Viruses Affecting the Central Nervous System Flashcards by Srishti D

What is a neurotropic virus?

Capable of replicating in nerve cells

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What is a neuroinvasive virus?

Capable of entering/infecting CNS

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What is a neurovirulent virus?

Capable of causing disease within nervous system

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What is encephalomyelitis?

Inflammation of brain and spinal cord

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What is primary viral encephalitis/acute viral encephalitis?

Direct viral infection of spinal cord and brain

Can be focal or diffuse

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What is secondary encephalitis/post-infectious encephalitis?

From complications of current viral infection

Virus spreads to brain

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What is the most common route viruses take to the brain?

Blood

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What is more common: viral or bacterial meningitis?

Viral

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What is more severe: viral or bacterial meningitis?

Bacterial

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What is the presentation of meningitis?

Headache
Fever
Neck stiffness
\+/- vomiting
\+/- photophobia

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What is the main viral cause of meningitis?

Enteroviruses

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How do enteroviruses enter the body?

Via mouth

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What are some other viral causes of meningitis, that aren’t enteroviruses?

Mumps
VZV
Influenza
HIV
HSV 2

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What is more severe: viral or bacterial encephalitis?

Viral

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What is the presentation of encephalitis?

Like meningitis, but also

Personality and behavioural changes
Seizures
Partial paralysis
Hallucinations
Altered state of consciousness
Ultimately coma and death

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What are the most common causes of viral encephalitis?

HSV 1 and 2
Rabiesvirus
Arboviruses (insect-borne)
Enteroviruses

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Can mumps virus meningitis also cause encephalitis?

Yes but is generally mild

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What is post-infectious encephalomyelitis?

Occurs few days after infections
No virus present but
- Inflammation
- Demyelination
Possibly autoimmune in nature

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Which viruses can cause post-infectious encephalomyelitis?

Measles
Chickenpox
Rubella
Mumps

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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

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Which viruses can cause Guillain-Barre syndrome?

EBV
CMV
HIV

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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

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What are chronic demyelinating diseases?

Very rare
Eg: sub-acute sclerosing panencephalitis (SSPE)
- Late sequel (30 yrs) to measles infection

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What is AIDS encephalopathy/AIDS dementia complex?

HIV infection > immunodeficiency > neurovirulent

50% of patients develop progressive dementia

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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?

Rabiesvirus 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?

Poliovirus Mumps virus Measles virus Coxsackievirus

How does HIV reach the CNS?

Via monocytes

What structures carry viruses into the CNS?

``` Cerebral blood vessel Direct spread from adjacent structures Meningeal blood vessel Peripheral nerve ending Nasal mucosa Blood vessel in choroid plexus ```

Which viruses enter through the olfactory bulb?

Coronavirus | HSV

Which viruses cause inflammatory diseases?

Those that directly kill neurons

What are the sequelae of extensive loss of neurons because of a viral infection?

``` Mental retardation Epilepsy Paralysis Deafness Blindness ```

Which cells do viruses replicate in that cause demyelination?

Oligodendrocytes

Does the immune response also cause damage during inflammation?

Yes

Does rabiesvirus need nerve cells for its life cycle?

Yes

What is the neuroinvasiveness and neurovirulence of rabiesvirus?

High neuroinvasiveness | High neurovirulence

Describe the structure of rabiesvirus

Bullet shaped -ve ssRNA Helical capsid Envelope

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 Thirst 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 - Death 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?

Yes

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?

HSV 1

Which virus causes genital warts?

HSV 2

What are some viruses that belong to the herpesvirus family?

HSV 1 and 2 | VZV

Do herpesviruses need nerve cells for their life cycle?

Yes

What is the neuroinvasiveness and neurovirulence of herpesviruses?

Low neuroinvasiveness | High neurovirulence

Describe the structure of herpesviruses?

Linear dsDNA Icosahedral Envelope

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?

Gingivostamatitis - 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?

10-15%

What proportion of HSV infections cause inapparent infection in the lymph nodes?

85-90%

What ganglia does HSV inhabit?

HSV 1: trigeminal | HSV 2: sacral

What can reactivate a latent HSV infection?

Stress UV Declining immunity

Where does HSV infect in the CNS?

Neurons and glia in temporal lobe

What is the case fatality rate of HSV encephalitis?

70%

What causes most cases of HSV encephalitis: reactivated or primary infections?

Reactivated

How many people have a latent infection with HSV in their ganglia?

20%

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?

Haematogenously

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 Primary viremia Replication in liver and spleen Secondary viremia

What is the incubation time for VZV?

4-6 days

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?

Low neuroinvasiveness | High neurovirulence

What is the structure of poliovirus?

+ve ssRNA Icosahedral No envelope

What is the genus of poliovirus?

Enterovirus

What familydoes poliovirus belong to?

Picornavirus

Is poliovirus cytocidal?

Yes

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 - Replicates 4. Blood: day 5-15 - Viremia 5. BBB: day 8-12 - Rarely - Crosses 6. Spinal cord: day 10-30 - Replicates in anterior horn cells - Cell destruction - Paralysis 7. Gut: day 5-45 - Normally stays here - Excreted in faeces

How quickly can poliovirus cause total paralysis if it enters the CNS?

Hours

How many cases of polio occur before 3?

50%

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?

Faecal-oral

What causes enterovirus meningitis?

All coxsackie B types Coxsackie A7 and A9 Many echoviruses

When does enterovirus meningitis often occur?

Summer | Autumn

Viruses Affecting the Central Nervous System Flashcards

(97 cards)