Viral CNS infections Flashcards
Which viruses can affect the CNS? (6)
Herpes
Entero viruses
Arbo viruses
measles
Rabies
(unconventional agents)
What are the steps required for neural virus infection? (4)
Where does the viral replication occur?
- Entery: depending on the site of infection, could enter the neuron at the axon, sensory terminal or cell body
- Transport: the virus particle or subviral particle –> the neuronal cell body where the virus replication occurs
- Replicate of the virus genome (@ the neuronal cell body)
- Assembly of the virus particles that EGRESS from the infected neuron in a directional matter
Define the following:
Encephalitis
Myelitis
Meningitis
Encephalomyelitis
Encephalopathy
Encephalitis - inflammation of the CNS
Myelitis - inflammation of the white matter/spinal cord
Meningitis (includes pia matter and choroid plexus)- inflammation of the meningeal layer
Encephalomyelitis - combo inflammation
Encephalopathy -brain pathology without inflammation
What are the different access routes to the CNS:
What two important properites are needed to establish CNS infection?
Access routes include hematogenous routes to CNS, direct infection of peripheral neurons, infection of olfactory neurons (which are part of CNS), infection into the meninges from hematogenous sources.
Note that infection and disease depends on the two distinct properties of neuroinvasiveness (ability of virus to access CNS) and neurovirulence (ability of virus to cause disease once in CNS, either by directly infecting and destroying cells of CNS, and / or by stimulating pathogenic immune responses in CNS)
What type of infection is herpes in the CNS?
neurotropic entry route
displays neuroinvasiveness
This requires that viruses enter neurons, usually at termini, then transport to cell bodies, replicate, assemble and egress. For dissemination of viruses throughout the CNS parenchyma, these processes are directional (through neural connections).
What are the traditional host cells for herpes infection? (2)
How does the herpes infection enter the CNS? What is unique about this entry point?
Ehpithelial cell
Peripheral neurons of te basal ganglia
Rare CNS entry may be through olfactory neurons and then to deeper CNS regions via retrograde transport in axons
olfactory neurons are unique CNS cells because their dendrites are exposed in the olfactory epithelia
The herpes viruses can transport bidirectionally, and this property sets them apart from other neurotropic human viruses
Herpes CNS infections are fatal in about 40%
- Often latent in neurons, but can be reactivated
- Reactivated virus transport to epithelia (as depicted here) — epithelial lesions
- Reactivated virus transport into CNS — lethal encephalitis
How does herpes reactivation occur?
In normal herpes infections, only a very small number if ganglial cells are productively infected. Latent infection is more common.
The latently infected cell harbors episomal HSV DNA. Such latently infected cells do not die. Rare virus activation (the term “activation” here refers to HSV gene expressions) will begin to make virus particles. Manufacture of HSV particles is cytolytic.
The cells survive long enough to transmit viruses back to epithelium, re‐seeding earlier sites of HSV infection (note that cold sores can reappear in same sites years after original infection)
Herpes CNS infections are fatal in about 40%.
How can it be diagnosed?
Is there any treatment?
Spinal Tap is necessary –> PCR
Elevated leukocytes in CSF, (not as high as meningitis) but such elevation may not be observed in peripheral blood
TX: IV, high dose acyclovir
Where does herpes virus like to infect?
Temporal lobe
What is unique about arboviruses?
What is the course of the infection vs host defense?
They have 2 different hosts - insects and mammals
Virus replicated in the insect and is then redelivered to the host
Infection:
- Skin is inoculated by inset
- Infection of skin dendritic cells (interferon RNA interference can eliminate the virus here)
- infection of the lymph node
- Viremia (neutralizing antibodies, complement, NK cells)
- CNS entry, infecting cells of the meningeal layer (Cytotoxic T lymphocytes)
WNV is the most common arbovirus in our area.
Why is the infection refered to as “incidental” ?
The WNV transmission cycle is typically from mosquito to bird and back, but rarely extends to human, or horse, or other large mammals. This transmission to humans typically breaks the virus transmission chain. That is why infection is termed “incidental” here. The virus gets in the bloodstream and then infects the meningeal layers. The disease is an immunopathology, little virus replication but extreme immune response.
Reservoir: BIRD
Vector: MOSQUITO
Who is at highest risk for WNV?
adults > 50 y/o and immunocompromised
symptoms include: fever, h/a, stiff neck, disorientation, muscle weakness and paralysis
What are the 3 forms of measles involvement in the CNS and their etiologies?
1. Acute postinfectious encephalitis: no detectable virus, rash, perivascular inflammatory changes and demyelination; postulated AI reaction against brain tissue
2. Acute progressive infectious encephalitis: Presence of complete virus –> cytolytic replication in brain tissue –> inflammation; due to absence of normal cell-bound immunity
3. Subacute Sclerosing Panencephalitis: many years post dz; presence of viral inclusion bodies in brain cells – inflammation – general destruction of brain tissue –> progressive dissemination of a defective virus infection in the presence of a normal immune response - no production of infectious extracellular particles
How does a rabies infection occur?
where does replication occur?
What is unique about the pathogenesis of rabies?
- virus enters tissue from saliva of bitting animal
- virus replicates in muscle near bite
- virus moves up peripheral nervous system to CNS in spinal cord
- Virus ascends spinal cord
- virus reaches the brain and causes fatal encephalitis
- virus enters salivary glands and other organs of the victim
UNI-directlional/retrograde transport from peripheral sites to teh CNS
What is the average incubation period for someone infected by rabies?
When do first symptoms appear. What are some sx?
What are the other steps of rabies infection/progressing?
incubation: 20-90 days
Prodrome – when symptoms first appear
2-10 days
sx: fever, anoreia, n/v, h/a, malaise, lethary, pain or parathesias at bite
Acute neurological phase (2-7 days)
when first neurological sign appear (fear of swallowing water)
Coma (0-14 days)
Several months –> death or recovery.
