Viruses affecting the Central Nervous System Flashcards
What does neurotropic mean?
Capable of replicating in nerve cells
What does neuroinvasive mean?
Capable of entering or infecting the central nervous system
What does neurovirulent mean?
Capable of causing disease within the nervous system
What is meningitis?
Infection of the meninges, the membranes that surround the brain and spinal cord
What is encephalitis?
Inflammation of the brain itself
What is myelitis?
An infection of the spinal cord.
What is encephalomyelitis?
When both the brain and the spinal cord become inflamed
What is primary viral encephalitis (also called acute viral encephalitis)?
Direct viral infection of the spinal cord and brain.
Can be focal or diffuse.
What is secondary encephalitis (aka post-infectious encephalitis)?
The result of complications from a current viral infection where virus spreads to the brain, usually via the blood
What is more common, viral or bacterial meningitis?
Viral is more common but less severe
How does viral meningitis present?
Headache
Fever
Neck stiffness
With or without vomiting and/or photophobia
What are the common causes of viral meningitis?
Enteroviruses (common viruses that enter the body through the mouth)
What are less common causes of viral meningitis?
Mumps
Varicella zoster
Influenza
HIV
Herpes simplex type 2 (genital herpes)
What is one of the most serious viral diseases?
Viral encephilitis
How does viral encephalitis present?
Like meningitis
But also personality and behavioural changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness
Ultimately coma and death.
What are the common causes of viral encephalitis?
Herpes simplex virus types 1 and 2
Rabiesvirus
Arboviruses (insect-borne viruses)
Enteroviruses
When does post-infectious encephalomyelitis occur?
A few days after infections such as measles, chickenpox, rubella or mumps
What is present in postinfectious encephalomyelitis?
No virus present but inflammation and demyelination are evident
What is Guillain-Barre syndrome?
Which viruses can cause this?
Acute inflammatory demyelinating disease
EBV, CMV, HIV
What does Guillain-Barre syndrome result in?
Partial or complete paralysis
Most people (75%) fully recover within weeks
Does Guillain-Barre require active infection for an outbreak to occur?
No
What is Reye’s syndrome?
A post-infection from influenza or chickenpox in children leading to cerebral oedema.
What happens to the brain in Reye’s syndrome?
Cerebral edema but no inflammation
What is Reye’s syndrome epidemiologically associated with?
Administration of aspirin during initial fever
What are chronic demyelinating diseases exemplified by?
Sub-acute sclerosing panencephalitis (SSPE), a late sequel to measles infection
How do viruses spread to the brain?
Viruses exploit the connection of the peripheral nervous system to the CNS by travelling up the axon, as whole virions or uncoated nucleocapsids are carried passively along axons or dendrites in the peripheral nervous system.
How are viruses protected from attack by nerve cells?
Neurons lack MHC Class I molecules, therefore viruses are protected from attack by CTL.
Where in the nerve does viral replication take place?
In the body of nerve as this is where protein synthesis takes place
Can the released viral progeny cross the synaptic junction?
Yes
How does retrograde viral spread occur?
Uptake at axon
Transport up axon
Replication in soma
Transsynaptic spread
Transport up axon
Replication
How does anterograde viral spread occur?
Uprake and replication in soma
Transport down axon
Transsynaptic spread
Tansport down axon
Can other viruses enter the CNS directly via the blood stream like in other tissues?
Yes
E.g. poliovirus, mumps virus, measles virus, coxsackievirus; also HIV in monocytes
Can viruses enter via the olfactory bulb?
Yes
Coronavirus, herpes simplex virus
What are the two possible effects viruses can have once in the brain?
- Killing neurons directly (inflammatory disease) leading to mental retardation, epilepsy, paralysis, deafness or blindness.
- Replication in non-neuronal cells (e.g. oligodendrocytes) causing demyelination.
What happens to the blood-brain barrier during inflammation?
Lymphocytes, antibodies and other immune effectors can enter
What is an obligatory part of the rabiesvirus life cycle?
