NP4C

Question 1

Viruses can infect cells, but to do so we need to have:

Answer 1

• 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

Question 2

If a virus can infect nervous tissue and cause disease under natural conditions, it is said to be___________

Answer 2

neurovirulence

Question 3

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.

Answer 3

neonate, fetus

Question 4

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.

Answer 4

radiomimetic agents

Question 5

One of the major receptors used by rabies virus (RABV) is the ______________ , which is expressed in both the central and peripheral nervous system.

Answer 5

(nicotinic) acetylcholine receptor

Question 6

RABV also enters neurons in ____________ sensory receptors in muscle, using a nerve growth factor receptor that is responsible for the health of neurons.

Answer 6

spindle-shaped

Question 7

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.

Answer 7

Virus is well-adapted to host

Question 8

the professional CNS pathogen

Answer 8

Rabies Virus

Question 9

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

Answer 9

hyperimmune serum

Question 10

What about inhalation of aerosolized virus (e.g., from bat guano)?

Answer 10

• 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.

Question 11

What do tissues look like? (Rabies)

Answer 11

• 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

Question 12

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.

Answer 12

The virus that is not well adapted to its host

Question 13

Is a paramyxovirus closely related to the measles virus, and both have a similar approach to infecting the respiratory tract – their major goal.

Answer 13

Canine distemper virus (CDV)

Question 14

Canine distemper virus – the accidental tourist:
Initial replication is in airway-associated __________, shedding progeny virus into the blood stream (primary viremia).

Answer 14

lymphoid tissue

Question 15

Virus can infect olfactory neurons, and from there travel into the brain via olfactory nerves

Answer 15

Canine distemper virus – the accidental tourist

Question 16

In dogs, the virus is rapidly cleared from the CNS in most cases, but problems can arise

Answer 16

CDV

Question 17

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.

Answer 17

cytoplasmic, intranuclear

Question 18

What is you only see cytoplasmic inclusions?

Answer 18

You would have to have rabies in the differential list

Question 19

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)

Answer 19

selective insult

Question 20

(true/false) Inclusions are great if you have them, but they don’t always form, in which case you may simply have selective necrosis

Answer 20

true

Question 21

What is a good change to look for?

Answer 21

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.

Question 22

acute encephalopathy is characterized by neurons with prominent intranuclear inclusion bodies

Answer 22

young puppies

Question 23

subacute leukoencephalitis with astroglial intranuclear and cytoplasmic inclusion bodies and primary demyelination

Answer 23

adult dogs

Question 24

Neuronal necrosis and no cytoplasmic inclusion are an example of what?

Answer 24

Describes an infection where the virus is poorly adapted to the host