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Flashcards in Viruses affecting the CNS Deck (58):
1

Define the terms neurotropic, neuroinvasive and neurovirulent?

Neurotropic: capable of replicating in nerve cells

Neuroinvasive: capable of entering or infecting the CNS

Neurovirulent: capable of causing disease within the CNS

2

What is myelitis?

Inflammation of the spinal cord

3

What is encephalomyelitis?

Inflammation of both the brain and spinal cord

4

What is the difference between primary viral encephalitis and secondary encephalitis?

Primary viral encephalitis (acute viral encephalitis): direct viral infection of spinal cord and brain

Secondary viral encephalitis (post-infectious encephalitis): viral spread to brain as a complication of a current viral infection 

5

Describe the general presentation of viral meningits?

Headache

Fever

Neck stiffness

Vomiting

Photophobia

6

What is the major cause of viral meningitis?

Enteroviruses

7

Describe the causes of viral meningitis, other than enteroviruses?

Mumps

Varicell-zoster

Influenza

HIV

Herpes simplex 2 (genital)

8

Describe the presentation of viral encephalitis?

Like meningitis, but followed by:

Personality and behavioural changes

Seizures

Partial paralysis

Hallucinations

Altered levels of consciousness

Coma and death

 

9

What is the major cause of viral encephalitis?

Herpes simplex virus types 1 and 2

Rabiesvirus

Arboviruses

Enteroviruses

10

Describe postinfectious encephalomyelitis?

Can occur a few days after in fection with measles, chickenpox, rubella or mumps

No virus present

Inflammation and demyelination

Possibly autoimmune (part of virus looks like myelin sheath)

11

Describe Guillain-Barre syndrome?

Acute inflammatory demyelinating disease

Following infection with EBV, CMV, HIV

Results in partial or total paralysis, but most people recover 

Does not require active infection 

12

Describe Reye's syndrome?

Occurs post-infection with influenza or chickenpox in children

Cerebral oedema, but no inflammation

Associated with administration of aspirin during initial fever 

13

Give an example of a chronic demyelinating disease?

Sub-acute sclerosing panencephalitis (SSPE)

Late sequel to measles infection (reason for vaccine - to avoid this)

Rare, due to measles vaccination 

14

By which mechanisms can viruses access the brain?

BBB provides protection against some viruses

If virus enters PNS or ganglia > travel via axon fibres to CNS

15

Describe how viruses move through the PNS to access the CNS?

Carried passively along axons or dendrites 

Anterograde or retrograde spread 

Can cross synaptic junctions 

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16

Why aren't viruses destroyed by the immune system as they travel through the PNS?

Protected from attach by CTL as nerve cells do not have class 1 molecules 

17

Where does viral replication take place in the nervous system? Why?

In the body, as this is where protein synthesis takes place

18

How can the viruses access the CNS, other than via the PNS?

Bloodstream (viremia)

Can occur via cerebral blood vessels, choroid plexus or memingeal blood vessels 

 

Olfactory bulb 

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19

Describe the various effects that viruses can have once they enter the brain?

Directly kill neurons > cause inflamamtory disease

Replicate in non-neuronal cells > cause demyelination

 

20

Describe the effect of inflammation on the blood brain barrier?

During inflamamtion, lymphocytes, antibodies and other immune effectors can enter (they are normally excluded) 

21

Describe the neuroinvasiveness and neurovirulence of rabiesvirus?

High neuroinvasiveness and high neurovirulence 

22

Does rabiesvirus require growth in nerve cells as part of its life cycle?

Yes 

23

Describe the morphology of the rabiesvirus?

Bullet shpaed

-ve stranded RNA

Helical capsid

Envelope 

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24

How does rabiesvirus exit nerve cells?

Budding (envelope)

25

Describe the pathogenesis of rabies?

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26

Describe the symptoms of rabies?

Aggression (biting)

Thirst, but muscle spasm and terror upon attempt to drink water 

27

Describe the time frame for infection with rabiesvirus?

Symptoms anywhere between 40 and 70 days after infection 

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28

Which is the only disease for which vaccination is helpful after infection?

Rabies

60 day window of opportunity to catch virus before it gets to brain and mount immune response 

29

Which viruses are alpha herpesviruses?

HSV 1 and 2

Varicella-zoster virus

30

Do the alpha herpesviruses require growth in nerve cells as part of their life cycle?

Yes

31

Describe the neuroinvasiveness and neurovirulence of alpha herpesviruses?

Low neuroinvasiveness

High neurovirulence

32

Describe the morphology of alpha herpesviruses?

Large

Linear dsDNA genome 

Icosahedral

Envelope 

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33

How do alpha herpesvirsues enter the body?

Via mucosal surfaces 

34

When does serious disease occur with alpha herpesviruses?

If virus moves from mucosal surface to blood and replicates (then enters brain and spinal cord) 

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35

Where do latent infections of alpha herpesviruses reside?

Sensory and autonomic ganglia

36

How is HSV1 transmitted?

Contact with infected saliva

37

Which body parts are usually implicated in primary infections with HSV1?

Mouth and/or throat

May be inapparent

Gingivomastitis in children 

38

Describe the pathogensis of HSV?

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39

What is the most dangeorus outocome of HSV infection?

Severe sporadic encephalitis

Infects neurons and glia in temporal lobe

40

What is the most common cause of severe sporadic encephalitis?

HSV infection

Usually reactivation of latent infection, not a primary infection 

41

Describe how HSV is maintained in a latent state?

Genome of HSV maintained in an episome coated with histones in ganglia

Maintained in latent state by immune mechanisms (CTLs kill HSV when it pops out)

42

What does HSV express in its latent state?

Latency activated mRNA transcripts (LATs)

43

How is varicella-zoster virus spread within the body?

During chickenpox - haematogenous spread

Susequently enters nerves to cause vesicular rashes 

44

Describe the pathogenesis of chickenpox?

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45

How can varicella-zoster virus become latent?

From the rash, can travel back up to DRG and become latent 

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46

What is shingles?

Reactivation of latent varicella-zoster virus

Painful blisters that follow a dermatome 

47

In which population does shingles most commonly occur?

Elderly (>55)

When CTL response starts to wane, and infection cannot be kept latent 

48

What type of virus is poliovirus?

Enterovirus

49

How is poliovirus spread?

Faecal-oral spread 

50

Does poliovirus require growth in nerve cells as part of its life cycle?

No

Occurs as an accident 

51

Describe the neuroinvasiveness and neurovirulence of poliovirus?

Low neuroinvasiveness

High neurovirulence 

52

Describe the morphology of poliovirus?

+ve RNA

Icosahedral capsid

NO envelope 

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53

Describe the effect that poliovirus has on the cells that it infects?

Cytocidal virus > kills cells in which it replicates 

54

How does poliovirus exit cells?

Kills cell that it is in so that it is released 

55

Describe the pathogenesis of poliovirus?

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56

Which cell types does poliovirus target? Why?

Anterior horn cells in spinal cord

These cells have receptor that virus can use to replicate 

57

Describe the outcome of infection with poliovirus?

Total paralysis within hours if it infects CNS

<1% is irreversible 

Lower lims affected more than upper limbs > acute flaccid paralysis

If trunk, thorax and abdomen affected > quadriplegia

Mortality rate 5-10% once respiratory muscles immobilised 

58

When do epidemics of enterovirus meningitis occur?

Summer/autumn