Viral transmission and Spread in the Body

Three factors important for initiating an infection:

1.) cells must be susceptible (entry receptor)

2.) cells must be permissive (viral replication)

3.) must be a sufficient number of virions (dose)

susceptibility

cells must have the appropriate receptor that matches a viruses receptor binding protein to allow for entry

permissibility

whether a cell has the internal machinery/conditions necessary for a virus to successfully replicate after it gets inside

Three routes of infection for viruses:

1.) mucosa

2.) eye

3.) skin

Five examples of mucosa routes of infection

-respiratory

-gastro-intestinal

-urogenital

-reproductive

Upon entering, a virus has two fates regarding the type of infection:

1.) local spread

2.) viremic spread

local spread

The virus replicates at its site of entry and then spreads primarily to nearby cells/tissues

Example of a virus with a localized infection

influenza viruses, such as canine influenza

viremic spread

The virus enters the bloodstream, allowing it to travel to distant tissues and organs.

A viremic spread will have two "stages"

1.) Primary viremia

2.) Secondary viremia

Primary viremia

virus first enters the bloodstream after initial replication

Secondary viremia

virus replicates in another tissue/organ and then re-enters the blood in larger amounts, allowing further dissemination

Dissemination

the spread of a virus from its initial site of infection to other tissues or organs throughout the body

Example of a virus with a viremic infection

canine distemper virus

What area of the body is the most common portal of entry for viruses?

the respiratory tract

What is the primary target for viruses infecting the respiratory tract?

epithelial cells that line the respiratory tract

Viruses that survive in lower temperatures will infect the ________ respiratory tract

Viruses that survive in higher temperatures will infect the ________ respiratory tract

upper

lower

Two categories of defense mechanisms of the respiratory tract against viruses:

1.) mechanical barriers

2.) immune responses

Three respiratory tract mechanical barriers against viruses:

1.) ciliated cells

2.) mucus secreting goblet cells

3.) subepithelial mucus-secreting glands

Two respiratory tract immune barriers against viruses:

1.) IgA

2.) IgG

IgA

mucosal immunity; binds viruses before they attach to and infect respiratory epithelial cells

IgG

involved in systemic humoral immunity and is abundant in the blood; neutralizes viruses/toxins and makes them easier for phagocytes to recognize and engulf (opsonization)

Which immunoglobulin is prominent in the upper respiratory tract?

Lower respiratory tract?

Upper respiratory tract: IgA

Lower respiratory tract: IgG

What is the significance of immunoglobulin specificity in the respiratory tract?

Vaccines stimulate IgG and therefore will protect an animal against lower respiratory tract infections, but not upper respiratory tract infections

Examples of the physiological consequences of viral infection in the respiratory tract:

-Destruction of epithelial cells

-Loss of ciliary activity

-Loss of mucus lining

-Inflammation with fluid exudation

-Increased susceptibility to secondary infections (consequence of lung injury and immune suppression)

Two routes of transmission of respiratory tract viral infections:

1.) direct transmission (through secretory droplets + aerosols)

2.) indirect transmission through feed troughs, water bowls, etc

Two routes of infection for the GI tract:

1.) oral infection

2.) hematogenic infection

GI tract routes of infection: oral

The pathogen is ingested and travels through the GI lumen

Oral route of GI tract infection leads to a very _________ incubation period

short

incubation period

interval between initial infection and first signs and symptoms

What protects the host from viruses infecting the GI tract? What type of viruses can bypass these protective mesaures?

acid and bile; naked viruses

GI tract routes of infection: hematogenic

The pathogen enters the body somewhere else, reaches the bloodstream, and then travels through the blood to the GI tract.

