Virology exam 3

  1. most common type of hepatitis 

    second most common?
    A

    then B
  2. Hepatitis found in pregnant women found in water and rare
    Hepatitis E - abortion
  3. Hepatitis mostly in aids patients
    Hepatitis G
  4. Hepatitis A,C,G,E genome?
    +ssRNA
  5. Hepatitis D genome

    Hepatitis B genome

    torque teno

    sentinel virus
    -ssRNA

    DNA (partial ds)

    ssDNA

    ssDNA (circular)
  6. Enveloped hepatitis
    B,C,D,G
  7. Hepatitis A symptoms - what are the other 3 symptoms?

    – Fatigue
    – Abdominal pain

    – Nausea and vomiting
    • – Dark urine
    • – Jaundice (occurs in 70–80% of individuals older than 14 years of age, less likely to occur in children)
    • – Loss of appetite
  8. Hepatitis B

    Endemic areas: Major model of spread is mother (carrier) to infant

    what are the other 3 high risk groups for hepatitis B aside from these 2

    – Individuals with multiple sexual partners
    – Institutionalized patients
    • – IV drug users
    • – Hemodialysis patients
    • – Healthcare workers
  9. Average incubation period for hepatitis A, B, C, and and E
    A- 30 days

    B- 80 days 

    C- 6-7 weeks

    E- 40 days
  10. Hepatitis B ____ % of individuals have no signs or symptoms
    30%
  11. Chronic HBV infections occur in ____ of cases
    5–10%
  12. Death from chronic liver disease results in
    ______% of individuals
    15–25%
  13. _____% of U.S. population is infected with HCV
    1.8%
  14. Hepatitis C virus

    Between _____ and ____ of infected persons
    experience a chronic infection, resulting in
    chronic liver disease
    55% and 85%
  15. – ____% of IV drug addicts test positive for HDV
    39–90%
  16. hepatitis E virus

     _____ % mortality in general population
    _____ % mortality in pregnant women
    1–3%

     15–25%
  17. Torque Teno Virus
     
    – Found in 1997 using _______
    representational difference analysis
  18. Lab Diagnosis of viral hepatitis infections based on:

    – Symptoms and physical findings

    – Elevated antibodies against a virus (serology testing,
    ELISA)

    and TWO more...
    – Blood tests for elevated liver enzymes (AST and ALT)

    – Detection of viral proteins or genomes (nucleic acid tests)—require specialized laboratories
  19. – Alanine Aminotransferase
    – Your body uses ALT to break down
    food into energy. Normally, ALT
    levels in the blood are low. If your
    liver is damaged, it will release more
    ALT into your blood and levels will
    rise. (ALT used to be called serum
    glutamic-pyruvic transaminase, or
    SGPT).
    • – Alanine Aminotransferase
    • – Your body uses ALT to break down
    • food into energy. Normally, ALT
    • levels in the blood are low. If your
    • liver is damaged, it will release more
    • ALT into your blood and levels will
    • rise. (ALT used to be called serum
    • glutamic-pyruvic transaminase, or
    • SGPT).
  20. • Hepatitis A–E virus structure

    – _____ shape and _____ symmetry
    – ____ nm in diameter
    – Enveloped (B, C, D) or nonenveloped (A or E)
    – HAV is _____ and bile resistant
    Spherical , icosahedral

    28–50 nm

    acid
  21. HAV
    • Very stable, naked ______
    picornavirus
  22. 1963: Antibodies in the serum of a New York
    hemophiliac reacted with an antigen present in the blood of an Australian aborigine infected with hepatitis
    • Australia antigen was the _______

    • Further experiments by _____ led to the
    discovery of the _____ (complete infectious HBV)
    hepatitis B surface antigen (HBsAg)

    David Dane

    Dane particle
  23. • Three types of HBV particles present during
    infection:

    1. Spherical 17–25 nm particle: Most abundant HBV particle in carriers

    2. Noninfectious filamentous particles: Up to ______ nm in length; less numerous

    3. Infectious Dane particle: 42 nm diameter; contains _____, ______, and _____ associated with viral genome
    200 nm


    viral DNA polymerase (DT)

    protein kinase C

    heat shock 90 protein
  24. HBV genome
    – HBV is a hepadnavirus
    - (blank 1)
    – Full length strand is 3.2 kb
    – Shorter stand is 1.7 kb in length
    - (blank 2)
    – Circular partially dsDNA

    – Uses a replication strategy common to retroviruses
  25. Hepatitis C virus

    • Icosahedron-shaped, enveloped, +ssRNA flavivirus
    • Little known about HCV ultrastructure
    ( blank)
    • Similar to picornaviruses (poliovirus), except HCV
    particles are enveloped
    • Viral nucleic acid cloned in 1989
    • Only flavivirus not transmitted by arthropod vectors
  26. HVC genome
    – _____ kb in length
    – Contains______ and one long ORF that encodes polyprotein precursor
    – Translated to host ribosomes by ______ translation
    9.2

    internal ribosome entry site (IRES)

    cap-independent translation
  27. Hepatitis E virus

    • ______ transmission
    • HEV structure
    – _____ genome
    – Clinically indistinguishable from HAV, but HEV particles much _____ stable
    – Viruses 32–34 nm in diameter, (enveloped or non-enveloped?), and
    icosahedral shaped


    • HEV genome
    – Approx 7.2 kb in length
    – Short 5′ and 3′ noncoding regions
    – 3′ end contains a poly(A) tail
    – (how many?) ORFs
    • Overall knowledge of HEV replication is poor
    Fecal–oral

    +ssRNA

    less

    nonenveloped

    3
  28. Many variants of HBV and HCV because _______


    how many major genotypes of HEV ?

