Prions and DNA Viruses I and II Flashcards

(51 cards)

1
Q

Prion Disease: General

what is the incubation period? why are they hard to study?

A
  1. caused by aberrant infectious protiens
  2. can incubate long periods of time (30 yrs- hence they are difficult to study)

No genome or immune response is involved. Rather, misfolding and protein aggregation caused tissue stress, particularly to the NS.

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2
Q

PRP C

what does it do, size, structure?

which chromosome

A
  1. Normal protein= PRP C
  2. 27-30 kDa membrane glyocprotein)
  3. Protease Sensitive, alpha helical, ch. 20
  4. MODULATES K channels in brain

PRP SC is proteinase resistant

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3
Q

PRP SC

what is ti resistant to? what does it polymerize into?

A
  • resistant to heat, disinfectants, radiation
  • mostly B-sheets that aggregate into amyloid rods (fibrils)
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4
Q

Creutzafeldt-Jakob Disease

Three types of cause?

A

Causes
1. Sporadic (90%)- peak in 6th decade of life
2. Genetic (10%)- Fatal Familial Insomnia and Gerstmann–Sträussler–Scheinker syndrome (SSS)
3. Acquired (1%)- Kuru (person to person) and CJD and vCJD

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5
Q

Gerstmann–Sträussler–Scheinker syndrome

A
  • prions in the cerebellum
  • symptoms: ataxia, incoordination
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6
Q

Fatal Familial Insomnia

A
  • genetic cause
  • progressively worse insomnia
  • prions build up primarily in the thalamus
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7
Q

Kuru

A
  • means “to shiver”
  • symptoms: loss of coordination, muscle twitching, dementia
  • spread of cannabalism
  • erosion of the cerebellum
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8
Q

Prion Disease Pathogenesis

A

Three different pathways:
1. sporadic
2. hereditary
3. acquired

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9
Q

General Characteristics of Human Prion Diseases

Transmissible spongiform encephalopathies

VCJD

A
  1. slow degenerative disease
  2. spongiform accumulation in brain
  3. symptoms take decades to appear but once they appear, death is rapid.
    4.mean age- 68 yrs (adult); vCJD younger but >14 yrs (avg is 28 yrs)

vCJD - shorter incubation & rapid progression (mean age - 28y)

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10
Q

vCJD

A

variant CJD- bovine transmission

shorter incubation & rapid progression (mean age - 28y)

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11
Q

fCJD

A
  • inherited form of CJD (mutation in prion gene)
  • thalamus impacted

FFI is clinically characterized by alterations in the sleep–wake cycle causing progressive insomnia and dementia. It is associated with the D178N mutation in combination with methionine at codon 129. If the D178N mutation occurs in combination with valine at codon 129 then an fCJD phenotype manifests.

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12
Q

General Symptoms of HUman Prion Disease

A

● Rapidly developing dementia

● Difficulty walking and changes in gait

● Hallucinations

● Muscle stiffness

● Confusion

● Fatigue

● Difficulty speaking

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13
Q

Diagnosis of Prion Disease

A
  1. brain MRI shows amyloid in cerebellum
  2. prions accumulate in **tonsils **
  3. Elevated tau or 14-3-3 in CSF
  4. Western Blot biopsy of PRP SC in tonsil
  5. Real-time quaking-induced conversion (RT-QuIC) assay: incubate sample with normal PRP C and see if aggregates form- these are detected with fluorescent dyes, ELISA, etc.

14-3-3 proteins were originally discovered as a family of proteins that are highly expressed in the brain. Through interactions with a multitude of binding partners, 14-3-3 proteins impact many aspects of brain function including neural signaling, neuronal development and neuroprotection.

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14
Q

Real-time quaking-induced conversion (RT-QuIC) assay:

A

incubate sample with normal PRP C and see if aggregates form- these are detected with fluorescent dyes, ELISA, etc.

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15
Q

Parvoviruses

A
  • smallest DNA virus
  • Linear ss DNA
  • Naked
  • Icosahedral
  • B19 and Bocavirus
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16
Q

Bocavirus

A

a recent virus, can cause acute respiratory disease

Not a test answer

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17
Q

B19 Epidemiology

A
  1. childhood (4-15 yrs)
  2. late winter and spring
  3. respiratory droplet and oral secretions (need close contact
  4. Mother to Fetus during pregnancy
  5. very common (65% by 40)
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18
Q

B19 initial infection

A
  1. nasopharynx, then via viremia to BM
  2. target erythroid precursor cells that possess P antigens. ??
  3. leads to anemia (from cell lysis) and immune response (rash and arthralgia
  4. 4-12d incubation, mild prodrome (fever, myalgia, itching).

arthralgia- joint pain
myalgia-muscle aches and pain

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19
Q

B19 infection->Slapped-cheek syndrome

A
  1. AKA erythema infectiosum
  2. facial rash that spreads to body
  3. possible polyarthropathy

Polyarthropathy is more common in adults, especially women.

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20
Q

Hydrops Fetalis

A
  1. B19 Virus
  2. transplacental transmission
  3. fetal erythroid precursor cells and fetal tissues
  4. resulst in anemia
  5. may result in still birth
  6. extensive edema?

Diagnosis:
1. facial rash
2. serology
3. PCR.

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21
Q

serology

A

diagnostic examination of blood serum

22
Q

HPV- General Characteristics

A
  1. DS DNA
  2. Naked
  3. Icosahedral
  4. Transmitted by skin-to-skin contact & vaginal, anal, oral sex.
  5. lytic, chronic, latent & transforming infections.

DNA or RNA tumor viruses may mediate multiple changes that convert a normal cell into a malignant one. RNA tumor viruses usually transform cells to a malignant phenotype by integrating their own genetic material into the cellular genome and may also produce infectious progeny.

