Rabies, Prion disease and Herpes Flashcards

(51 cards)

1
Q

Why is rabies a more common cause of death in the developing world?

A

more exposure to animals

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2
Q

What group of viruses is rabies included in?

A

rhabdovirus, subtype lyssavirus

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3
Q

What are the key proteins in rabies virus?

A

viral glycoprotein/envelope (G)
nucleocapside (N)
matrix (M)
NS and L proteins rarer

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4
Q

What type of genome does rabies have?

A
  • ss RNA
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5
Q

What can envelope (G) bind?

A

nicotinic ACh receptor in muscle, gangioside and CD56 in neurons

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6
Q

How does rabies virus enter cells?

A

is endocytosed and envelope fuses at low pH with endosomal membranes to release nucleoprotein

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7
Q

What switch must occur in order for rabies genome production to occur?

A

viral polymerase switches from mRNA mode to making full length + RNA which will serve as a template for - genome production
due to a buildup of N protein

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8
Q

Does rhabdovirus budding usually kill cells? Does it kill cells in the case of rabies?

A

yes

no

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9
Q

Which rabies molecule eleicits neutralizing antibodies?

A

G glycoprotein
is not protective
allows for vaccine production

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10
Q

How does rabies typically enter the body?

A

through a wound or ski abrasion via a bite and introduction to infected saliva
-also, rarely via infected cornea/organ transplants

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11
Q

Where does virus replicate during the “incubation” period?

A

muscle or connective tissue

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12
Q

How quickly does rabies virus travel in the CNS?

A

8-20mm/day

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13
Q

When is rabies intervention effective?

A

before spread to the nerves/CNS

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14
Q

Where does the rabies virus disseminate to after replicating in high levels in the brain?

A

eye, salivary glands, innervated ski (ie/hair follicles)

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15
Q

How long does the incubation period usually last?

A

3-8wks
patients usually asymptomatic
*the closer a bite is to the brain the shorter this period

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16
Q

What is the prodrome phase of rabies infectioin?

A

early after infection of brain
nervousness, headache, anxiety, pain at bite site, fever, nausea
progresses to myoclonus, slurred speech and tingling
presents to brain at end of this period, patients usually still Ab negative

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17
Q

Describe the acute neurological phase of rabies infection

A

high virus titer in brain and elsewhere
Ab present in serum and CNS
Progression from here can be “furious”/fulminant, or “dumb”/paralytic

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18
Q

Describe furious/fulminant progression of rabies

A

classic rabies
bizarre behavior, hallucinations, seizures, hydrophobia
fury later gives way to paralysis, then either coma or sudden fatal cardiac or respiratory arrest

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19
Q

Descirbe the paralytic or dumb progression of rabies

A

ascending flaccid paralysis, leads to fatal paralysis of respiratory muscles

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20
Q

What is the “hydrophobia” associated with rabies?

A

violent spasms of respiratory muscles triggered by drinking water
sight sound or mention of water can trigger it

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21
Q

What are “negri bodies”?

A

virus vactories, seen in some but not all cases of rabies

22
Q

What is Dr. Wiloughby’s theory on the pathology of rabies?

A

that it is a metabolic disease
(a disease of ‘software’, not ‘hardware)
based on observation that patient’s brains are normal on gross path, there are Abs during final acute phase, and there is often little virus remaining at end stages

23
Q

How is rabies diagnosed?

A

neurologic sx in living person w/suspected exposure

confirmed by detecting virus in CSF, saliva, skin or PCR

24
Q

How are animals tested for rabies?

A

brain tissue tested by dFA

25
How is rabies prevented?
immunization of domestic animals and high risk individuals (ie/vets)
26
What is post-exposure prophylaxis protocol?
passive immunization-Ig introduced into wound area and IM, keeps virus 'local' active immunization-human diploid cell vaccine of killed virus, 4-5 doses this should be initiated ASAP after exposure
27
Which wild animals most commonly lead to rabies exposure in the US?
raccoons, bats, skunks, foxes
28
How are most cases imported into the US?
tourest exposure outside the US, often via dog bites
29
List some animal prion diseases
Scrapie-sheep/goats BSE/madcow CWD
30
What are the human prion diseases?
``` Kuru (ritualistic cannibalism assoc.) CJD variant CJD Gerstemann-Straussler-Scheinker disease Fatal Familial insomnia ```
31
What prions?
unconventional virus like agents | a proteinacious infectious particle
32
What are the symptoms of Creutzfeldt Jakob disease?
progressive dementia leading to ataxia, paralysis, wasting and death (usually via pneumonia) within 6mo of onset
33
What are the origins of Creutzfeldt Jakob disease?
sporadic, in older individuals, thought to be spontaneous change in prion protein to a pathologic form familial/genetic-dominantly inherited transmitted via contaminated GH inj, corneal transplant, or electrode implants
34
How is vCHD contracted?
via consumption of BSE contaminated beef
35
How is Gerstemann-Straussler-Scheinker disease contracted?
familial CJD inherited PrP mutation illness evolves more slowly (3-5yr)
36
Describe fatal familial insomnia
inherited PrP mutation, causes sleep problems leading to ataxia and death
37
What does histology look like in a prion disease?
vacuolization in neurons, gives a spongiform appearance in grey matter soemtimes amyloid plaques or tangles
38
How long does it take to go from prion infection to symptoms?
long incubation, takes months-decades for sx to appear
39
What type of immune response is generated by prion disease?
no response of any kind
40
How are prion diseases diagnosed?
based on clinical grounds
41
How are prion disease treated?
no treatments | careful disinfection of medical instruments important when prion disease suspected
42
What normal cellular gene encodes for prion protein?
PRNP, encodes PrPc
43
What change in PrPc occurs in prion disease?
alpha helical sturcutre to insoluble beta sheet form (PrPsc)
44
How is PrPsc 'replicated'?
pathologic form recruits or converts normal protein to adupt the PrPsc shape
45
What type of genome do herpes viruses have?
linease dsDNA
46
Where does herpes replicate?
in the nucleus
47
How are herpes infections maintained in the latent lifecycle?
as an episome
48
What happens with herpes infections are reactivated?
virion components are transported within a peripheral axon in anterograde manner such that infectious virions are released at or close to the site of original inoculation hwere lesions can again appear can also lead to retrograde transport to CNS, where serious encephalitis results
49
Where does herpes encephalitis usually occur?
one of the temporal lobes
50
What are symptoms of herpes encephalitis?
seizures, focal neuro abnormalities, other features of viral encephalitis
51
How is HSV infection treated?
acyclovir and derivatives inhibit viral DNA pol but not cellular DNA pol viral TK phosphorylates acyclovir and incorporates is like dGTP, resulting in chain termination cellular kinases convert to triphosphate, VIRAL pol inhibited