    One ______ of HAV, but at least 7 different
    _______
    – Viral polymerases lack proofreading ability

    4

    serotype

    genotypes
  29. Hepatitis A virus

    – Management
    • _________
    • _________

    – Prevention
    • Handwashing and proper sanitary disposal of human feces
    • __________

    – Vaccines: Formalin-inactivated, cell
    culture−produced, whole virus
    No specific treatment

    Supportive care


    Passive immunity via immunoglobulin injection
  30. 6 licensed drugs: Interferon α-2b, lamivudine,
    adefovir, dipivoxil, entecavir, telbivudine, and
    tenofovir
    Drugs to manage hepatitis B virus

    • – Prevention
    • • Antibodies effective if used shortly after
    • exposure
    • • Immunoglobulin used as an adjunct to vaccine
  31. What type of vaccine is a hepatitis B vaccine?
    Recombinant DNA vaccine in yeast
  32. Hepatitis C

    – Management
    • _____% of infections progress to chronic liver disease
    • Pegylated interferon α-2a or pegylated interferon α-2b and/or _______
    • Close monitoring of ______ treatment
    necessary due to adverse reactions
    • _____% of patients cannot tolerate side effects, such as _______
    85%

    ribavirin

    interferon/ribavirin

    50%

    anemia
  33. Greek scholars coined the term herpes, which
    means to ______ in reference to the
    spreading of herpetic lesions
    “creep or crawl”
  34. Herpes simplex 1
    ______ of the eye (leading cause of
    corneal blindness in the U.S.)
    _______ (“mat herpes”
    transmitted during wrestling)
    _______ (seen in contact sports
    like rugby) hands and wrists
    Herpes keratitis

    – Herpes gladitorium

    – Herpes rubeiorum
  35. Herpes simplex 1 

    Reactivation associated with the following:
    (blank 0)
    – Sexual contact
    (blank 1)
    – Temperature changes (hot or cold)
    – Excessive UV light exposure
    (blank 2)
    – Pregnancy
    (blank 3)
    (blank 4)
    – Excessive fatigue
    • – Immune suppression by cytotoxic drugs
    • – Physical and emotional stress
    • – Menstruation
    • – Lactation
    • – Malnutrition
  36. Only herpesvirus that spreads through airborne mode
    of transmission (coughing or sneezing)
    chicken pox
  37. Other symptoms: chicken pox
    – Fever
    – Malaise
    – Average of ______ lesions on the body during an attack
    – Blisters dry and form scabs in 4–5 days

    • Adult complications:
    – (blank)
    – Bacterial infection of the skin
    – (blank) 

    • CDC recommends that children be vaccinated with
    the _______ or Varivax vaccines at _____ months or
    before their ______ birthday
    300–400

    Pneumonia

    Encephalitis (swelling of the brain)

    MMRV measles mumps rubella varicella

    12–18 months

    13th
  38. Shingles or Herpes Zoster
    • After a primary VZV
    infection (chickenpox), the
    virus remains latent in the
    dorsal root ganglia
    (neurons of the nerve roots)
    • The virus is ___________
    • Risk of reactivation
    increases with age
    • Onset of shingles is more
    common and severe in
    immunocompromised
    patients
    most commonly reactivated later in life after the age of 60
  39. Symptoms of Shingles
    - Severe pain 
    - headache 
    (blank)
    - Itching
    (blank) 


    – Rash follows a nerve on one side of the body
    – In a healthy individual, disease lasts _____ days
    – Postherpetic neuralgia occurs in 1/5 with zoster and is characterized by severe pain that can continue long after the rash clears up
    – Disease lasts ______ weeks in an immunocompromised patient
    • - numbness
    • - Followed by a vesicular rash that forms in a 3- to 5- day period

    • 10–15 days
    • 3–4 weeks
  40. CMV Transmission
    • Via close, intimate contact with a person
    who is excreting virus in:
    – ______ 
    – ______
    – Other bodily fluids

    • It can be transmitted:
    – Sexually
    _________
    – Transplanted organs
    ________
    • saliva
    • Urine

    • – Through breast milk
    • – Blood transfusions
  41. CMV is the Most Important Cause
    of Congenital Infections
    • 1–3% of women infected during pregnancy
    in the U.S.

    • Developing, unborn babies (neonates) are
    at highest risk for developing
    complications of CMV infection
    – Hearing loss
    _________
    – Varying degrees of intellectual and
    developmental disabilities
    _________
    • – Visual impairment
    • – Motor problems
  42. _____ causes 79% of infectious mononucleosis

    _____ causes 21% of infectious mononucleosis
    Epstein-Barr Virus (Often referred to as the “kissing disease”)

    • Common infection throughout the world
    • • Vast majority of EBV infections occur in young children
    • and are asymptomatic
    • • Individuals infected with EBV during their teens or 20s
    • become symptomatic
    • • May be associated with MS lesions (see Virus File 11-2)
    • • In developing countries, EBV infection is associated with
    • Burkitt’s lymphoma (type of B-cell cancer in kids)
    • Incubation period ranges from 4–6 weeks

    cytomegalovirus
  43. Epstein-Barr Virus

    • Symptoms:
    – Sore throat
    (blank 1)
    (blank 2)
    – Malaise
    (blank 3)
    – Enlarged liver (sometimes)
    – Heart problems (rare)
    (blank 4)

