CNS Viruses Flashcards
Neuroinvasive viruses
are capable of entering or infecting the CNS (rather than just peripheral nerves i.e. neurotropic viruses)
Neurovirulent viruses
are capable of causing disease within the CNS
Neurotropic viruses
are capable of replicating in nerve cells
Meningitis
infection of the meninges surrounding brain and spinal cord
Encephalitis
inflammation of the brain
Myelitis
infection of the spinal cord
Encephalomyelitis
inflammation of brain and spinal cord
Primary viral encephalitis (acute)
direct viral infection of the spinal cord and brain; focal or diffuse
Secondary encephalitis (post-infectious)
results from complications of a current viral infection where the virus spreads to the brain via blood
What is the most common cause of viral meningitis?
enteroviruses eg echo, coxsackie
What are less common viral causes of meningitis?
mumps, VZV, influenza, HIV< HSV2
How does the presentation of viral encephalitis differ from viral meningitis?
as viral meningitis plus personality and behavioural changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness, ultimately coma and death
What are the common causative viruses of encephalitis?
HSV1 and 2, rabiesvirus, arboviruses (insect-borne) or enteroviruses most common; mumps can cause meningitis that mildy infects brain parenchyma
What is postinfectious encephalomyelitis?
infection of the brain and spinal cord following infection such as measles, chicken pox, rubella, or mumps - no virus is actually present but there is inflammation and demyelination that is possibly autoimmune in nature (cross-reactivity bc parts of virus look like myelin sheath)
What is Guillain-Barré syndrome?
acute inflammatory demyelinating disease resulting in partial or total paralysis following infection with EBV, CMV, HIV
Reye’s syndrome
occurs post-infection with influenza or VZV in children; cerebral oedema but no inflammation; related to aspirin administration for fever
Chronic demyelinating disease
very rare e.g. subacute sclerosing panencephalitis post-measles later in life
AIDS encephalopathy/dementia complex
once HIV progresses to AIDS, it becomes neurovirulent and causes dementia
How do viruses spread to the brain?
peripheral nerves or ganglia connecting to the CNS; via blood stream (viremia)
Why are viruses ‘protected’ by axons and dendrites?
Nerve fibres do not have MHC class I molecules and therefore cytotoxic T cells cannot attack them
Which viruses can travel via peripheral axons to the CNS?
rabies, yellow fever, HSV1 & 2
Replication of viruses travelling in peripheral nerves must take place
in the body of the nerve cell as this is where protein synthesis takes place; progeny cross synaptic junctions
Retrograde viral spread occurs
from peripheral nerves to the CNS; progeny cross synaptic junctions
Anterograde viral spread occurs
from the CNS to peripheral nerves; progeny cross synaptic junctions
How do viruses spread to the brain via the blood stream?
commonly through the choroid plexus into CSF (eg mumps); cerebral vessels; meningeal vessels
Which viruses can spread to the brain via blood?
poliovirus, mumps, measles, coxsackie, HIV in monocytes
Viruses affecting the nasopharynx can travel to the brain via
the olfactory bulb (coronavirus, HSV, H5N1)
How do viruses cause damage in the brain?
directly killing neurons (causes inflammatory response as tight junctions open up and allow lymphocytes, antibodies, immune effectors usually blocked by BBB); or replicate in non-neuronal cells (eg oligodendrocytes) triggering demyelination
What is obligatory in the life cycle of rabiesvirus?
growth in nerve cells
Rabiesvirus has (neuroinvasiveness, neurovirulence)
high neuroinvasiveness, high neurovirulence
What is the structure of rabiesvirus?
bullet shaped -ve RNA virus w/helical capsid and envelope (tf must bud from cells to get its envelope glycoproteins - these are a target for antibodies)
What is the nature of damage in rabiesvirus?
because it has an envelope it must bud from the cell to get its glycoproteins which are expressed on the cell - these are targets for antibodies to kill the cells
What is the pathogenesis of rabiesvirus?
infected animal bite breaks skin; virus replicates in myocytes (1-60); virus enters peripheral nerve endings and carried to spinal cord (10-60); travels in CNS, causes neuronal dysfunction (12-60); clinical rabies, death (50-70); travels from CNS to salivary glands (30-70); replicates in salivary acinar cells (40-70)
What are the symptoms of rabiesvirus?
aggression (hence biting), thirst but muscle spasm and fear of drinking water
What is obligatory in the life cycle of alpha herpesviruses (HSV1 & 2, VZV)?
growth in nerve cells
Alpha HSV viruses (neuroinvasiveness, neurovirulence)
low neuroinvasiveness, high neurovirulence
What is the structure of alpha herpesviruses?
linear dsDNA, icosahedral, surrounded by envelope
What is the pathogenesis of HSV?
infected saliva enters break in skin or mucous membranes (HSV1: mouth, throat, eye; HSV2: genitals) and multiplies locally; in 90% of cases it goes on to multiply in regional lymph nodes as an inapparent infection and resolve; 10-15% develop primary disease that enters adjacent nerve endings (occurs directly in 5%) where it then migrates along axons to sensory nerve ganglia where it resides as a latent infection until immunity is compromised and it is reactivated; on reactivation get localized multiplication and disease reoccurrence; *= rarely it enters the blood and travels to organs causing severe sporadic encephalitis of the temporal lobe
What happens in the latent phase of HSV infection?
20% of people harbour genome episome (closed circular dsDNA) covered in histones w/latency activated mRNA transcripts (LATs); it is maintained in the latent phase by CD8 T cells killing infected cells (this is why you get reoccurrence in old age/when the immunity wanes)
What is the pathogenesis of VZV?
infection of conjunctiva and/or URT; replicates in regional lymph nodes; primary viraemia in bloodstream (4-6); further replication in liver and spleen; secondary viraemia; infection of skin + vesicular rash (10); scratching aeresolizes virus and cycle repeats; in 10-20% of cases, from the RASH the virus can go up to dorsal root ganglia and become latent
What is different about the life cycle of poliovirus vs the alpha herpesviruses and rabiesvirus?
growth in nerve cells is NOT an obligatory part of the life cycle
Poliovirus (neuroinvasiveness, neurovirulence)
low neuroinvasiveness, high neurovirulence
What is the structure of poliovirus?
+ve RNA, icosahedral capsid, no envelope - kills cells in which it replicates
What is the pathogenesis of poliovirus?
ingested from faecally contaminated food or water; replicates in tonsils, then Peyer’s patches of GIT (0-3) - excreted in faeces (5-45, normal); replicates in regional lymph nodes (3-5); enters blood (5-15) and crosses BBB (8-12) to anterior horn cells of spinal cord (10-30), destroying them and causing paralysis (12-30)
What is the pathogenesis of enteroviruses (coxsackie A & B, echoviruses, poliovirus)?
faecal-oral route; primary and secondary viraemia via lymphoid tissues into the blood