Growth in nerve cells
Why can rabiesvirus enter the CNS?
High neuroinvasiveness and high neurovirulence
What are the physical characteristics of rabiesvirus?
Bullet-shaped
–ve stranded RNA virus
Helical capsid and an envelope
Does rabiesvirus hide from the immune system in nerve cells?
No
What does rabiesvirus replication in the nerve cell body lead to?
Rabies glycoprotein displayed on the cell surface
What are the signs and symptoms of rabiesvirus infection?
Aggression
Thirst but muscle spasm and terror upon attempt to drink water
What is the pathogenic mechanism of rabiesvirus?
Replicates in myocytes locally
Reaches motor nerve
Travels up peripheral nerve to spinal cord then brain
Infects brain
Migrates down from brain into salivary glands
Poured out into saliva
What comprises the alpha herpesviruses?
Herpes simplex viruses 1 and 2 (HSV)
Varicella-zoster virus (VSV)
What is an obligatory part of the alpha herpesvirus life cycle?
Growth in nerve cells
What is the neuroinvasiveness and neurovirulence of alpha herpesviruses?
Low neuroinvasiveness
High neurovirulence
What is the genetic structure of alpha herpesviruses?
Linear dsDNA genome
What is the physical structure of alpha herpesviruses?
Icosahedral and surrounded by an envelope
What is the normal maintenance cycle of alpha herpesviruses?
Infects mucosal surfaces and then enters latent infection in sensory and autonomic ganglia.
Possibility for viraemia.
What is the pathway leading to serious disease from alpha herpesviruses?
Primary infection leads to viraemia and disseminated infection that can infect CNS.
Infection in sensory/autonomic ganglia leads to CNS infection.
How does HSV 1 enter the body?
Through contact with infected saliva.
Which region of the body do primary herpes simplex type 1 viruses typically involve?
The mouth and/or throat
What is the pathogenesis of herpes simplex virus type 1?
See image
What percentage of people harbour the latent herpes simplex 1 virus in their ganglia?
20%
How is herpes simplex 1 genome maintained during latency?
As an episome coated with histones
Is there any structural gene expression during latency of HSV1?
No
What is expressed during HSV1 latency?
2kb latency activated mRNA transcripts (LATs)
What is varicella-zoster virus the cause of?
Chicken pox (varicella)
Shingles (zoster)
How does VZV spread during chickenpox?
Hematogenous (by the blood)
Virus subsequently enters the nerves from the resulting vesicular rash.
What happens during chickenpox?
See image
What happens during the reactivation phase of VZV that results in shingles?
Recurrent infection of VZV causes painful blisters of shingles that follow a dermatome.
Is growth of poliovirus in nerve cells an obligatory part of the life cycle?
No
What is the neuroinvasiveness and neurovirulence of poliovirus?
Low neuroinvasiveness
High neurovirulence
What is the physical structure of poliovirus?
+ve stranded RNA virus
Icosahedral capsid and no envelope
What effect does poliovirus have on the cells it’s in?
Kills them (cytocidal virus)
Which family does poliovirus belong to?
Picornavirus
What is the pathogenesis of poliovirus?
Poliovirus travels in the blood as free virus and can target the motor neuron cells in the anterior horn leading to paralysis (see image).
What may poliovirus cause within hours if it invades the CNS?
Paralysis
Which neurons does poliovirus kill?
Motoneurons
True or false: the majority of poliovirus infections lead to irreversible paralysis.
False
Less than 1% of infections lead to irreversible paralysis
Which limbs are more affected in poliovirus infections?
Lower limbs are affected more often than the upper limbs, leading to acute flaccid paralysis.
Which enteroviruses lead to meningitis?
All coxsackie B types, coxsackie A7 and A9 many echoviruses
What is the pathogenesis of enteroviruses?
Primary viraemia in circulation leads to secondary viraemia in target tissues, such as brain, meninges, liver, skin and muscle (see image).