    • Symptoms usually resolve within 1 or 2 months
    • – Fever
    • – Swollen lymph nodes
    • – Enlarged spleen (sometimes)
    • – CNS problems (rare)
  44. Mild disease in childhood that
    begins with sudden fever followed by a red rash
    Sixth disease (human herpes virus 6 causes this)
  45. Herpesvirus Life Cycle
    • Virus structure and classes of herpesviruses

    – Large (150–300 nm in diameter)
    – Enveloped (obtained via a double envelopment
    process)
    (blank 1)
    (blank 2)
    – Transmitted by direct contact with mucosal surfaces
    or secretions
    – Cannot be transmitted by toilet seats (or other
    inanimate objects) since herpesviruses dry out and
    become damaged when exposed to air
    – Pleomorphic particles

    – Fragile and easily disrupted by heat, desiccation(extreme dryness), 70% alcohol, soap, and detergents
  46. Herpesvirus Structure
    • what genome?
    • ______ kb pairs in length
    • More than ______ virally coded
    proteins
    • ________ capsid
    surround the core
    • Amorphous proteinaceous
    tegument surrounds the
    nucleocapsid (at least 8
    proteins)
    • Linear dsDNA
    • 125–229
    • 30
    • Icosahedral
  47. Classes of Viral Genes
    • 3 classes: Immediate-early (α), early (β), and
    late (γ)
    • Viral mRNAs are transcribed by the host’s RNA
    polymerase II inside the nucleus of the host cell
    • Viral VP16 protein activates the expression of
    the α genes
    – α genes encode DNA binding proteins that play a role
    in viral transcription of β genes
    – β genes encode DNA replication and additional viral
    transcription factors
    – γ genes encode the late structural proteins that are
    produced after viral genome replication has begun
    – Synthesized γ proteins are transported to the nucleus,
    where capsid assembly begins
    • Classes of Viral Genes
    • • 3 classes: Immediate-early (α), early (β), and
    • late (γ)
    • • Viral mRNAs are transcribed by the host’s RNA
    • polymerase II inside the nucleus of the host cell
    • • Viral VP16 protein activates the expression of
    • the α genes
    • – α genes encode DNA binding proteins that play a role
    • in viral transcription of β genes
    • – β genes encode DNA replication and additional viral
    • transcription factors
    • – γ genes encode the late structural proteins that are
    • produced after viral genome replication has begun
    • – Synthesized γ proteins are transported to the nucleus,
    • where capsid assembly begins
  48. genes expressed in latency that may prevent apoptosis in neurons
    Latency-associated transcripts (LATS)
  49. • Most commonly prescribed for HSV-1, HSV-2, VZV
    • Guanosine analog (ACG)
    • Converted 200x more efficiently to ACGmonophosphate
    by herpesvirus thymidine kinase
    (TK) than the cellular TK
    • Acts as a chain terminator (prevents DNA
    elongation)
    • Relatively nontoxic
    • Can be used for long-term prophylaxis
    • Can be administered topically to the skin or eye,
    intravenous or orally
    Acyclovir
  50. Diet and Herpesvirus Infection?
    • Foods high in _____ increase outbreaks
    • Foods rich in ______ reduce occurrence,
    severity, and healing time
    L-arginine

    • L-lysine (beef, chicken, fish, lamb, milk,
    • cheese, beans, brewer’s yeast, and most fruits
    • and vegetables)
  51. Chickenpox vaccine is a ______ Oka strain
    live attenuated
  52. Results of Department of Veteran Affairs
    Shingles Prevention Study: Varivax vaccine
    reduced shingles cases by _______

    • 2006: New vaccine, _______, approved by the FDA to reduce the risk of shingles in
    people 60 years of age or older
    51.3%

    Zostavax (Merck)
  53. Developing a CMV vaccine is a top priority
    for several reasons:
    – CMV infection is a major disease of the
    _______

    – CMV infection is the leading cause of _______ and ______ damage in children

    • A _______ vaccine containing CMV genes is being investigated in clinical
    trial
    immunocompromised

    inner ear (cochlea) hearing loss

    nervous system

    recombinant canarypox
  54. The Use of Genetically
    Engineered HSV to Treat Brain Tumors
    • 30% of brain tumors
    are malignant gliomas
    • Patients with malignant
    gliomas are ideal
    candidates for novel
    molecular-based
    therapies because:

    ________
    – MRI studies are
    available to monitor
    the outcome
    _______
    – Metastases are rare


    – Viruses provide a delivery technique that can target the tumor
  55. According to the latest figures from the World Health Organization, about
    40 million people worldwide are living with HIV/AIDS. In the U.S., about 1
    million are living with the virus, and 1 in 7 of those infected don't know it.
    • According to the latest figures from the World Health Organization, about
    • 40 million people worldwide are living with HIV/AIDS. In the U.S., about 1
    • million are living with the virus, and 1 in 7 of those infected don't know it.
  56. • HIV is present in (name 6)
    • blood
    • saliva
    • tears
    • vaginal fluid
    • semen
    • breast milk
  57. Most common ways HIV can be transmitted:

    (blank)
    – Sharing of contaminated needles (IV drug users)
    (blank)
    – Accidental needlestick injuries
    (blank)
    – Sharing HIV-contaminated tattoo needles, razors,
    acupuncture needles, ear-piercing implements
    • – Anal and vaginal intercourse
    • – Blood transfusions (using infected blood or blood products)
    • – Congenital AIDS