23
Q

HPV- Epidemiology

A
  1. most prevalent STI
24
Q

HPV biological effect

A
  • induces epithelial proliferation via inhibiting p53 and 105RB
  • leads to papillmoas (warts) in 1-6 months

CD8 cytotoxic T cells (CMI) cause the wart to regress.

25
Condylomata accuminata
* **Anogenital warts** * **HPV 6/11**
26
Head/Neck Tumors
**laryngeal tumors**-benign solitary tumors (**HPV 6/11**) ## Footnote May be serious in children infected at birth (may obstruct airway).
27
Cervical Dysplasia and Carcinoma
* HPV present in ~99.7% cervical cancers (**HPV-16/-18** in 70%). ## Footnote Gardasil-6, 11, 16, 18, 31, 33, 45, 52, and 58
28
HPV Diagnosis
1. DNA probes and PCR 2. Pap Tests- **koilocytes** ## Footnote kiloicytes-Cells with perinuclear haloes surrounding condensed nuclei.
29
koilocytes
30
Polyomaviruses
* very common- most individuals are seropositive by age 15 * disease mostly in immunocompromised (T Cell deficient individuals) * Enter the **RT** and infect **lymphocytes** and then the **kidney** **Hemorrhagic cystitis** is a medical condition that occurs when your urinary bladder lining becomes inflamed and bleeds ## Footnote LATENCY: BKV in **kidney**; JCV in **kidneys, bone marrow, tonsils**.
31
BK Virus
1. **Hemorrhagic cystitis **: hematopoietic stem cell transplant patients 2. **Polyomavirus-associated nephropathy**: Seen in patients 6 months after receiving renal allografts. 3. unilateral stenosis ## Footnote renal allograft- Hemorrhagic cystitis is a medical condition that occurs when your urinary bladder lining becomes inflamed and bleeds
32
JCV Diseases
1. widespread (exacerbated by AIDS and immunosuppressants) 2. oligodendrocyte destruction results in demyelination 3. **Progressive Multifocal Leukoencaphalopathy**
33
Progressive Multifocal Leukoencaphalopathy
1. quick onset with degeneration 2. symptoms: Clumsiness, weakness, personality changes, trouble speaking, and vision problems, etc
34
BKV and JCV: Diagnosis
1. PCR of CSF 2. brain imaging reveal **swollen oligodendrocytes** with nuclear inclusions 3. increased oligoclonal bands in CSF & blood. ## Footnote ??
35
Adenovirus: General Characteristics
1. naked 2. icosadeltahedral 3. DS DNA 5. own DNA Pol 5. fibers for attachment 6. resistant to **GI, drying, detergents**
36
Adenoviruses: How do they spread?
1. spread in aerosol, fecal matter, close contact, fingers to eyes. 2. swimming pools- inadequate Cl 3. Infects mucoepithelial cells in **RT, GIT, conjunctiva/cornea**. 4. Risk: less than 14 yrs, crowded living (military, day care) 5. serious respiratory infections in military recruits (Acute Respiratory Tract Disease) ## Footnote [https://www.webmd.com/children/adenovirus-infections]
37
Adenovirus Disease
1. Acute Febrile Pharyngitis 2. Pharyngoconjunctival Fever 3. Conjunctivitis (swimming pools) 4. Keratoconjunctivitis (industrial workers) 5. Acute Respiratory Tract Disease 6. Gastroenteritis and Diarrhea (particularly infants) ## Footnote pharyngitis- mimic strep throat (less than 3 years old) Pharyngoconjunctival fever in outbreaks - involves older children
38
Enteric Adenoviruses rarely cause?
respiratory tract symptoms and fever
39
Adenovirus Diagnosis
* Virus in throat of a patient with pharyngitis – diagnostic * presence of **nuclear inclusion bodies** * DNA & serological probes helpful * SPIKES IN EM ARE CONCLUSIVE
40
Herpesviridae structure
1. DS DNA 2. Enceloped- senstive to acids, detergents, drying 3. icosahedral capsid 4. tegument??
41
Herpesviridae types
42
Herpersviridae: new virions
* budding, lysis, cell to cell bridges
43
Herpes envelope and Immune Response
CMI important since Antibodies less effective against the enveloped Herpesviridae
44
Herpesviridae DNA Polymerase
error prone, target for retrovirals
45
Herpesviridae: Types of infections
lytic, persistent, latent (recurrent), & immortalizing infections.
46
HSV-1 and 2
HSV-1 first (90% of third world by age 2) distinguish with serological and molecular tests (similar homology and symptoms)
47
HSV-1 and HSV-2 Epidemiology
1. transmitted via infected lesions 2. mucoepithelial cells 3. no seasonal occurence 4. cell to cell spread and syncytia help avoid anitobodies 5. HSV-1 above waist, HSV-2 below, **generally**
48
HSV-1 and HSV-2 Pathogenesis
HSV-1 latent in **Trigeminal Ganglia**; reactivation more specific to** oral ** HSV-2 latent in **sacral ganglia**; reactivation to **genital areas** ## Footnote **stress, trauma, and UV** can reactivate latent virus virus travels down nerve and causes lesions (tingling and pain appear before these lesions. Also, these lesions are vesicular lesions that contain virions
49
HSV-1 and HSV-2 cross immunity
1. HSV-1 pre-infected may show mild HSV-2
50
Oral Herpes
**Herpes Labialis**/ **gingivostomatitis** 1. caused mostly by HSV-1 (sometimes HSV-2) 2. lesions on mouth, buccal mucosa, tongue 2. **primary herpes**- gingivostomatitis in kids, pharyngitis in adults
51
Herpetic Keratitis
1. mostly HSV-1 2. mostly one eye 3. leads to permanent scarring, corneal damage, blindness