Flashcards in Viruses Affecting the Central Nervous System Deck (97):
What is a neurotropic virus?
Capable of replicating in nerve cells
What is a neuroinvasive virus?
Capable of entering/infecting CNS
What is a neurovirulent virus?
Capable of causing disease within nervous system
What is encephalomyelitis?
Inflammation of brain and spinal cord
What is primary viral encephalitis/acute viral encephalitis?
Direct viral infection of spinal cord and brain
Can be focal or diffuse
What is secondary encephalitis/post-infectious encephalitis?
From complications of current viral infection
Virus spreads to brain
What is the most common route viruses take to the brain?
What is more common: viral or bacterial meningitis?
What is more severe: viral or bacterial meningitis?
What is the presentation of meningitis?
What is the main viral cause of meningitis?
How do enteroviruses enter the body?
What are some other viral causes of meningitis, that aren't enteroviruses?
What is more severe: viral or bacterial encephalitis?
What is the presentation of encephalitis?
Like meningitis, but also
- Personality and behavioural changes
- Partial paralysis
- Altered state of consciousness
- Ultimately coma and death
What are the most common causes of viral encephalitis?
HSV 1 and 2
Can mumps virus meningitis also cause encephalitis?
Yes but is generally mild
What is post-infectious encephalomyelitis?
Occurs few days after infections
No virus present but
Possibly autoimmune in nature
Which viruses can cause post-infectious encephalomyelitis?
What is Guillain-Barre syndrome?
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
Which viruses can cause Guillain-Barre syndrome?
What is Reye's syndrome?
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
What are chronic demyelinating diseases?
Eg: sub-acute sclerosing panencephalitis (SSPE)
- Late sequel (30 yrs) to measles infection
What is AIDS encephalopathy/AIDS dementia complex?
HIV infection > immunodeficiency > neurovirulent
50% of patients develop progressive dementia
How do some viruses avoid the blood-brain-barrier and enter the CNS?
Travel up axon fibres of peripheral nerves to CNS
What are some viruses that infect the CNS via peripheral nerves?
Yellow fever virus
HSV 1 and 2
How are virions transported in the peripheral nerves?
Whole virions or uncoated nucleocapsids carried passively via anterograde or retrograde transport
Why aren't viruses found by CD8 T cells?
Nerve cells express very few MHC I molecules
Where do viruses replicate in a neuron?
In cell body
How do virions travel from neuron to neuron?
Can cross synapse
Which viruses use blood to enter the CNS?
How does HIV reach the CNS?
What structures carry viruses into the CNS?
Cerebral blood vessel
Direct spread from adjacent structures
Meningeal blood vessel
Peripheral nerve ending
Blood vessel in choroid plexus
Which viruses enter through the olfactory bulb?
Which viruses cause inflammatory diseases?
Those that directly kill neurons
What are the sequelae of extensive loss of neurons because of a viral infection?
Which cells do viruses replicate in that cause demyelination?
Does the immune response also cause damage during inflammation?
Does rabiesvirus need nerve cells for its life cycle?
What is the neuroinvasiveness and neurovirulence of rabiesvirus?
Describe the structure of rabiesvirus
Does rabiesvirus hide from the immune system when it's in nerve cells?
No, rabies glycoproteins displaced on cell surface because exits cell via budding
What kind of rabies is present in Australia?
Classical rabies not present
Related lyssavirus of bats
What are the symptoms of rabies?
Aggression - causes animal to bite and spread virus
Muscle spasm and terror upon attempt to drink water
What is the pathogenesis of rabies?
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
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
Can you vaccinate against rabies after infection?
At what stage can you vaccinate against rabies without sequelae?
When in striated muscle
At what stage can you vaccinate against rabies with minor sequelae?
When in peripheral nerves but not in CNS
Which virus causes coldsores?
Which virus causes genital warts?
What are some viruses that belong to the herpesvirus family?
HSV 1 and 2
Do herpesviruses need nerve cells for their life cycle?
What is the neuroinvasiveness and neurovirulence of herpesviruses?
Describe the structure of herpesviruses?
What is the normal maintenance cycle of HSV?
Primary infection in mucosal surfaces >
Latent infection in sensory and autonomic ganglia >
Reactivation from ganglia to mucosal surfaces
What are the pathways leading to serious disease with HSV?
Viremia from primary infection > disseminated infection in organ systems > latent infection in ganglia OR deadly CNS infections
Latent infection in ganglia > deadly CNS infections
How does HSV 1 enter the body?
Contact with infected saliva
Enter via cut/abrasion
What site do primary infections of HSV 1 typically involve?
Mouth and/or throat
What is the possible presentation of HSV 1 in children?
- Ulceration in mouth
- can spread to other areas of face in severe cases
Is infection with HSV 1 always apparent?
Where does skin/mucous membrane break to allow HSV entry?
HSV 1: mouth, throat, eyes
HSV 2: genital region
What proportion of HSV infections cause primary disease?
What proportion of HSV infections cause inapparent infection in the lymph nodes?
What ganglia does HSV inhabit?
HSV 1: trigeminal
HSV 2: sacral
What can reactivate a latent HSV infection?
Where does HSV infect in the CNS?
Neurons and glia in temporal lobe
What is the case fatality rate of HSV encephalitis?
What causes most cases of HSV encephalitis: reactivated or primary infections?
How many people have a latent infection with HSV in their ganglia?
How is the HSV genome maintained in a latent infection?
As episome coated with histones
What does the latent genome of HSV express?
Latency activated mRNA transcripts (LATs)
How do CD8 T cells help maintain the HSV genome in a latent state?
Kill any viruses that move out of latent state
How does VZV spread during chickenpox?
How does VZV enter the nerves?
Via vesicular rash
How does VZV enter the body?
Conjuctiva and/or mucosa of URT
Where does VZV first replicate?
Regional lymph nodes
What happens during the incubation period in a VZV infection?
Replication in regional LNs
Replication in liver and spleen
What is the incubation time for VZV?
When does the vesicular rash appear in VZV?
Day 10 after infection
Where does VZV reside during its latent phase?
Dorsal root ganglia
What causes shingles?
Reactivation of VZV in a dermatome
Why is shingles more likely in older people?
CD8 T cells deplete with age
Does poliovirus need nerve cells as part of its life cycle?
What is the neuroinvasiveness and neurovirulence of poliovirus?
What is the structure of poliovirus?
What is the genus of poliovirus?
What familydoes poliovirus belong to?
Is poliovirus cytocidal?
What is the pathogenesis of poliovirus?
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
4. Blood: day 5-15
5. BBB: day 8-12
6. Spinal cord: day 10-30
- Replicates in anterior horn cells
- Cell destruction
7. Gut: day 5-45
- Normally stays here
- Excreted in faeces
How quickly can poliovirus cause total paralysis if it enters the CNS?
How many cases of polio occur before 3?
How many poliovirus infections lead to irreversible paralysis?
Less than 1%
Which limbs are affected more in polio?
Lower > acute flaccid paralysis
What happens in the most severe cases of polio?
Attacks motor neurons of brainstem
- Reduced breathing capacity
- Increased difficulty swallowing
- Impedes speech
What is the route of transmission of enteroviruses?
What causes enterovirus meningitis?
All coxsackie B types
Coxsackie A7 and A9