    (premastication and organ transplants are RARE to contract HIV)
  58. Prevention of HIV Infection
    • Abstinence from sex
    • Use of barrier methods (e.g., condoms)
    during sexual activity
    • Microbicides (e.g., intravaginal 1%
    tenofovir gel before and after
    intercourse)(blank)
    • Pre-exposure prophylaxis (PREP)
    • Postexposure prophylaxis (PEP): 4-week
    program
    #1 women
  59. Reasons that HIV patients who are not receiving
    treatment are left behind:
    (blank)
    – Inequalities in access to treatment and services
    – Gender-based inequalities
    (blank)
    – Human-rights violations, stigma, and discrimination


    – Criminalization and exclusion
  60. Put in order of most people with HIV

    India
    South Africa
    Nigeria
    • S. Africa
    • Nigeria
    • India
  61. HIV infection rate is ____ times higher among
    prison inmates than for the general population

    • Activities in prisons that pose a risk for HIV
    transmission:
    (Blank)
    – Intravenous drug use
    (blank)
    – Sharing of toothbrushes and shaving equipment
    (blank)
    5−7

    • – Homosexual activity
    • – Tattooing and body piercing
    • – Incidents of violence
  62. What disease leads to these issues?

    Wasting syndrome is also common (a loss of more
    than 10% of body weight due to fever or diarrhea for
    more than 30 days)

    non-Hodgkin’s lymphoma


    CD4+ TH lymphocyte cell count
    below 200 cells/μL of blood and/or one or more
    opportunistic infections
    AIDS
  63. HIV Virion Structure

    HIV genome?

    100 nm icosahedron-shaped sphere surrounded by an envelope
    • Envelope contains glycoproteins ______ and ________
    spikes
    • Matrix proteins located ______ the envelope

    _______ and ______bound to viral genome

    • ______ also found within nucleocapsid HIV
    +ssRNA

    • gp120
    • gp41

    below

    • Reverse transcriptase (RT; p64)
    • integrase (p34)
    • Protease (p10)
  64. Coreceptor on T lymphocytes:  

     Coreceptor on macrophages:
    CXCR4 (fusion)

    CCR5
  65. HIV-1 _____ and _____ regulate gene
    expression
    tat - early regulatory protein

    rev - early regulatory protein
  66. HIV-1 Assembly
    • HIV-1 virion components (e.g., the viral
    RNA, ____, ____, and _____ proteins) are
    assembled at budding sites located at the
    cellular plasma membrane
    gag - structural protein

    pol - structural protein

    env - structural protein
  67. HIV enters cell by binding to CD4 receptor and a co-receptor either CCR5-macrophage or CXCR4-t-cell and fuses and enters cell and brings its reverse transcriptase with it. It then transcribes a DNA strand, degrades the RNA, and synthesizes a second DNA strand. The double strand then enters nucleus through nuclear pore and integrates into the host cell DNA genome and transcribes viral RNA, then in cytoplasm translates viral proteins go to host cell membrane and assemble then bud and release from cell through lyses.
    HIV enters cell by binding to CD4 receptor and a co-receptor either CCR5-macrophage or CXCR4-t-cell and fuses and enters cell and brings its reverse transcriptase with it. It then transcribes a DNA strand, degrades the RNA, and synthesizes a second DNA strand. The double strand then enters nucleus through nuclear pore and integrates into the host cell DNA genome and transcribes viral RNA, then in cytoplasm translates viral proteins go to host cell membrane and assemble then bud and release from cell through lyses.
  68. The rare CCR5Δ32 allele led to increased
    survival during smallpox outbreaks in 14th century Europe
  69. Measure HIV-1 RNA copies per ml of plasma
    • ______ copies per ml of plasma = clinical AIDS

    CD4+ T lymphocyte counts
    – Less than 200 per µl plasma
    100,000
  70. HIV Antiviral Therapy
    • Zidovudine (AZT), a _______, RT
    inhibitor first approved HIV-1 treatment
    thymine analog
  71. Use of at least 3 compounds to jointly block HIV replication by
    inhibiting the viral protease and/or reverse
    transcriptase of HIV
    Antiretroviral therapy (ART):
  72. Put these in order of greatest to least amount of rabies animal reservoirs in the U.S.

    Fox
    skunk
    raccoon
    bat
    • Raccoon
    • Skunk
    • Bat
    • Fox
  73. Human Rabies
    • WHO estimates over 10 million people
    receive postexposure prophylaxis (PEP)
    annually
    • More than ____ rabies-related deaths
    each year, or ____ each day

    • Significant public health problem in _____
    55,000

    150

    China
  74. characterized by extreme
    behavioral changes, including overt aggression and attack behavior.
    – Furious rabies (encephalitic)
  75. characterized by weakness and loss of coordination, followed
    by paralysis.
    Paralytic rabies (or dumb)
  76. Rabies symptoms

    Symptoms During Prodromal Period
    • Headache
    (blank)
    • Fever
    (blank)
    • Nausea
    • Vomiting
    • Anorexia

    • Malaise
  77. Secondary Symptoms of Furious Rabies

    • Hydrophobia
    (blank)
    • Agitation
    (blank)
    (blank)
    • Hypersalivation
    • Bizarre behavior
    • Biting
    (blank)
    • Jerky and violent contractions of the diaphragm

    • Difficulty swallowing

    • Anxiety

    • Hallucinations
  78. Secondary Symptoms of
    Paralytic Rabies
    • In humans:
    blank
    blank
    blank
    – Weakness and ascending paralysis
    • – Lack of hydrophobia
    • – Lack of hyperactivity
    • – Lack of seizures
  79. Symptoms of Rabies in Wild Animals

    • Furious rabies: Excitation and aggressiveness, biting of objects, other animals, humans, or oneself

    • Dumb rabies:
    blank
    – Drooling and salivation (often choke to death)
    blank
    blank
    – Irritation around bite side (with frequent licking or biting)

    • Wildlife seem to lose fear of people, and nocturnal creatures may be out during daylight
    – Startled response to sudden noise or light

    – Reclusive behavior

    – Anorexia
  80. Rabies vaccine injection:

    – Dose: ______ shots injected
    intramuscularly into the forearm or shoulder
    on days 0, 7, 21, or 28
    – Usually takes 7–14 days to induce immunity
    – Immunity lasts approximately ______
    3 × 1-mL

    2 years
  81. What Should You Do if You Are Bitten by an Animal?

