CNS Viruses

Question 1

Neuroinvasive viruses

Answer 1

are capable of entering or infecting the CNS (rather than just peripheral nerves i.e. neurotropic viruses)

Question 2

Neurovirulent viruses

Answer 2

are capable of causing disease within the CNS

Question 3

Neurotropic viruses

Answer 3

are capable of replicating in nerve cells

Question 4

Meningitis

Answer 4

infection of the meninges surrounding brain and spinal cord

Question 5

Encephalitis

Answer 5

inflammation of the brain

Question 6

Myelitis

Answer 6

infection of the spinal cord

Question 7

Encephalomyelitis

Answer 7

inflammation of brain and spinal cord

Question 8

Primary viral encephalitis (acute)

Answer 8

direct viral infection of the spinal cord and brain; focal or diffuse

Question 9

Secondary encephalitis (post-infectious)

Answer 9

results from complications of a current viral infection where the virus spreads to the brain via blood

Question 10

What is the most common cause of viral meningitis?

Answer 10

enteroviruses eg echo, coxsackie

Question 11

What are less common viral causes of meningitis?

Answer 11

mumps, VZV, influenza, HIV< HSV2

Question 12

How does the presentation of viral encephalitis differ from viral meningitis?

Answer 12

as viral meningitis plus personality and behavioural changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness, ultimately coma and death

Question 13

What are the common causative viruses of encephalitis?

Answer 13

HSV1 and 2, rabiesvirus, arboviruses (insect-borne) or enteroviruses most common; mumps can cause meningitis that mildy infects brain parenchyma

Question 14

What is postinfectious encephalomyelitis?

Answer 14

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)

Question 15

What is Guillain-Barré syndrome?

Answer 15

acute inflammatory demyelinating disease resulting in partial or total paralysis following infection with EBV, CMV, HIV

Question 16

Reye’s syndrome

Answer 16

occurs post-infection with influenza or VZV in children; cerebral oedema but no inflammation; related to aspirin administration for fever

Question 17

Chronic demyelinating disease

Answer 17

very rare e.g. subacute sclerosing panencephalitis post-measles later in life

Question 18

AIDS encephalopathy/dementia complex

Answer 18

once HIV progresses to AIDS, it becomes neurovirulent and causes dementia

Question 19

How do viruses spread to the brain?

Answer 19

peripheral nerves or ganglia connecting to the CNS; via blood stream (viremia)

Question 20

Why are viruses ‘protected’ by axons and dendrites?

Answer 20

Nerve fibres do not have MHC class I molecules and therefore cytotoxic T cells cannot attack them

Question 21

Which viruses can travel via peripheral axons to the CNS?

Answer 21

rabies, yellow fever, HSV1 & 2

Question 22

Replication of viruses travelling in peripheral nerves must take place

Answer 22

in the body of the nerve cell as this is where protein synthesis takes place; progeny cross synaptic junctions

Question 23

Retrograde viral spread occurs

Answer 23

from peripheral nerves to the CNS; progeny cross synaptic junctions

Question 24

Anterograde viral spread occurs

Answer 24

from the CNS to peripheral nerves; progeny cross synaptic junctions

Question 25

How do viruses spread to the brain via the blood stream?

Answer 25

commonly through the choroid plexus into CSF (eg mumps); cerebral vessels; meningeal vessels

Question 26

Which viruses can spread to the brain via blood?

Answer 26

poliovirus, mumps, measles, coxsackie, HIV in monocytes

Question 27

Viruses affecting the nasopharynx can travel to the brain via

Answer 27

the olfactory bulb (coronavirus, HSV, H5N1)

Question 28

How do viruses cause damage in the brain?

Answer 28

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

Question 29

What is obligatory in the life cycle of rabiesvirus?

Answer 29

growth in nerve cells

Question 30

Rabiesvirus has (neuroinvasiveness, neurovirulence)

Answer 30

high neuroinvasiveness, high neurovirulence

Question 31

What is the structure of rabiesvirus?

Answer 31

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)

Question 32

What is the nature of damage in rabiesvirus?

Answer 32

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

Question 33

What is the pathogenesis of rabiesvirus?

Answer 33

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)

Question 34

What are the symptoms of rabiesvirus?

Answer 34

aggression (hence biting), thirst but muscle spasm and fear of drinking water

Question 35

What is obligatory in the life cycle of alpha herpesviruses (HSV1 & 2, VZV)?

Answer 35

growth in nerve cells

Question 36

Alpha HSV viruses (neuroinvasiveness, neurovirulence)

Answer 36

low neuroinvasiveness, high neurovirulence

Question 37

What is the structure of alpha herpesviruses?

Answer 37

linear dsDNA, icosahedral, surrounded by envelope

Question 38

What is the pathogenesis of HSV?

Answer 38

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

Question 39

What happens in the latent phase of HSV infection?

Answer 39

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)

Question 40

What is the pathogenesis of VZV?

Answer 40

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

Question 41

What is different about the life cycle of poliovirus vs the alpha herpesviruses and rabiesvirus?

Answer 41

growth in nerve cells is NOT an obligatory part of the life cycle

Question 42

Poliovirus (neuroinvasiveness, neurovirulence)

Answer 42

low neuroinvasiveness, high neurovirulence

Question 43

What is the structure of poliovirus?

Answer 43

+ve RNA, icosahedral capsid, no envelope - kills cells in which it replicates

Question 44

What is the pathogenesis of poliovirus?

Answer 44

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)

Question 45

What is the pathogenesis of enteroviruses (coxsackie A & B, echoviruses, poliovirus)?

Answer 45

faecal-oral route; primary and secondary viraemia via lymphoid tissues into the blood