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MD1 Neuroscience > Viruses Affecting the Central Nervous System > Flashcards

Viruses Affecting the Central Nervous System Flashcards

1
Q

What is a neurotropic virus?

A

Capable of replicating in nerve cells

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2
Q

What is a neuroinvasive virus?

A

Capable of entering/infecting CNS

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3
Q

What is a neurovirulent virus?

A

Capable of causing disease within nervous system

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4
Q

What is encephalomyelitis?

A

Inflammation of brain and spinal cord

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5
Q

What is primary viral encephalitis/acute viral encephalitis?

A

Direct viral infection of spinal cord and brain

Can be focal or diffuse

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6
Q

What is secondary encephalitis/post-infectious encephalitis?

A

From complications of current viral infection

Virus spreads to brain

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7
Q

What is the most common route viruses take to the brain?

A

Blood

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8
Q

What is more common: viral or bacterial meningitis?

A

Viral

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9
Q

What is more severe: viral or bacterial meningitis?

A

Bacterial

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10
Q

What is the presentation of meningitis?

A 
Headache
Fever
Neck stiffness
\+/- vomiting
\+/- photophobia
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11
Q

What is the main viral cause of meningitis?

A

Enteroviruses

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12
Q

How do enteroviruses enter the body?

A

Via mouth

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13
Q

What are some other viral causes of meningitis, that aren’t enteroviruses?

A 
Mumps
VZV
Influenza
HIV
HSV 2
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14
Q

What is more severe: viral or bacterial encephalitis?

A

Viral

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15
Q

What is the presentation of encephalitis?

A

Like meningitis, but also

  • Personality and behavioural changes
  • Seizures
  • Partial paralysis
  • Hallucinations
  • Altered state of consciousness
  • Ultimately coma and death
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16
Q

What are the most common causes of viral encephalitis?

A

HSV 1 and 2
Rabiesvirus
Arboviruses (insect-borne)
Enteroviruses

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17
Q

Can mumps virus meningitis also cause encephalitis?

A

Yes but is generally mild

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18
Q

What is post-infectious encephalomyelitis?

A 
Occurs few days after infections
No virus present but
- Inflammation
- Demyelination
Possibly autoimmune in nature
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19
Q

Which viruses can cause post-infectious encephalomyelitis?

A

Measles
Chickenpox
Rubella
Mumps

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20
Q

What is Guillain-Barre syndrome?

A

Acute inflammatory demyelinating disease after infection with several viruses
Partial/total paralysis in 75% of people
Full recovery within weeks
Doesn’t need active infection

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21
Q

Which viruses can cause Guillain-Barre syndrome?

A

EBV
CMV
HIV

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22
Q

What is Reye’s syndrome?

A

Post-infection with influenza or chickenpox in children
25% case-fatality rate
Cerebral oedema but no inflammation
Association with administration of aspirin during initial fever

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23
Q

What are chronic demyelinating diseases?

A

Very rare
Eg: sub-acute sclerosing panencephalitis (SSPE)
- Late sequel (30 yrs) to measles infection

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24
Q

What is AIDS encephalopathy/AIDS dementia complex?

A

HIV infection > immunodeficiency > neurovirulent

50% of patients develop progressive dementia

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25
Q

How do some viruses avoid the blood-brain-barrier and enter the CNS?

A

Travel up axon fibres of peripheral nerves to CNS

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26
Q

What are some viruses that infect the CNS via peripheral nerves?

A

Rabiesvirus
Yellow fever virus
HSV 1 and 2

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27
Q

How are virions transported in the peripheral nerves?

A

Whole virions or uncoated nucleocapsids carried passively via anterograde or retrograde transport

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28
Q

Why aren’t viruses found by CD8 T cells?

A

Nerve cells express very few MHC I molecules

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29
Q

Where do viruses replicate in a neuron?

A

In cell body

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30
Q

How do virions travel from neuron to neuron?

A

Can cross synapse

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31
Q

Which viruses use blood to enter the CNS?

A

Poliovirus
Mumps virus
Measles virus
Coxsackievirus

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32
Q

How does HIV reach the CNS?