    • Provide the following information to a physician:

    – Animal involved
    blank
    – Vaccination status of the animal (if known)
    blank 
    blank
    – Whether the bite was provoked or unprovoked


    – Geographic location of the incident



    – Whether the animal can be safely captured for rabies testing
  82. Rabies bite animal 

    If the animal shows signs of rabies and can be captured, it will be euthanized and the head shipped to a qualified laboratory for testing
    If the animal shows signs of rabies and can be captured, it will be euthanized and the head shipped to a qualified laboratory for testing
  83. Postexposure Vaccination rabies:
     
    • 3 categories of vaccine:
    – Nerve tissue vaccines
    (blank)
    – Cell culture vaccines

    • Early vaccines made of nerve tissues
    – Produced serious side effects such as ______, Guillain-Barré−like syndrome, CNS disease, ________

    – ______ vaccine: 1 in 200 recipients experience serious neurological side effects, up to ______ mortality

    – Nerve tissue vaccines are still being used in ______, South America, and ______
    – Avian embryo vaccines

    paralysis

    meningoencephalitis

    Semple

    14%

    Asia

    Africa
  84. The Rabies Virus Replication Cycle

    • Classification:
    – Order: _______
    – Family: Rhabdoviridae
    – Genus: ______

    • Structure and properties
    – Unique ______ appearance
    – 75 nm diameter by 180 nm in length
    – Surface of the particle is covered with
    glycoprotein spikes
    – _____ protein inside of particle
    – ______ core  

    • Genomic RNA tightly encased by N, P, and L proteins
    Mononegavirales

    Lyssavirus

    bullet-shaped

    Matrix (M)

    Ribonucleoprotein
  85. RABIES

    • Genome consists of 11,932 nucleotides
    • What genome? 
    • 5 genes and a remnant gene or
    pseudogene (Ψ)
    -ssRNA
  86. Rabies life cycle:

    After amplification in muscle cell its released into synaptic cleft to bind to nicotinic acetylcholine receptors

    1. Rabies virus attachment
    2. Entry into neuron
    3. ______
    4. ______

    5. Transcription (L (RNA-dependent RNA polymerase) begins to
    transcribe the viral genome
    – A separate +ssRNA transcript is generated for each
    viral gene
    – Each viral transcript is capped and polyadenylated by
    the viral L protein)

    6. Translation (N, P, M, and L mRNAs are translated by free
    ribosomes
    – G mRNAs are translated on membrane-bound
    ribosomes of the ER)

    7. _______
    8. Replication
    9. _______
    10. Release
    3. axonal retrograde transport

    4. uncoating - – M protein dissociates from the RNP during uncoating

    7. Processing of G via ER and golgi (glycosylated)

    9. assembly
  87. A new or recently
    identified virus to humans
    Emerging virus
  88. A virus under control
    from a public health perspective but is
    making a comeback or reappearance, and
    increasing in incidence and geographical
    range of exposed human populations
    Reemerging virus
  89. Higher population densities favor the spread of
    viral diseases:
    – Crowding
    blank
    – Contamination of drinking water
    blank


    Human demographics drive viral disease
    emergence more than virus evolution or ecological factors (_____, race/ethnicity, ______, occupation, etc.)
    – Sanitation

    – Healthcare facilities

    sex/gender

    mobility/travel
  90. Increase in gastrointestinal illness caused by
    norovirus 10-fold between 2001 and 2004 on cruises

    –  blank
    – blank
    – Hard to determine the ______ in the virus that trigger more severe outbreaks
    Noroviruses cannot be cultured in the lab

    No animal model for noroviruses

    genetic changes
  91. Close proximity of wildlife to humans may
    contribute to viruses crossing the species barrier

    blank
    – Free range farming in Asia
    blank
    – Bushmeat in Africa
    – Monkeypox, U.S. exotic pet trading (prairie dogs)

    – “Wild taste”—Chinese delicacy from wild animals
  92. Viral Hemorrhagic Septicemia (VHS) Virus

    • Serious pathogen of fresh and saltwater fish
    • Emerging disease in the Great Lakes region of the U.S. and Canada


    • Infected fish show signs of:

    – Bulging eyes
    blank
    blank
    – Inactive or overactive behavior
    – Bloated abdomens

    – Hemorrhaging in the eyes, gills, skin, and the base of the fins
  93. Porcine Reproductive and
    Respiratory Syndrome (PRRS)

    Also called _______

    • Economically significant disease: Pork shortage
    • The virus attacks ______, crippling the
    animals’ immune system (allows viruses and
    other pathogens to do damage; e.g., severe
    pneumonia)
    • ______ strain is particularly virulent
    • Virologists are concerned that this virus may
    cross the species barrier from pigs to humans
    “Blue-ear pig disease”

    macrophages

    China
  94. Metagenomic survey results: ______ found in 25 of 30 Colony Collapse Disorder hives and only 1 healthy hive

    2010: Researchers detected a virus and fungus co-infection to cause CCD
    blank and blank
    Israeli acute paralysis virus (IAPV)

