NP4C Flashcards
Viruses can infect cells, but to do so we need to have:
- appropriate receptors on neurons or glia
- receptors expressed at points of viral entry (entry at the periphery and points of entry into the CNS)
- appropriate metabolic environment within the target cell to support replication
If a virus can infect nervous tissue and cause disease under natural conditions, it is said to be___________
neurovirulence
Sometimes neurovirulence is restricted to a __________or _________ because the blood-brain barrier is not mature, the animal is not fully immune competent, and there may be cells undergoing high rates of proliferation that provide a fertile metabolic environment for viral replication.
neonate, fetus
This was the case in BVDv and feline panleukopenia virus infections responsible for developmental disorders. We refer to these as ___________ because they are targeting cells simply because of the fact that they are replicating – mimicking the effects of radiation exposure.
radiomimetic agents
One of the major receptors used by rabies virus (RABV) is the ______________ , which is expressed in both the central and peripheral nervous system.
(nicotinic) acetylcholine receptor
RABV also enters neurons in ____________ sensory receptors in muscle, using a nerve growth factor receptor that is responsible for the health of neurons.
spindle-shaped
Once in the neuron, the virus is transported centrally using axoplasmic transporters. Viral variants exist, coming from distinct animal reservoirs. If the ________________, it will do minimal structural damage to neurons and elicit a minimal inflammatory response, allowing the virus to complete its life cycle.
Virus is well-adapted to host
the professional CNS pathogen
Rabies Virus
A serum that can only neutralize virus between the time you were bitten and the time required for the virus to enter a nerve ending. Once within the axon, it is shielded. The timeline can be variable – as long as a couple of days
hyperimmune serum
What about inhalation of aerosolized virus (e.g., from bat guano)?
- Transmission of olfactory neurons to forebrain shortens the process, such that behavioral changes and death will likely occur before salivary tissues are exposed – shedding of virus is unlikely.
- There is no treatment for rabies encephalitis.
What do tissues look like? (Rabies)
- Inclusions in the cytoplasm of neurons. These are “viral factories” – aggregates of viral genomes that are being transcribed and replicated. These inclusions have a name that is specific for rabies – Negri bodies.
- Evidence of neuronal death
- Non-suppurative inflammation should also be present.
- Confirmatory testing stains for viral antigen
These viruses cause neuronal death and inflammation right from the start. The virus never made it into the spinal cord. There were no inclusions – the viral factory closed early. There is no shedding of infectious viruses. The cycle was not completed.
The virus that is not well adapted to its host
Is a paramyxovirus closely related to the measles virus, and both have a similar approach to infecting the respiratory tract – their major goal.
Canine distemper virus (CDV)
Canine distemper virus – the accidental tourist:
Initial replication is in airway-associated __________, shedding progeny virus into the blood stream (primary viremia).
lymphoid tissue
Virus can infect olfactory neurons, and from there travel into the brain via olfactory nerves
Canine distemper virus – the accidental tourist
In dogs, the virus is rapidly cleared from the CNS in most cases, but problems can arise
CDV
In very young puppies that do not have passively acquired immunity from the dam, high levels of virus enter the CNS and neurons at this age are highly permissive to infection. The virus spreads rapidly through tissue causing death. The permissiveness of immature neurons to virus replication and an antiviral immune response that is not fully developed means that you may see very little inflammation. Neurons will have both __________ and ___________inclusions – they are functioning as great viral factories.
cytoplasmic, intranuclear
What is you only see cytoplasmic inclusions?
You would have to have rabies in the differential list
In diagnosing a viral infection, look for a _____________ (something targeting a specific cell type that would indicate a preference of the virus, such as a tropism for neurons)
selective insult
(true/false) Inclusions are great if you have them, but they don’t always form, in which case you may simply have selective necrosis
true
What is a good change to look for?
Non-suppurative (lymphocytic) inflammation is the other change to look for. It might be very limited in amount, but that is the exception rather than the rule.
acute encephalopathy is characterized by neurons with prominent intranuclear inclusion bodies
young puppies
subacute leukoencephalitis with astroglial intranuclear and cytoplasmic inclusion bodies and primary demyelination
adult dogs
Neuronal necrosis and no cytoplasmic inclusion are an example of what?
Describes an infection where the virus is poorly adapted to the host
