Viruses affecting the Central Nervous System

Question 1

What does neurotropic mean?

Answer 1

Capable of replicating in nerve cells

Question 2

What does neuroinvasive mean?

Answer 2

Capable of entering or infecting the central nervous system

Question 3

What does neurovirulent mean?

Answer 3

Capable of causing disease within the nervous system

Question 4

What is meningitis?

Answer 4

Infection of the meninges, the membranes that surround the brain and spinal cord

Question 5

What is encephalitis?

Answer 5

Inflammation of the brain itself

Question 6

What is myelitis?

Answer 6

An infection of the spinal cord.

Question 7

What is encephalomyelitis?

Answer 7

When both the brain and the spinal cord become inflamed

Question 8

What is primary viral encephalitis (also called acute viral encephalitis)?

Answer 8

Direct viral infection of the spinal cord and brain.

Can be focal or diffuse.

Question 9

What is secondary encephalitis (aka post-infectious encephalitis)?

Answer 9

The result of complications from a current viral infection where virus spreads to the brain, usually via the blood

Question 10

What is more common, viral or bacterial meningitis?

Answer 10

Viral is more common but less severe

Question 11

How does viral meningitis present?

Answer 11

Headache

Fever

Neck stiffness

With or without vomiting and/or photophobia

Question 12

What are the common causes of viral meningitis?

Answer 12

Enteroviruses (common viruses that enter the body through the mouth)

Question 13

What are less common causes of viral meningitis?

Answer 13

Mumps

Varicella zoster

Influenza

HIV

Herpes simplex type 2 (genital herpes)

Question 14

What is one of the most serious viral diseases?

Answer 14

Viral encephilitis

Question 15

How does viral encephalitis present?

Answer 15

Like meningitis

But also personality and behavioural changes, seizures, partial paralysis, hallucinations, and altered levels of consciousness

Ultimately coma and death.

Question 16

What are the common causes of viral encephalitis?

Answer 16

Herpes simplex virus types 1 and 2

Rabiesvirus

Arboviruses (insect-borne viruses)

Enteroviruses

Question 17

When does post-infectious encephalomyelitis occur?

Answer 17

A few days after infections such as measles, chickenpox, rubella or mumps

Question 18

What is present in postinfectious encephalomyelitis?

Answer 18

No virus present but inflammation and demyelination are evident

Question 19

What is Guillain-Barre syndrome?

Which viruses can cause this?

Answer 19

Acute inflammatory demyelinating disease

EBV, CMV, HIV

Question 20

What does Guillain-Barre syndrome result in?

Answer 20

Partial or complete paralysis

Most people (75%) fully recover within weeks

Question 21

Does Guillain-Barre require active infection for an outbreak to occur?

Answer 21

No

Question 22

What is Reye’s syndrome?

Answer 22

A post-infection from influenza or chickenpox in children leading to cerebral oedema.

Question 23

What happens to the brain in Reye’s syndrome?

Answer 23

Cerebral edema but no inflammation

Question 24

What is Reye’s syndrome epidemiologically associated with?

Answer 24

Administration of aspirin during initial fever

Question 25

What are chronic demyelinating diseases exemplified by?

Answer 25

Sub-acute sclerosing panencephalitis (SSPE), a late sequel to measles infection

Question 26

How do viruses spread to the brain?

Answer 26

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.

Question 27

How are viruses protected from attack by nerve cells?

Answer 27

Neurons lack MHC Class I molecules, therefore viruses are protected from attack by CTL.

Question 28

Where in the nerve does viral replication take place?

Answer 28

In the body of nerve as this is where protein synthesis takes place

Question 29

Can the released viral progeny cross the synaptic junction?

Answer 29

Yes

Question 30

How does retrograde viral spread occur?

Answer 30

Uptake at axon Transport up axon Replication in soma Transsynaptic spread Transport up axon Replication

Question 31

How does anterograde viral spread occur?

Answer 31

Uprake and replication in soma Transport down axon Transsynaptic spread Tansport down axon

Question 32

Can other viruses enter the CNS directly via the blood stream like in other tissues?

Answer 32

Yes E.g. poliovirus, mumps virus, measles virus, coxsackievirus; also HIV in monocytes

Question 33

Can viruses enter via the olfactory bulb?

Answer 33

Yes Coronavirus, herpes simplex virus

Question 34

What are the two possible effects viruses can have once in the brain?

Answer 34

1. **Killing neurons** directly (inflammatory disease) leading to mental retardation, epilepsy, paralysis, deafness or blindness. 2. Replication in non-neuronal cells (e.g. oligodendrocytes) causing **demyelination**.

Question 35

What happens to the blood-brain barrier during inflammation?

Answer 35

Lymphocytes, antibodies and other immune effectors can enter

Question 36

What is an obligatory part of the rabiesvirus life cycle?