    • – Invertebrate iridescent virus-6 (IIV-6)
    • – Nosema ceranae
  95. Medical Practices and Susceptibility
    to Infection

    • Health-related infections:

    – Unsafe medical practices (e.g., reusing
    syringes and overuse of antimicrobials)
    blank
    – Poor hospital practices
    blank
    blank
    • – Xenotransplantation
    • – Immunosuppression
    • – Blood transfusions
  96. Use of immunosuppressive drugs used
    during organ or bone marrow transplants
    – Kidney dialysis
    blank
    – Chemotherapy
    – Chronic corticosteroid treatment
  97. Viral Infections in
    Immunocompromised Individuals

    blank 
    • Varicella zoster
    (causes chickenpox
    and shingles)
    • Herpes simplex
    virus
    blank
    • Human herpesvirus
    type 6
    • Human herpesvirus
    type 7
    blank
    blank
    • • Human cytomegalovirus
    • • Epstein-Barr virus
    • • Adenoviruses
    • • Hepatitis viruses
  98. About ______% of human
    cancers are associated
    with viruses
    20%
  99. • Cancer has afflicted
    humans throughout
    history

    blank 
    – Hippocrates observed
    carcinomas
    blank
    – Reims, France, first
    cancer hospital
    – Fossilized bone tumors mummies in Egypt

    – Chimney sweeps and scrotal cancer
  100. Early Cancer Research on
    Rous Sarcoma Virus (RSV)
    • 1908: _____ and _____ 
    demonstrated that _______ could
    produce tumors in chickens

    • 1911: ______ demonstrated a
    bacteria-free _____ caused sarcomas in
    chickens
    – The agent was Rous sarcoma virus, a
    retrovirus
    Wilhelm Ellerman and Olaf Bang

    Peyton Rous

    “filterable agents”

    filtrate
  101. ______ and ______
    • Discovered that the
    src gene of Rous Sarcoma Virus is
    found in the normal
    DNA of chickens
    • Their work
    demonstrated that
    oncogenes are
    cellular genes that
    were hijacked by
    viruses from cells

    who?
    Michael J. Bishop and Harold E. Varmus
  102. • At least 6 viruses are thought to contribute to
    10% of cancers
    • They are:

    – Hepatitis B virus (HBV)
    – Hepatitis C virus (HCV)
    blank
    blank
    – Kaposi’s sarcoma–associated herpesvirus (human herpesvirus 8)
    blank
    • – Human papillomavirus (HPV)
    • – Human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2)
    • – Epstein-Barr virus (EBV)
  103. A gene that has the potential to
    convert a normal cell to a cancerous or
    transformed cell
    Oncogene
  104. A viral gene responsible for the oncogenicity of the virus

    – Retroviruses may carry altered cellular genes that are tumor promoters
    Viral oncogene
  105. Cellular genes that promote
    the normal growth and division of cells
    Proto-oncogene
  106. Genes that suppress or inhibit the conversion of a normal cell into a cancer cell

    – These genes cause cancer when they are turned off
    Tumor suppressor genes
  107. The change in the morphological, biochemical, or growth properties of a cell
    Cell transformation
  108. A term for diseases in which abnormal
    cells divide without control
    Cancer
  109. When a cell or clump of cells separates from a tumor and spreads to another location
    Metastasis
  110. Characteristics of Cancer Cells (in vitro)

    • Genetic changes: Polyploidy (Polyploid cells and organisms are those containing more than two paired (homologous) sets of chromosomes. triploid, tetraploid), high levels of telomerases
    blank
    • Metabolic changes: Grow rapidly
    blank
    • Anchorage independent: Loss of adhesion
    • Require less serum in medium to grow
    blank
    • Changes in membrane structure and function
    blank
    • • Immortalization
    • • Lack of contact inhibition: Cells pile up
    • • Loss of cell cycle control
    • • Tumor-associated carbohydrate antigens
  111. Characteristics of
    Cancer Cells (in vivo)

    blank
    • Loss of tumor suppressor gene function
    blank
    • Increased or unregulated level of growth factors
    • Cells divide uncontrollably
    • Increased levels of enzymes involved in nucleic acid synthesis and lytic enzymes
    blank
    blank
    • • Increase in oncogene mRNA expression
    • • Changes in DNA methylation patterns
    • • Immune evasion
    • • Reactivation of telomerases
  112. Cancer is a Multistep Process
    blank
    • Cells circumvent the need for growth
    signals
    • Cells escape immunosurveillance
    blank
    blank
    • Tumor suppressor genes lose function
    • Cells (tumors) command their own blood supply

    • Cells may metastasize


    • Cells bypass apoptosis
  113. ____ gene encodes matrix and core proteins of the retrovirus that function to protect the viral ssRNA genome from damage
    gag
  114. _____ gene encodes a multifunctional protein that has
    reverse transcriptase, RNase H, helicase, and
    integrase activities
    pol
  115. _____ gene codes for a protein that is embedded
    within a lipid bilayer that surrounds the nucleoprotein
    core particle of the retrovirus
    env
  116. _____ gene codes a protein that induces cellular
    transformation (not essential in viral replication)
    v-onc
  117. Human Endogenous Retroviruses
    (HERVs)
    • _____% of the human genome consists of
    HERVs
    • Most sequences are defective and
    incapable of producing functional protein
    • Possible cofactor in _____, autoimmunity,
    and ______
    8%

    cancer

    schizophrenia
  118. DNA tumor viruses differ from RNA tumor
    viruses in that the _______
    v-oncs of DNA tumor viruses are essential viral genes used in replication
  119. • DNA tumor viruses target the ____ and p53
    tumor suppressor gene products of the host
    Retinoblastoma protein
  120. Burkitt’s Lymphoma

