37 - Viruses Affecting the CNS Flashcards
Neurotropic
Can replicate in neurons
Neuroinvasive
Capable of entering or infecting the CNS
Neurovirulent
Capable of causing disease of the CNS
Primary viral encephalitis
Direct viral infection of the spinal cord and brain. Can be focal or diffuse.
Secondary viral encephalitis
From complications of a current viral infection where virus spreads to the brain, usually via the blood.
Viral causes of encephalitis
- 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
Viral causes of meningitis
• 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).
Presentation of viral encephalitis
Presentation initially like meningitis, then personality and behavioral changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness, ultimately coma and death.
Post-infectious encephalomyelitis
1
2
3
• 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
Guillain-Barre syndrome
1
2
- 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
Reye's syndrome 1 2 3 4
- 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
Chronic demyelinating viral disease
- Very rare
* Exemplified by sub-acute sclerosing panencephalitis (SSPE), a late sequel to measles infection
AIDS encephalopathy
1
2
- Once HIV infection leads to immunodeficiency the neurovirulence of HIV manifests
- 50% of patients develop progressive dementia
Ways for viruses to invade CNS
1
2
3
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)
How do virions travel anterograde in axons?
Using kinesin protein
How do virions travel retrograde in axons?
Using dynein protein
How do viruses replicating in neurons evade CTL attack>
Neurons lack MHC I
Where in a neuron can viruses replicate?
Only in nerve body (here protein synthesis occurs)
Blood vessel often used by mumps to enter CNS
Blood vessels through choroid plexus
Ways in which viruses can cause damage in the brain
1
2
3
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
Rabiesvirus morphology
-ve stranded RNA.
Helical capsid.
Envelope
Is rabiesvirus very good at evading the immune system?
No.
Replication in infected neurons leads to display of rabies envelope glycoproteins on cell membranes.
Rabiesvirus transmission
Present in infectious saliva.
Need to bite thorough skin to transmit.
Time between becoming infected with rabies and becoming infectious (from saliva)
40 - 70 days
Basic rabies life-cycle 1 2 3 4 5 6
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)
Alpha herpesvirus morphology
Linear dsDNA genome
Icosahedral, enveloped virion.
EG HSV, VZV
Example of a severe peripheral HSV presentation
Gingivostomatitis
Example of a severe central HSV presentation
Severe sporadic encephalitis.
HSV enters CNS, infects glia, neurons.
~70% case fatality rate.
Mostly from reactivated, not primary infections
Proportion of people who harbour HSV episome
~20%
Transcription products from latent HSV episomes
Latency-activated transcripts (~2kb).
mRNA transcripts
VZV basic pathogenesis 1 2 3 4 5 6 7
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
Is neuroinvasion an obligatory part of poliovirus life-cycle?
No
Poliovirus morphology
+ sense
ssRNA
Icosahedral capsid, no envelope.
Picornaviridae
If poliovirus enters CNS, where does it replicate?
Anterior horn cells (motor)
Limbs most often affected by polio myelitis
Lower limbs, leading to flaccid paralysis
How rapidly can polio cause paralysis?
Within hours of entering CNS
Proportion of polio infections that lead to irreversible paralysis
~1%
Most severe polio cases
Polio destroys motor neurons of brainstem, reduces breathing capacity, increases difficulty swallowing, impedes speech articulation
Mortality rate of poliomyelitis
5-10%
Coxsackie A and B
1 - 7
• 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
