63. HDV
    Virus: RNA delta virus

    Transmission: Parenteral, sexual, maternal-fetal

    Carrier: yes

    Incubation: Superinfection (short), co-infection (long)

    HCC Risk: yes

    • Defective virus, Dependent on HBV
    • superinfection --> worse prognosis
  64. HEV
    Virus: RNA hepevirus

    Transmission: F/O

    Carrier: No

    Incubation: Short

    HCC Risk: No

    **High mortality in pregnant women

    Enteric, Expectant mothers, Epidemic
  65. Anti-HAV (IgM)
    -best test to detect active hepatitis A
  66. Anti-HAV (IgG)
    -indicates prior HAV infection and/or prior vaccination

    -protects against reinfection
  67. HBsAg
    • -found on the surface of HBV
    • -indicates hepatitis B infection
  68. Anti-HBs
    -indicates immunity to hepatitis B
  69. HBcAg
    -antigen associated with core of HBV
  70. Anti-HBc
    • -IgM = acute/recent infection
    • -IgG = prior exposure or chronic infection

    -Positive during window period
  71. HBeAg
    • -different antigen in HBV core
    • -indicates active viral replication and high transmissibility
  72. Anti-HBe
    -indicates low transmissibility
  73. Locations of Hepatitis Antigens


    • SECES
    • -SE are antigens
    • -CES are antibodies
    • -in order of appearance
  74. Timecourse of Hepatitis Antigens
  75. Timecourse of Hepatitis Antigens Chart
  76. HIV Genetics
    -diploid genome (2 RNAs)

    • Genes and Proteins
    • 1. env --> gp120 and gp41
    •      -gp120: attach to CD4 cells
    •      -gp41: fusion and entry
    • 2. gag --> (p24)
    •      -capsid protein
    • 3. pol
    •      -RT
    •      -aspartate protease
    •      -integrase
  77. HIV Life Cycle
    • Virus binds CCR5 (early) or CXCR4 (late) on CD4 cells/CCR5 and CD4 on macrophages

    RT synthesizes dsDNA from RNA --> integration
  78. HIV and CCR5
    HIV binds CCR5 on CD4 cells and macrophages

    • Homozygous CCR5 mutation: immunity
    • Heterozygous CCR5 mutation: slower course
  79. HIV Diagnosis
    • 1. ELISA ("rule out" test)
    • -sensitive
    • -high false positive rate
    • -low threshold

    • 2. Western blot assay ("rule in" test)
    • -specific
    • -high false negative rate
    • -high threshold

    • 3. HIV PCR/Viral Load
    • -amount of viral RNA in plasma
    • -monitor effect of drug therapy

    • **ELISA and Western blot look for antibodies to viral proteins
    • **May be falsely negative in first 1-2 months of infection
    • **May be falsely positive in babies born to infected mothers
  80. AIDS Diagnosis
    • 1. <200 CD4 cells/mm3
    • 2. HIV+ with AIDS defining condition or CD4/CD8 ration <1.5
  81. Time Course of HIV Infection


    • Red = CD4 count
    • Blue = HIV RNA

    • "Four stages of infection:
    • 1. Flu-like (acute)
    • 2. Feeling fine (latent)
    • 3. Falling count
    • 4. Final crisis"

    **during latent phase virus replicates in lymph nodes
  82. Common diseases of HIV+ Adults
    • 1. Systemic
    •      -Histoplasma capsulatum (pulm sx)

    • 2. Dermatologic
    •      -C. albicans (thrush)
    •      -Bartonella henselae (bacillary angiomatosis)

    • 3. GI
    •      -Cryptosporidium

    • 4. Neuro
    •      -JC virus reactivation (PML)
    •      -Toxoplasma (abscesses)
    •      -Cryptococcus neoformans (meningitis)
    •      -CMV (retinitis)

    • 5. Oncologic
    •      -Kaposi's Sarcoma (HHV8)
    •      -Hairy Leukoplakia (EBV)
    •      -Non-Hodgkin's lymphoma (maybe EBV)
    •      -Squamous cell carcinoma (HPV)
    •      -CNS lymphoma (often associated with EBV)

    • 6. Respiratory
    •      -Interstitial pneumonia (CMV)
    •      -Aspergillus
    •      -pneumocystis jirovecii (pneumonia)
    •      -mycobacterium avium-intracellulare
  83. AIDS: Histoplasma capsulatum
    • Sx:
    • -low grade fevers
    • -cough
    • -HSM
    • -tongue ulcer

    • Findings:
    • -oval yeast cells within macrophages

    CD4 count <100

    **in immunocompetent hosts only causes pulmonary sx
  84. AIDS: C. albicans
    • Sx:
    • -fluffy white cottage cheese lesions
    • -thrush

    • Findings:
    • -pseudohyphae

    • CD4 count <400 --> oral
    • CD4 count <100 --> esophageal
  85. AIDS: Bartonella henselae
    • Sx:
    • -superficial vascular proliferation
    • -bacillary angiomatosis

    • Findings:
    • -bx: neutrophilic inflammation
  86. AIDS: Cryptosporidium spp
    • Sx:
    • -chronic watery diarrhea

    • Findings:
    • -acid-fast cysts in stool

    CD4 count <200
  87. AIDS: JC virus reactivation (PML)
    • Sx:
    • -encephalopathy
    • -viral reactivation --> demyelination

    CD4 <200
  88. AIDS: Toxoplasma gondii
    • Sx:
    • -brain abscesses

    • Findings:
    • -many ring-enhancing lesions on imaging

    CD4 <100
  89. AIDS: Cryptococcus neoformans
    • Sx:
    • -meningitis

    • Findings:
    • -India ink stain reveals yeast with narrow-based budding and large capsule

    CD4 count <50
  90. AIDS: CMV
    • 1. Neurologic
    • Sx:
    • -Retinitis
    • Findings:
    • -cotton wool spots on fundoscopy

    CD4 count <50

    • 2. Respiratory
    • Sx:
    • -interstitial pneumonia
    • Findings:
    • -bx: reveals cells with intranuclear "owl's eye" inclusions
  91. AIDS: Kaposi's Sarcoma
    • Sx:
    • -superficial neoplastic proliferation of vasculature

    • Findings:
    • -bx: lymphocytic infiltration

    ***DON'T confuse with bacillary angiomatosis
  92. AIDS: EBV
    -Hairy leukoplakia

    • Maybe associated with:
    • -Non-Hodgkin's lymphoma (often in oropharynx)
    • -Primary CNS lymphoma
  93. AIDS: Aspergillus fumigatus
    • Sx:
    • -invasive aspergillosis (pulm)

    • Findings:
    • -pleuritic pain
    • -hemoptysis
    • -infiltrates on imaging
  94. AIDS: Pneumocystis jirovecii
    • Sx:
    • -pneumonia

    Esp with CD4 count <200
  95. AIDS: Mycobacterium avium-intracellulare
    • Sx:
    • -TB-like disease

    Esp with CD4 count <50

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