Hematogenic spread of a GI tract infection leads to a very _________ incubation period

long

Four defense mechanisms of the GI tract against viral infection:

1.) acid environment in stomach

2.) alkaline environment in the intestine

3.) digestive enzymes

4.) bile enzymes and salts

What type of enveloped viruses can infect the GI tract, despite defense mechanisms? Why?

coronaviruses; milk can buffer GI stomach acid and allow the virus to bypass this defense

The main consequence/symptom of viral infection of the GI tract is _________

diarrhea

Three reasons GI tract viral infection leads to diarrhea:

1.) destruction of epithelial cells (enterocytes) that absorb water/nutrients

2.) intestinal hypersecretion due to nsp4 protein from rotavirus

3.) increased peristalsis due to rotavirus

Viruses that infect the GI tract typically have what route of transmission?

fecal-oral

The skin is the largest "organ" of the body and is usually _________ to viral infection

impermeable

Since the skin is usually impermeable to viral infection, how do viruses infect the skin? (5):

1.) entry through minor abrasions or puncture

2.) arthropod vector

3.) bite of a vertebrate to introduce virus (e.g., rabies)

4.) skin penetration via iatrogenic means

5.) infection after hematogenic spread

iatrogenic means

injections

Three ways viruses shed from the skin:

1.) contact with small abrasions

2.) skin lesions (vesicles and pustules)

3.) feather follicles (Marek's disease virus)

What can lead to infection of a fetus?

systemic infection of the mother leading to transplacental infection

*young, unvaccinated mothers

Consequence of infection of a fetus

fetal death and abortion

Abortion is more common in species which pregnancy is sustained by ________ progesterone rather than ________ progesterone

fetal; maternal

What species have fetal progesterone?

sheep

What species have maternal progesterone?

swine

Immunocompetency of fetus differs according to _________

species

Example of fetal viral infection

equine herpesvirus

equine herpesvirus and fetal infection

-equine herpesvirus can enter a state of latency

-once reactivated, the virus will shed, and may infect a pregnant mare

-when infected by equine herpesvirus, the fetus of a pregnant mare will be aborted

Three routes of infection for CNS viral infection

1.) through the olfactory nerve

2.) through neurons that travel to spinal cord

3.) hematogenic

olfactory nerve

the nerve that carries smell impulses from the nose to the brain

hematogenic infection of CNS

infected leukocytes transport the virus to the brain -OR- active/passive transport through the vascular wall

Most often, CNS infection is a _______ ____

dead end (transmission of the virus does not depend on brain infection)

Exception to CNS infections being a dead end

rabies virus; the virus goes to the brain and can then be transmitted through saliva

In terms of defense mechanisms, the CNS is an immunologically ________ site. Why?

privileged; immune responses within the central nervous system are more restricted and tightly controlled than in most other tissues

**protected from BOTH pathogens and the immune system, meaning it has a reduced immune response (a strong immune response would be detrimental to the brain)

Why does the CNS have a reduced immune response? (2):

1.) astrocytes serve as antigen-presenting cells instead of macrophages or dendritic cells

2.) there is no MHC class I expression on neurons (no CD8 T cells)

Four consequences of CNS infection

1.) transient infection

2.) lytic infection of neurons

3.) non-inflammatory infection

4.) progressive demyelination

transient infection

infection in which the pathogen is present and replicating for a short period of time, and then is cleared from the host

Rabies virus characteristics

-naked/enveloped?

-RNA/DNA genome?

-member of what viral family?

enveloped with RNA genome; member of rhabdovirus family

Transmission of rabies virus

bites from infected animals (saliva)

Steps of rabies infection to the brain:

1.) transmitted via bites from saliva

2.) virus replicates locally in the muscle

3.) virus enters the nerve cells through acetyl-choline receptor

4.) virus migrates within nerves to spinal cord and then the brain

5.) spreads to the eyes and salivary glands

Two types of rabies cycles:

1.) domestic/urban

2.) sylvatic

domestic/urban cycle of rabies

infects dogs

sylvatic cycle of rabies

infects wildlife, including:

-racoons

-skunks

-red foxes

-silvertailed bat

Three phases of rabies virus:

1.) prodromal phase

2.) excitative phase

3.) paralytic phase

prodromal phase of rabies virus

first phase; unspecific symptoms (headache, fever, lethargy, inappetance, etc)

excitative phase of rabies virus

-anorexia

-hyperexcitability

-aggression

paralytic phase of rabies virus

end stage of rabies; as virus enters the brain, animal becomes very apathetic and paralytic

Immediate treatment of rabies

washing of wound with detergent (physically removes the virus)

Post-exposure treatment of rabies

injection of rabies-specific IgG (passive immunity) and vaccination (active immunity)