Answer 36

Growth in nerve cells

Question 37

Why can rabiesvirus enter the CNS?

Answer 37

High neuroinvasiveness and high neurovirulence

Question 38

What are the physical characteristics of rabiesvirus?

Answer 38

Bullet-shaped –ve stranded RNA virus Helical capsid and an envelope

Question 39

Does rabiesvirus hide from the immune system in nerve cells?

Answer 39

No

Question 40

What does rabiesvirus replication in the nerve cell body lead to?

Answer 40

Rabies glycoprotein displayed on the cell surface

Question 41

What are the signs and symptoms of rabiesvirus infection?

Answer 41

Aggression Thirst but muscle spasm and terror upon attempt to drink water

Question 42

What is the pathogenic mechanism of rabiesvirus?

Answer 42

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

Question 43

What comprises the alpha herpesviruses?

Answer 43

Herpes simplex viruses 1 and 2 (HSV) Varicella-zoster virus (VSV)

Question 44

What is an obligatory part of the alpha herpesvirus life cycle?

Answer 44

Growth in nerve cells

Question 45

What is the neuroinvasiveness and neurovirulence of alpha herpesviruses?

Answer 45

Low neuroinvasiveness High neurovirulence

Question 46

What is the genetic structure of alpha herpesviruses?

Answer 46

Linear dsDNA genome

Question 47

What is the physical structure of alpha herpesviruses?

Answer 47

Icosahedral and surrounded by an envelope

Question 48

What is the normal maintenance cycle of alpha herpesviruses?

Answer 48

Infects mucosal surfaces and then enters latent infection in sensory and autonomic ganglia. Possibility for viraemia.

Question 49

What is the pathway leading to serious disease from alpha herpesviruses?

Answer 49

Primary infection leads to viraemia and disseminated infection that can infect CNS. Infection in sensory/autonomic ganglia leads to CNS infection.

Question 50

How does HSV 1 enter the body?

Answer 50

Through contact with infected saliva.

Question 51

Which region of the body do primary herpes simplex type 1 viruses typically involve?

Answer 51

The mouth and/or throat

Question 52

What is the pathogenesis of herpes simplex virus type 1?

Answer 52

See image

Question 53

What percentage of people harbour the latent herpes simplex 1 virus in their ganglia?

Answer 53

20%

Question 54

How is herpes simplex 1 genome maintained during latency?

Answer 54

As an episome coated with histones

Question 55

Is there any structural gene expression during latency of HSV1?

Answer 55

No

Question 56

What is expressed during HSV1 latency?

Answer 56

2kb latency activated mRNA transcripts (LATs)

Question 57

What is varicella-zoster virus the cause of?

Answer 57

Chicken pox (varicella) Shingles (zoster)

Question 58

How does VZV spread during chickenpox?

Answer 58

Hematogenous (by the blood) Virus subsequently enters the nerves from the resulting vesicular rash.

Question 59

What happens during chickenpox?

Answer 59

See image

Question 60

What happens during the reactivation phase of VZV that results in shingles?

Answer 60

Recurrent infection of VZV causes painful blisters of shingles that follow a dermatome.

Question 61

Is growth of poliovirus in nerve cells an obligatory part of the life cycle?

Answer 61

No

Question 62

What is the neuroinvasiveness and neurovirulence of poliovirus?

Answer 62

Low neuroinvasiveness High neurovirulence

Question 63

What is the physical structure of poliovirus?

Answer 63

+ve stranded RNA virus Icosahedral capsid and no envelope

Question 64

What effect does poliovirus have on the cells it's in?

Answer 64

Kills them (cytocidal virus)

Question 65

Which family does poliovirus belong to?

Answer 65

Picornavirus

Question 66

What is the pathogenesis of poliovirus?

Answer 66

Poliovirus travels in the blood as free virus and can target the motor neuron cells in the anterior horn leading to paralysis (see image).

Question 67

What may poliovirus cause within hours if it invades the CNS?

Answer 67

Paralysis

Question 68

Which neurons does poliovirus kill?

Answer 68

Motoneurons

Question 69

True or false: the majority of poliovirus infections lead to irreversible paralysis.

Answer 69

False Less than 1% of infections lead to irreversible paralysis

Question 70

Which limbs are more affected in poliovirus infections?

Answer 70

Lower limbs are affected more often than the upper limbs, leading to acute flaccid paralysis.

Question 71

Which enteroviruses lead to meningitis?

Answer 71

All coxsackie B types, coxsackie A7 and A9 many echoviruses

Question 72

What is the pathogenesis of enteroviruses?

Answer 72

Primary viraemia in circulation leads to secondary viraemia in target tissues, such as brain, meninges, liver, skin and muscle (see image).