Viruses affecting the CNS

Question 1

Neurotropic virus?

Answer 1

capable of REPLICATING in nerve cells

Question 2

Neuroinvasive virus?

Answer 2

capable of entering or infecting the CNS

Question 3

Neurovirulent virus?

Answer 3

capable of causing disease within the nervous system

Question 4

meningitis?

Answer 4

infection of the meninges surrounding the brain and spinal cord

Question 5

encephalitis?

Answer 5

an infection of the brain itself

Question 6

myelitis

Answer 6

an infection of the spinal cord

Question 7

encaphalomyelitis

Answer 7

both brain and spinal cord infection

Question 8

primary viral encephalitis/acute viral encephalitis

Answer 8

direct viral infection of the spinal cord and brain. can be focal or diffuse.

Question 9

secondary encephalitis, aka post-infectious encephalitis

Answer 9

results from complications of a current viral infection that spreads to the brain, usually via the blood

Question 10

main causative pathogen of viral meningitis?

Answer 10

enteroviruses (enter the body via mouth). also caused by mumps, varicella zoster, influenza, HIV and herpes simplex type II (genital herpes)

Question 11

main causative pathogen of viral encephalitis?

Answer 11

herpes simplex virus type I and II. rabies virus, arbo viruses (insect-borne viruses), and enteroviruses

Question 12

how does viral meningitis typically present in patients?

Answer 12

neck stiffness, headache, fever, with or without vomiting and/or photophobia

Question 13

main causative pathogen of viral encephalitis?

Answer 13

herpes simplex virus type I and II. rabies virus, arbo viruses (insect-borne viruses), and enteroviruses.

(mumps encephalitis may also involve the brain parenchyma, but usually mild).

Question 14

how does viral meningitis typically present in patients?

Answer 14

neck stiffness, headache, fever, with or without vomiting and/or photophobia

Question 15

how does viral encephalitis present in patients?

Answer 15

presents like meningitis with neck stiffness, headache and fever. but also develops personality and behavioral changes, seizures, partial paralysis, hallucinations, altered levels of consciousness –>ultimately coma and death

Question 16

what are the common causative agents behind post-infectious encephalomyelitis?

Answer 16

may occur in the wake of measles, chickenpox, rubella, or mumps.
The virus is not present, but inflammation and demyelination is evident.
Possible to be autoimmune in nature.

Question 17

Guillain Barre syndrome pathogenesis?

Answer 17

• acute inflammatory demyelinating disease following infection with viruses such as EBV, CMV, HIV
• results in partial or total paralysis, but with total regain of function in 75% of cases

Question 18

Reye’s syndrome pathogenesis?

Answer 18

post-infection with influenza or chickenpox.
CEREBRAL OEDEMA, but not inflammation.
NB: Associated with administration of aspirin during initial fever.

Question 19

chronic demyelinating disease features?

Answer 19

Very rare. exemplified by Sub-acute sclerosing panencephalitis (SSPE), a late sequel to measles infection.

Question 20

AIDS encephalopathy (AIDS dementia complex)

Answer 20

once HIV infection leads to immunodeficiency, the HIV becomes neurovirulent.
50% of patients develop progressive dementia.

Question 21

how do viruses exploit the PNS to breach the BBB and infect the CNS?

Answer 21

Nerve cells do not have MHC class I receptors! uncoated nucleocapsids or whole virions can travel passively along the axon or dendrites from the peripheral tissues into the CNS.

ex. rabies virus, yellow fever virus, herpes simplex type I and II

Question 22

where do neurotropic viruses replicate?

Answer 22

body of the nerve (soma) b/c this is where protein synthesis takes place.

released progeny can then cross the synaptic junction.

Question 23

how might viruses reach the CNS via the blood? examples of viruses?

Answer 23

once already in the blood, viruses might reach the CNS (brain) via a meningeal blood vessel.

poliovirus, mumps, measels, coxsackie, and HIV (in monocytes)

Question 24

describe structure of rabies virus?

Answer 24

Rabies is a bullet-shaped, negative-stranded RNA virus, with helical capsid and an envelope.