    • _____ gene moves near the immunoglobulin
    heavy chain or light chain gene
    – Abnormal expression of the _____ gene and increased tumorigenicity of the cells
    c-myc
  121. Papillomavirus Structure
    and Genome
    • Small (52–55 nm in
    diameter)
    • Nonenveloped
    • Icosahedralshaped
    genome?
    • Circular dsDNA genome (~8000 bp in length)
  122. HPV

    What keratinocyte differentiation stage layer?

    virion assmbly
    late capsid proteins L1 and L2
    vegetative DNA amplification
    - high levels of early and differentiated proteins , notably E4
    - koliocytosis of productive keratinocytes
    upper spinous layers
  123. HPV

    What keratinocyte differentiation stage layer?

    differentiation-dependent E6 and 57 proteins 

    early proteins E1 E2 E4 E5
    LOWER spinous layers
  124. HPV

    What keratinocyte differentiation stage layer?

    possible alternative site of infection 

    immediate early proteins E1 E2 and E5
    transit amplifying cells
  125. HPV

    What keratinocyte differentiation stage layer?

    establishment replication
    immediate early proteins E1 E2 E5
    Primary infection
    basal stem and reserve cells
  126. Adenovirus Structure
    • 80 nm in diameter
    • Icosahedral-shaped
    • Knobbed penton
    fibers

    genome? 

    • Can infect a wide
    variety of cell types

    blank
    • dsDNA (36–38 kb in length)

    – Chosen as a gene therapy vector
  127. Simian Virus 40 (SV-40)
    • Isolated from ______ by B.H. Sweet and
    M.R. Hilleman during safety testing of the
    ______ vaccine in 1960
    • Did not cause cytopathogenic effect
    • Frequent contaminant of rhesus monkey
    kidney cell culture cells
    • SV-40 is a ______
    primary African green monkey kidney cells

    poliovirus

    polyomavirus
  128. Simian Virus 40 characteristics

    • Small (45 nm in diameter)
    • Nonenveloped
    • Icosahedral-shaped
    • Three capsid proteins (VP1, VP2, VP3)
    genome?
    – 2 sets of genes (expressed early and late)
    – Origin of replications (ORIs)
    – Promoters
    – Enhancer sequences
    • Large and small T-antigens and 17kT antigen
    • dsDNA genome (5.2 kb in length)
  129. Cancer Therapy:
    The Last 150 Years
    blank
    • Radiation therapy
    • Chemotherapy
    – Mustard gas
    – Aminopterin (folic
    acid antagonist)
    blank
    • Surgery

    • Immunotherapy
  130. Believed that oncolytic viruses cause tumor cells
    to die in 4 main ways:
    – Infecting and replicating in cancer cells
    blank
    – Inducing lysis of cancer cell and expulsion of virus particles
    blank
    – Complicated mechanism such as stimulating the host’s immune system

    – Induction of apoptosis
  131. Challenges of Virotherapy
    • Immunity
    • Delivery
    blank
    • Biomarkers to track progress
  132. Infectious proteins that cause a group of
    diseases of the brain and nervous system called
    transmissible spongiform encephalopathies
    (TSEs)
    Prions
  133. Small, pathogenic RNAs that cause
    virus-like diseases in plants
    Viroids
  134. ______ cause a noninflammatory process that results in the vacuolation, or spongiosis, in the gray matter of the brain
    transmissible spongiform encephalopathies
  135. Kuru -cannibal 

    3 Stages of Symptoms

    • _____ stage: Unsteady gait, voice, hands, and eyes; tremors and shivering; slurred speech; loss of coordination in lower extremities

    • _____ stage: Patients could no longer walk
    without support; increased severity of tremors and coordination problems; jerky movements; outbursts of laughter, depression, mental slowing

    • _____ stage: Patients could not sit without
    support; increased tremors and speech slurring; incontinence; difficulty swallowing; deep ulcerations
    Ambulant

    Sedentary

    Terminal
  136. • Practice of eating dead relatives
    Endocannibalism
  137. Tissues, infectious waste, and instruments
    used in the processing of prion contaminated samples are decontaminated in:
    – 1 N NaOH or undiluted fresh household bleach followed by autoclaving at 132°C for 4.5 hours
  138. The normal cellular form proteinaceous infectious particle is the normal form abundant in neurons but post-translational misfolding occurs to get it to be a Proteinacous infectious particle resistant to protease digestion and this forms into clumps that damage nerve cells of brain
    Protein only hypothesis for infectious prions
  139. Hypothetical Model: PrPC
    Involvement in Secretory Pathway

    1. Proteinacous infectious particle cellular form is synthesized on rough ER

    2. __________

    3. PrPc cycled from the membrane into endocytic vesicles

    4. PrPc is either degraded or moves back to cell surface to bind to copper

    5. ________
    PrPc moves to plasma membrane via golgi secretory pathway to bind to copper

