L12: Viral CNS infections Flashcards Preview

Medical Virology (UoG) Midterm 2 > L12: Viral CNS infections > Flashcards

Flashcards in L12: Viral CNS infections Deck (20):

What are the 4 distinct viral CNS inflammatory sites?

- Meningies (tissue covering brain and SC)
- brain parenchyma (causes encephalitis)
- SC (myelitis)
- Spinal nerve roots (shingles)


What is neurotropism?

The ability for a virus to infect neural cells


What is neuroinvasiveness?

The ability for a virus to enter the CNS


What is neurovirulence?

The ability for a virus to cause disease of neural tissues once it enters the CNS


Fun facts about rabies:
- sense/genome type
- zoonotic?
- Shape
- important protein(s)
- site of replication
- # of serotypes

- sense/genome type = -ssRNA
- zoonotic? = Yes, one of the oldest zoonotic infections
- Shape = bullet (EM)
- important protein(s) = G surface glycoprotein (attachment and fusion)
- site of replication = neurons
- # of serotypes = 1! Ag variation among strains


How is rabies transmitted?

- Through saliva
- Latrogenic (often in corneal transplants)
- Very rarely aerosolised however cases have been documented


Common signs of rabies infection include...

- Nocturnal animals awake during the day
- difficulty walking, eating, drinking
- Animals that tear or scratch at an old wound
- Excitement or viscousness in a usually tame animal
- bold, friendly or apparently tame wild animals


What makes rabies so dangerous in humans?

- Fatality, without intervention, if pretty much 100%
- Virus travels exclusively through neurons (not detected in blood, urine, faeces)


Briefy explain rabies diesease progression.

- Rabies enters body usually through bite
- replicates in muscle near entry point
- virus spreads to motor nerves and enters CNS
- travels through nerve cells (can take weeks to months depending on location of the bite) ****Note: post-exposure vaccinations only effective if virus has not yet reached nerve cells
- Virus replicates further in SC
- paralysis, coma, death

Note: when virus enters brain = 'mad dog' behaviour begins AND when reaches salivary glands, hypersalivation occurs and transmission can occur


How is rabies diagnosed in humans?

- Histopathology --> look for negri bodies (classic sign of rabies infection - present in 71% of cases)
- Virus cultivation --> more definitive diagnosis, use animals models and examine brain immunofluorescence post mortem
- Serology --> ELISA,
- Rapid virus Ag detection --> IFA


What is a prion?

An infectious agent made solely of protein (i.e. doesn't have genetic material)


Describe the course of poliovirus infection.

- virus is ingested
- replication occurs in oropharyngeal and intestinal mucosa (virus shedding in faeces)
- virus drains to lymph notes and to blood = transient viraemia
****After this, most infections are cleared
- Replication occurs at extraneural sites (skeletal muscle, etc.)
- in 1-2% of infected individuals, CNS entry occurs
- replication occurs in motor neurons (SC), brainstem or motor cortex
- Paralysis can occur as a result of replication in motor neurons


Describe the different polio vaccines (2).

Inactivated polio vaccine
- Formalin killed virus
- Contained 3 serotypes
- Highly effective although multiple doses needed
- Not effective in tropical climates due to interaction with other enteric viruses
- Difficult to produce in large quantities

Oral polio vaccine
- Live-attenuated
- Contains 3 serotypes
- Risk of reversion
- Multiple doses needed to be highly effective


What is the significance of vaccine derived poliovirus (VDPV)?

OPV often used in developing countries but since it's replication competent and virus sheds for about 6 weeks post immunisation, need a huge portion of the population to receive the vaccine in order to actually create herd immunity. Replication competent also means mutation competent as well --> this is what happened with type 2 where it reverted back to wt and created VDPV. Consequently, there is increased reliance on inactivated vaccine to maintain immunity


Give 4 examples of prion diseases.

- Kuru
- Scrapie
- Creutzfeld-Jakob disease (CJD)
- Bovine spongiform encephalopothy (mad cow disease)


What are the prion isoforms and how do they differ from each other?

PrP = prion protein

Isoform 1 = PrP(C) = cellular form = very few B-sheets, not protease resistant, detergent soluble

Isoform 2 = PrP(Sc) = scrapie form (from sheep disease) = about 40% B-sheets, partially protease resistant, insoluble in detergent **these are the infectious ones**


How do PrP(Sc)'s replicate?

By imprinting their structure onto an otherwise healthy PrPs --> shape change is enough to go from C isoform to Sc


What makes prion diseases so dangerous?

- We know nearly nothing about prions
- No inflammatory response
- Causes destruction of CNS
- prions can cross BBB


What histological similarity is there between all prion diseases?

They cause big old holes in your brain tissue


What are the key differences (4) between CJD and vCJD?

- vCJD affects younger people
- vCJD duration is longer (up to 2 years between onset and death whereas in sporadic form is < 6 months)
- vCJD typically has behavioural/psychiatric manifestation, commonly depression
- vCJD prions can be detected outside brain in nervous system and lymphoid tissue