Question 25

describe life cycle and pathogenicity of rabies virus

Answer 25

Highly neurovirulent and highly neuroinvasive. Obligatory neurotropic virus. 1. virus enters muscle via bite of rabid animal. 2. replicates in myocytes of striated muscle 3. enters PNS nerve ending, carried via axoplasmic flow to spinal cord (8-20mm/day) 4. virus travels along neural process and replicates in CNS. 5. travels from CNS along peripheral nerves to the salivary gland 6. replicates in salivary acinar cells, virus is discharged in saliva **70-day Cycle

Question 26

structure of herpes simplex virus type I and II? (varicella zoster virus)

Answer 26

Linear dsDNA genome, icosohedral, sorrounded by envelope. Obligatory neurotropic virus. Low neuroinvasiveness. High neurovirulence.

Question 27

life cycle and pathogenicity of Herpes Simplex type 1 and 2

Answer 27

HSV-1 enters body through contact with infected saliva, primary infections involve mouth and/or throat. HSV-2 enters through mucous membrane of genital region. A) 15% of cases: Follow primary disease route, enters adjacent nerve endings to enter sensory nerve ganglia (trigeminal for HSV-1, or sacral for HSV-2). Remains a latent infection until a stressor event reactivates virus, migrates along axon, leading to localized multiplication and disease recurrence at trigeminal or sacral nerve endings. In rare cases, it may enter blood and distant organs, causing severe sporadic encephalitis (infected neurons and glia in the temporal lobe). 70% case fatality rate. B) 85% of cases: Undergo local replication in regional lymph nodes, and infection eventually gets cleared. In rare cases, virus can also enter blood from lymph nodes and cause severe sporadic encephalitis.

Question 28

majority of fatality's of HSV-1 and HSV-2 related severe sporadic encephalitis are primary cases or reactivated cases?

Answer 28

Reactivated cases.

Question 29

how is the HSV viral genome maintained in latency?

Answer 29

20% people harbour latent genome in ganglia. Genome is maintained as an episome (circular piece of DNA) coated with histones. They express a latency activated mRNA transcript (LAT's). CD8+ T cells may be responsible for keeping genome in dormant state.

Question 30

which conditions does varicella zoster cause?

Answer 30

chicken pox (varicella) and shingles (zoster)

Question 31

describe pathogenesis of chickenpox (varicella)

Answer 31

-viral infection of conjuctiva/and or mucosa of URT. - replication in regional lymph nodes. - ->primary viremia in blood stream. - further viral replication in liver and spleen - ->secondary viremia - infection of skin, and appearance of vesicular rash. - ->scratching of rash releases virus into the air. **VIRAL SPREAD IS HEMATOGENOUS. 10-DAY CYCLE.

Question 32

describe pathogenesis of shingles (herpes zoster )

Answer 32

following primary infection with chickenpox (varicella), virus may travel to dorsal root ganglion and remain latent. -->reactivation causes herpes zoster vesicles following a dermatome path. **Tx with Acyclovir ASAP*

Question 33

describe the structure of poliovirus?

Answer 33

Poliovirus is a + stranded RNA virus with an icosahedral capsid and no envelope. Member of Enterovirus genus of the Picornavirus family (small RNA viruses).

Question 34

pathogenisis of poliovirus?

Answer 34

Low Neuroinvasiveness and High Neurovirulence. NOT an obligatory neurotropic virus. Cytocidal, kills cells it replicates in. 1. virus ingested from water/food contaminated with feces 2. reaches GALT (gut associated lymphoid tissue). invades tonsils and peyers patches. 3. replicates in regional lymph nodes 4. enters blood stream, causes plasma viremia 5. crosses BBB 6. replicates in anterior horn cells of spinal cord, causes cell lysis 7. reaches gut, excreted in feces * *targeting of ventral horn motor cells causes paralysis * *if CNS is targeted, total paralysis may occur in a matter of hours

Question 35

T/F

Answer 35

TRUE

Question 36

T/F in polio infection, lower limbs are more frequently affected than upper limbs?

Answer 36

TRUE. "Acute flaccid paralysis."

Question 37

in which polio cases is the mortality rate greatest?

Answer 37

when virus affects brain stem motor neurons, impacting breathing centres.

Question 38

how do coxsackie virus type A and B, and echoviruses spread?

Answer 38

``` via fecal/oral route. circulate in the blood to target organs. -->Brain (encephalitis, paralysis) -->Meninges (meningitis) -->Skin (hand, foot, mouth disease) -->Muscle (myocarditis, endocarditis, pleurodynia) ```