    Folding of PrPc to convert it to PrPres accumulation of fibrils
  140. – Signal transduction
    – Cellular differentiation
    – Cell adhesion
    – Copper transport
    – Resistance to the accumulation of destructive free radicals that can
    result in neuronal death
    PrPC possible functions
  141. The Three Ways That
    TSEs Can Arise
    • Infection
    – Diet, variant Creutzfeldt-Jakob disease (CJD), endocannibalism
    – Iatrogenic means (e.g., surgery)
    – Growth hormone injections
    – Corneal transplants
    • Inherited
    – Genetic CJD
    – Gerstmann-Straussler-Scheinker disease (GSS)
    – Fatal familial insomnia (FFI)
    • Sporadic forms
    – CJD
    • The Three Ways That
    • TSEs Can Arise
    • • Infection
    • – Diet, variant Creutzfeldt-Jakob disease (CJD), endocannibalism
    • – Iatrogenic means (e.g., surgery)
    • – Growth hormone injections
    • – Corneal transplants
    • • Inherited
    • – Genetic CJD
    • – Gerstmann-Straussler-Scheinker disease (GSS)
    • – Fatal familial insomnia (FFI)
    • • Sporadic forms
    • – CJD
  142. Iatrogenic transmission of CJD
    blank
    blank
    – Contaminated neurosurgical instruments
    – Human growth hormone from CJD-infected donors
    blank

    • Blood-borne transmission (suspected)
    – Variant CJD agent can be detected in lymphoid tissues
    – Transmission of BSE to sheep by blood transfusion from asymptomatic, infected sheep to healthy sheep
    • – Corneal grafts from infected donor
    • – Contaminated deep EEG electrodes implanted into brain
    • – Patients who received dura mater grafts
  143. Creutzfeldt-Jakob disease

    _____% of variant CJD patients die before age 30

    – Average age at death is ____ years

    • Patients suffering from classic CJD die at an average of ____ years of age
    50%

    28

    68
  144. Creutzfeldt-Jakob disease (CJD),

    Initial symptoms

    progessions

    final symptoms
    • Initial symptoms:
    • – Anxiety
    • – Memory loss
    • – Mood changes
    • – Depression
    • – Withdrawal

    • Progression of CJD
    • • Neurological signs
    • – Twitching
    • – Spasms (jerky movements)
    • – Posture and gait abnormalities (motor difficulties)

    • • Final symptoms
    • – Loss of speech
    • – Stupor
    • – Coma
    • – Death 14 months after symptoms appear
  145. Diagnosis of Variant CJD
    • Prion-positive immunostaining of biopsy material
    – Tonsils, spleen, and lymph nodes
    blank
    • MRI
    blank
    • Gold standard: Postmortem examination of brain tissues
    – Western blot analysis
    – Immunocytochemistry of PrPres accumulation in brain
    tissues
    • EEG (slow or negative brainwave activity)

    • CSF testing for elevated levels of proteins
  146. Brain Changes of transmissible spongiform encephalapathies

    blank

    • Neuronal loss: Apoptosis

    • Astrocytosis: Spread of astrocytes to damaged tissues in the brain

    blank
    • Spongiform changes: Vacuoles (clear zones) similar to a sponge

    • Amyloid plaques: Formation of PrPres threadlike aggregates
  147. Chronic Wasting Disease (CWD)
    • Prion disease of deer, elk, and moose
    • Symptoms include:

    blank
    – Excessive drooling and thirst
    blank
    – Aspiration pneumonia
    • 15% in free-ranging deer and >90% in captive deer herds

    • Transmission directly or indirectly (through feed or water sources)

    • Plants can act as carriers of prions and play a role in horizontal transmission of prion diseases
    – Emaciation- state of being abnormally thin or weak

    – Frequent urination
  148. Viroids: Small RNA molecules that infect
    plants in the same manner as conventional
    viruses

    blank genome?
    – Internal base-pairing
    blank
    blank
    – +ssRNA, covalently closed circular pathogenic molecules

    – Depend upon the plant host enzymes for their replication and other functions

    – Do not code for any proteins
  149. Two Families of Viroids
    • Avsunviroidae:
    – Branched, “quasi” rodlike structure
    – Accumulate and replicate in chloroplasts
    – Lack a C region
    • Pospiviroidae:
    – True, rodlike secondary structure
    – Nuclear localization
    • Viroids contain 5 structural or functional domains:
    – Central (C): Critical for replication and processing
    – Pathogenicity (P): Symptoms of viroid-infected plants
    – Variable (V): Highest variability in sequence
    – Two terminal domains (T1 and T2): Role in viral movement
    • Two Families of Viroids 
    • • Avsunviroidae: 
    • – Branched, “quasi” rodlike structure 
    • – Accumulate and replicate in chloroplasts 
    • – Lack a C region 
    • • Pospiviroidae: 
    • – True, rodlike secondary structure 
    • – Nuclear localization 
    • • Viroids contain 5 structural or functional domains: 
    • – Central (C): Critical for replication and processing 
    • – Pathogenicity (P): Symptoms of viroid-infected plants 
    • – Variable (V): Highest variability in sequence 
    • – Two terminal domains (T1 and T2): Role in viral movement
  150. Viroids Do not replicate in the cytoplasm like
    conventional plant RNA viruses

    they replicate in the _____ or _____ of the plant
    nucleus or chloroplast
  151. • The cell’s _____-dependent RNA
    polymerase ____ synthesizes viroid RNA
    DNA

    3
  152. Localization of Viroid ssRNAs
    • Viroid ssRNAs of positive polarity localize to
    the _____ and _____ of host cells
    • Viroid –ssRNA are localized only to the
    _______
    nucleolus

    nucleoplasm

    nucleoplasm
  153. First viroid
    characterized in 1971
    Potato Spindle Tuber Viroid
  154. Viroid Pathogenesis
    • Viroids activate a plant ______
    dsRNA-activated protein kinase (PKR)
  155. The only DNA retro virus

    DNA -> RNA -> DNA
    Hepatitis B
  156. only + sense RNA virus whose genome is replicated by the host
    HIV
Author
JAM41MAN
ID
339667
Card Set
Virology exam 3
Description
viro
Updated