37 - Viruses Affecting the CNS

Question 1

Neurotropic

Answer 1

Can replicate in neurons

Question 2

Neuroinvasive

Answer 2

Capable of entering or infecting the CNS

Question 3

Neurovirulent

Answer 3

Capable of causing disease of the CNS

Question 4

Primary viral encephalitis

Answer 4

Direct viral infection of the spinal cord and brain. Can be focal or diffuse.

Question 5

Secondary viral encephalitis

Answer 5

From complications of a current viral infection where virus spreads to the brain, usually via the blood.

Question 6

Viral causes of encephalitis

Answer 6

• Mostly caused by herpes simplex virus types 1 and 2, rabiesvirus, arboviruses (insect-borne viruses) or enteroviruses
• Mumps virus meningitis can also involve the brain parenchyma but is generally mild

Question 7

Viral causes of meningitis

Answer 7

• Main cause is enteroviruses (common viruses that enter the body through the
mouth)
• Other viral causes - mumps, varicella zoster, influenza, HIV, and herpes
simplex type 2 (genital herpes).

Question 8

Presentation of viral encephalitis

Answer 8

Presentation initially like meningitis, then personality and behavioral changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness, ultimately coma and death.

Question 9

Post-infectious encephalomyelitis
1
2
3

Answer 9

• Can occur a few days after infections such as measles, chickenpox, rubella or
mumps
• No virus present but inflammation and demyelination are evident
• Possibly autoimmune in nature

Question 10

Guillain-Barre syndrome
1
2

Answer 10

• Is an acute inflammatory demyelinating disease following infection with several viruses such as EBV, CMV, HIV
• Results in partial or total paralysis but most people (75%) fully recover within weeks

Question 11

Reye's syndrome 
1
2
3
4

Answer 11

• Post-infection with influenza or chickenpox in children
• 25% case-fatality rate
• Cerebral edema but not inflammation
• Epidemiological association with administration of aspirin during initial fever

Question 12

Chronic demyelinating viral disease

Answer 12

• Very rare

* Exemplified by sub-acute sclerosing panencephalitis (SSPE), a late sequel to measles infection

Question 13

AIDS encephalopathy
1
2

Answer 13

• Once HIV infection leads to immunodeficiency the neurovirulence of HIV manifests
• 50% of patients develop progressive dementia

Question 14

Ways for viruses to invade CNS
1
2
3

Answer 14

1) In the blood (must be able to pass blood brain barrier) (EG polio, mumps, measles, coxsackievirus, HIV in monocytes)
2) Through peripheral nerves into CNS (EG rabies, yellow fever, HSV 1 and 2)
3) Via olfactory bulb (EG coronavirus, HSV)

Question 15

How do virions travel anterograde in axons?

Answer 15

Using kinesin protein

Question 16

How do virions travel retrograde in axons?

Answer 16

Using dynein protein

Question 17

How do viruses replicating in neurons evade CTL attack>

Answer 17

Neurons lack MHC I

Question 18

Where in a neuron can viruses replicate?

Answer 18

Only in nerve body (here protein synthesis occurs)

Question 19

Blood vessel often used by mumps to enter CNS

Answer 19

Blood vessels through choroid plexus

Question 20

Ways in which viruses can cause damage in the brain
1
2
3

Answer 20

1) Kill neurons
2) Kill glial cells (EG oligodendrocytes, leading to demyelination)
3) BBB normally prevents lymphocytes, etc, form entering brain, but during inflammation these can enter, causing damage

Question 21

Rabiesvirus morphology

Answer 21

-ve stranded RNA.
Helical capsid.
Envelope

Question 22

Is rabiesvirus very good at evading the immune system?

Answer 22

No.

Replication in infected neurons leads to display of rabies envelope glycoproteins on cell membranes.

Question 23

Rabiesvirus transmission

Answer 23

Present in infectious saliva.

Need to bite thorough skin to transmit.

Question 24

Time between becoming infected with rabies and becoming infectious (from saliva)

Answer 24

40 - 70 days

Question 25

Basic rabies life-cycle
1
2
3
4
5
6

Answer 25

1) Enters host (day 0)
2) Replicate in striated muscle (day 1 - 60)
3) Enter peripheral nerves (day 10 - 60). Moves ~8-20mm per day)
4) Enters CNS (day 12 - 60), leading to clinical rabies (day 50 - 70)
5) Travel from CNS to salivary glands via peripheral nerves (day 30 - 70)
6) Replication in salivary glands (day 40 - 70)

Question 26

Alpha herpesvirus morphology

Answer 26

Linear dsDNA genome
Icosahedral, enveloped virion.
EG HSV, VZV

Question 27

Example of a severe peripheral HSV presentation

Answer 27

Gingivostomatitis

Question 28

Example of a severe central HSV presentation

Answer 28

Severe sporadic encephalitis.
HSV enters CNS, infects glia, neurons.
~70% case fatality rate.
Mostly from reactivated, not primary infections

Question 29

Proportion of people who harbour HSV episome

Answer 29

~20%

Question 30

Transcription products from latent HSV episomes

Answer 30

Latency-activated transcripts (~2kb).

mRNA transcripts

Question 31

VZV basic pathogenesis
1
2
3
4
5
6
7

Answer 31

1) Infection of conjunctiva or URT mucosa
2) Replication in regional lymph nodes
3) Primary viremia in bloodstream
4) Further replication in liver and spleen
5) Secondary viremia
6) Infection of skin and appearance of vesicular rash
7) From rash, can ascend sensory nerve to dorsal root ganglia, become latent

Question 32

Is neuroinvasion an obligatory part of poliovirus life-cycle?

Answer 32

No

Question 33

Poliovirus morphology

Answer 33

+ sense
ssRNA
Icosahedral capsid, no envelope.
Picornaviridae

Question 34

If poliovirus enters CNS, where does it replicate?

Answer 34

Anterior horn cells (motor)

Question 35

Limbs most often affected by polio myelitis

Answer 35

Lower limbs, leading to flaccid paralysis

Question 36

How rapidly can polio cause paralysis?

Answer 36

Within hours of entering CNS

Question 37

Proportion of polio infections that lead to irreversible paralysis

Answer 37

~1%

Question 38

Most severe polio cases

Answer 38

Polio destroys motor neurons of brainstem, reduces breathing capacity, increases difficulty swallowing, impedes speech articulation

Question 39

Mortality rate of poliomyelitis

Answer 39

5-10%

Question 40

Coxsackie A and B

1 - 7

Answer 40

• Picornaviridae
• Spread by fecal-oral route
• Circulate in blood to target
organs
Can cause Enterovirus meningitis:
• All coxsackie B types, coxsackie A7 and A9 many
echoviruses
• Often occurs during a summer/autumn epidemic
• Can be the sole presentation while other individuals may
have rashes, myositis