A

Via monocytes

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33
Q

What structures carry viruses into the CNS?

A 
Cerebral blood vessel
Direct spread from adjacent structures
Meningeal blood vessel
Peripheral nerve ending
Nasal mucosa
Blood vessel in choroid plexus
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34
Q

Which viruses enter through the olfactory bulb?

A

Coronavirus

HSV

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35
Q

Which viruses cause inflammatory diseases?

A

Those that directly kill neurons

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36
Q

What are the sequelae of extensive loss of neurons because of a viral infection?

A 
Mental retardation
Epilepsy
Paralysis
Deafness
Blindness
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37
Q

Which cells do viruses replicate in that cause demyelination?

A

Oligodendrocytes

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38
Q

Does the immune response also cause damage during inflammation?

A

Yes

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39
Q

Does rabiesvirus need nerve cells for its life cycle?

A

Yes

40
Q

What is the neuroinvasiveness and neurovirulence of rabiesvirus?

A

High neuroinvasiveness

High neurovirulence

41
Q

Describe the structure of rabiesvirus

A

Bullet shaped
-ve ssRNA
Helical capsid
Envelope

42
Q

Does rabiesvirus hide from the immune system when it’s in nerve cells?

A

No, rabies glycoproteins displaced on cell surface because exits cell via budding

43
Q

What kind of rabies is present in Australia?

A

Classical rabies not present

Related lyssavirus of bats

44
Q

What are the symptoms of rabies?

A

Aggression - causes animal to bite and spread virus
Thirst
Muscle spasm and terror upon attempt to drink water

45
Q

What is the pathogenesis of rabies?

A
  1. Virus entry: day 0
    - Bite of rabid animal
    - Infected saliva injected
  2. Striated muscle: day 1-60
    - Virus replicates in myocytes
  3. Peripheral nerves: day 10-60
    - Enters nerve endings
    - Nucleocapsid carried by fast axonal transport to spinal cord
  4. CNS: day 12-60
    - Travels along neurons processes > spreads > replicates
    - Neuronal dysfunction
    - Clinical rabies: day 50-70
    - Death
  5. Peripheral nerves: day 30-70
    - Travels from CNS
    - Invades salivary gland
  6. Salivary gland: day 40-70
    - Replicates in acinar cells
    - Discharged in saliva
46
Q

Can you vaccinate against rabies after infection?

A

Yes

47
Q

At what stage can you vaccinate against rabies without sequelae?

A

When in striated muscle

48
Q

At what stage can you vaccinate against rabies with minor sequelae?

A

When in peripheral nerves but not in CNS

49
Q

Which virus causes coldsores?

A

HSV 1

50
Q

Which virus causes genital warts?

A

HSV 2

51
Q

What are some viruses that belong to the herpesvirus family?

A

HSV 1 and 2

VZV

52
Q

Do herpesviruses need nerve cells for their life cycle?

A

Yes

53
Q

What is the neuroinvasiveness and neurovirulence of herpesviruses?

A

Low neuroinvasiveness

High neurovirulence

54
Q

Describe the structure of herpesviruses?

A

Linear dsDNA
Icosahedral
Envelope

55
Q

What is the normal maintenance cycle of HSV?

A

Primary infection in mucosal surfaces >
Latent infection in sensory and autonomic ganglia >
Reactivation from ganglia to mucosal surfaces

56
Q

What are the pathways leading to serious disease with HSV?

A

Viremia from primary infection > disseminated infection in organ systems > latent infection in ganglia OR deadly CNS infections
Latent infection in ganglia > deadly CNS infections

57
Q

How does HSV 1 enter the body?

A

Contact with infected saliva

Enter via cut/abrasion

58
Q

What site do primary infections of HSV 1 typically involve?

A

Mouth and/or throat

59
Q

What is the possible presentation of HSV 1 in children?

A

Gingivostamatitis

  • Ulceration in mouth
  • can spread to other areas of face in severe cases
60
Q

Is infection with HSV 1 always apparent?

