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
What is myelitis?
Inflammation of the spinal cord
What is encephalomyelitis?
Inflammation of both the brain and spinal cord
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
Describe the general presentation of viral meningits?
What is the major cause of viral meningitis?
Describe the causes of viral meningitis, other than enteroviruses?
Herpes simplex 2 (genital)
Describe the presentation of viral encephalitis?
Like meningitis, but followed by:
Personality and behavioural changes
Altered levels of consciousness
Coma and death
What is the major cause of viral encephalitis?
Herpes simplex virus types 1 and 2
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)
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
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
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
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
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
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
Where does viral replication take place in the nervous system? Why?
In the body, as this is where protein synthesis takes place
How can the viruses access the CNS, other than via the PNS?
Can occur via cerebral blood vessels, choroid plexus or memingeal blood vessels
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
Describe the effect of inflammation on the blood brain barrier?
During inflamamtion, lymphocytes, antibodies and other immune effectors can enter (they are normally excluded)
Describe the neuroinvasiveness and neurovirulence of rabiesvirus?
High neuroinvasiveness and high neurovirulence
Does rabiesvirus require growth in nerve cells as part of its life cycle?
Describe the morphology of the rabiesvirus?
-ve stranded RNA
How does rabiesvirus exit nerve cells?
Describe the pathogenesis of rabies?
Describe the symptoms of rabies?
Thirst, but muscle spasm and terror upon attempt to drink water
Describe the time frame for infection with rabiesvirus?
Symptoms anywhere between 40 and 70 days after infection
Which is the only disease for which vaccination is helpful after infection?
60 day window of opportunity to catch virus before it gets to brain and mount immune response
Which viruses are alpha herpesviruses?
HSV 1 and 2
Do the alpha herpesviruses require growth in nerve cells as part of their life cycle?
Describe the neuroinvasiveness and neurovirulence of alpha herpesviruses?
Describe the morphology of alpha herpesviruses?
Linear dsDNA genome
How do alpha herpesvirsues enter the body?
Via mucosal surfaces
When does serious disease occur with alpha herpesviruses?
If virus moves from mucosal surface to blood and replicates (then enters brain and spinal cord)
Where do latent infections of alpha herpesviruses reside?
Sensory and autonomic ganglia
How is HSV1 transmitted?
Contact with infected saliva
Which body parts are usually implicated in primary infections with HSV1?
Mouth and/or throat
May be inapparent
Gingivomastitis in children
Describe the pathogensis of HSV?
What is the most dangeorus outocome of HSV infection?
Severe sporadic encephalitis
Infects neurons and glia in temporal lobe
What is the most common cause of severe sporadic encephalitis?
Usually reactivation of latent infection, not a primary infection
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)
What does HSV express in its latent state?
Latency activated mRNA transcripts (LATs)
How is varicella-zoster virus spread within the body?
During chickenpox - haematogenous spread
Susequently enters nerves to cause vesicular rashes
Describe the pathogenesis of chickenpox?
How can varicella-zoster virus become latent?
From the rash, can travel back up to DRG and become latent
What is shingles?
Reactivation of latent varicella-zoster virus
Painful blisters that follow a dermatome
In which population does shingles most commonly occur?
When CTL response starts to wane, and infection cannot be kept latent
What type of virus is poliovirus?
How is poliovirus spread?
Does poliovirus require growth in nerve cells as part of its life cycle?
Occurs as an accident
Describe the neuroinvasiveness and neurovirulence of poliovirus?
Describe the morphology of poliovirus?
Describe the effect that poliovirus has on the cells that it infects?
Cytocidal virus > kills cells in which it replicates
How does poliovirus exit cells?
Kills cell that it is in so that it is released
Describe the pathogenesis of poliovirus?
Which cell types does poliovirus target? Why?
Anterior horn cells in spinal cord
These cells have receptor that virus can use to replicate
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
When do epidemics of enterovirus meningitis occur?