A

No

61
Q

Where does skin/mucous membrane break to allow HSV entry?

A

HSV 1: mouth, throat, eyes

HSV 2: genital region

62
Q

What proportion of HSV infections cause primary disease?

A

10-15%

63
Q

What proportion of HSV infections cause inapparent infection in the lymph nodes?

A

85-90%

64
Q

What ganglia does HSV inhabit?

A

HSV 1: trigeminal

HSV 2: sacral

65
Q

What can reactivate a latent HSV infection?

A

Stress
UV
Declining immunity

66
Q

Where does HSV infect in the CNS?

A

Neurons and glia in temporal lobe

67
Q

What is the case fatality rate of HSV encephalitis?

A

70%

68
Q

What causes most cases of HSV encephalitis: reactivated or primary infections?

A

Reactivated

69
Q

How many people have a latent infection with HSV in their ganglia?

A

20%

70
Q

How is the HSV genome maintained in a latent infection?

A

As episome coated with histones

71
Q

What does the latent genome of HSV express?

A

Latency activated mRNA transcripts (LATs)

72
Q

How do CD8 T cells help maintain the HSV genome in a latent state?

A

Kill any viruses that move out of latent state

73
Q

How does VZV spread during chickenpox?

A

Haematogenously

74
Q

How does VZV enter the nerves?

A

Via vesicular rash

75
Q

How does VZV enter the body?

A

Conjuctiva and/or mucosa of URT

76
Q

Where does VZV first replicate?

A

Regional lymph nodes

77
Q

What happens during the incubation period in a VZV infection?

A

Replication in regional LNs
Primary viremia
Replication in liver and spleen
Secondary viremia

78
Q

What is the incubation time for VZV?

A

4-6 days

79
Q

When does the vesicular rash appear in VZV?

A

Day 10 after infection

80
Q

Where does VZV reside during its latent phase?

A

Dorsal root ganglia

81
Q

What causes shingles?

A

Reactivation of VZV in a dermatome

82
Q

Why is shingles more likely in older people?

A

CD8 T cells deplete with age

83
Q

Does poliovirus need nerve cells as part of its life cycle?

A

No

84
Q

What is the neuroinvasiveness and neurovirulence of poliovirus?

A

Low neuroinvasiveness

High neurovirulence

85
Q

What is the structure of poliovirus?

A

+ve ssRNA
Icosahedral
No envelope

86
Q

What is the genus of poliovirus?

A

Enterovirus

87
Q

What familydoes poliovirus belong to?

A

Picornavirus

88
Q

Is poliovirus cytocidal?

A

Yes

89
Q

What is the pathogenesis of poliovirus?

A
  1. Faecal-oral spread - ingested: day 0
  2. GALT: day 0-3
    - Tonsils and Peyer’s patches
    - Invades possibly via M cells
    - Possibly replicates in monocytes
  3. Regional LNs: day 3-5
    - Replicates
  4. Blood: day 5-15
    - Viremia
  5. BBB: day 8-12
    - Rarely
    - Crosses
  6. Spinal cord: day 10-30
    - Replicates in anterior horn cells
    - Cell destruction
    - Paralysis
  7. Gut: day 5-45
    - Normally stays here
    - Excreted in faeces
90
Q

How quickly can poliovirus cause total paralysis if it enters the CNS?

A

Hours

91
Q

How many cases of polio occur before 3?

A

50%

92
Q

How many poliovirus infections lead to irreversible paralysis?

A

Less than 1%

93
Q

Which limbs are affected more in polio?

A

Lower > acute flaccid paralysis

94
Q

What happens in the most severe cases of polio?

A

Attacks motor neurons of brainstem

  • Reduced breathing capacity
  • Increased difficulty swallowing
  • Impedes speech
95
Q

What is the route of transmission of enteroviruses?

A

Faecal-oral

96
Q

What causes enterovirus meningitis?

A

All coxsackie B types
Coxsackie A7 and A9
Many echoviruses

97
Q

When does enterovirus meningitis often occur?

A

Summer

Autumn

MD1 Neuroscience (55 decks)

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