Virus Pathogenesis Flashcards
virulence
measure of the degree of pathogenicity
T/F the higher the ID50 and LD50, the more virulent the organism.
F: less virulent
possible outcomes of virus-host interactions
- exposure without infection
- subclinical infection
- mild disease
- moderate disease
- severe disease
- death!!!!
pathogenesis of viral infection
- entry of viruses and primary replication
- spread, tropism, infection of target organs
- virus-cell interactions, secondary replication
- tissue and organ injury
- shedding
- death
skin defenses
- dense outer layer of keratin
- low pH
- presence of fatty acids
- bacterial flora
- dryness
- innate and adaptive immunity (migratory DC = Langerhans cells)
What route does blue tongue virus use to enter a host?
bite of arthropods (culicoides)
3 mucous membranes that can serve as routes of entry?
- conjunctiva
- oropharynx
- genitourinary tract
mucous membrane defenses
IgA
virucidal proteins
GI tract defenses
- mucous membrane of oral cavity and esophagus
- acidity of stomach
- alkalinity of intestine
- layer of mucus covering gut
- lipolytic activity of bile
- proteolytic activity of pancreatic enzymes
- defensins
- IgA
- scavenging macrophages
Respiratory defenses
- mucociliary blanket (moves stuff along)
- alveolar macrophages
- NALT
- BALT
- temp gradient
What facilitates viruses reaching the subepithelial layers?
- inflammatory response to virus and/or destruction of epithelium
- transport pathways like transcytosis
disseminated infection
infection spreads beyond the primary site of infection
systemic infection
if a number of organs or tissues are infected
What kind of release facilitates virus dispersal?
apical release
What kind of release facilitates systemic spread?
basolateral release
lymphatic spread
targeted migration and replication of virus within phagocytic leukocytes, specifically DC and macrophages, lymphocytes
viremia
presence of virus in the blood; may be free in blood or in a cell (lymphocyte)
primary viremia
initial entry of virus into blood after infection
secondary viremia
virus has replicated in major organs and once more entered circulation
passive viremia
direct inoculation of virus in blood
Examples of passive viremia?
bite of arthropods or contaminated syringe
active viremia
viremia following initial virus replication in host; release of virions from initial site of replication, such as lymphatics or epithelium of intestine to bloodstream
When would passive viremia occur?
day 0
When would primary viremia occur?
day 1-3
When would secondary viremia occur?
day 3-14
Do macrophages always kill viruses?
NO; virions may be phagocytosed and may replicate in macs and came emigrate through walls of small blood vessels as trojan horse
Trojan horse
viruses enter monocyte in lumen of blood vessel and cross blood tissue barrier then leave monocyte in the tissue
3 ways to clear virus from bloodstream
- mononuclear phagocytes in spleen, liver, bone marrow
- antibody clearance
- complement-mediated clearance
neurotropic virus
viruses that infect neural cells by neural or hematogenous spread
neuroinvasive virus
viruses that enter CNS after infection of a peripheral site
neurovirulent virus
viruses that cause disease of nervous tissue, manifested by neuro symptoms and often death
Is neuroinvasiveness and neurovirulence high or low for herpes simplex virus?
neuroinvasiveness: low
neurovirulence: high
Is neuroinvasiveness and neurovirulence high or low for Mumps virus?
neuroinvasiveness: high?
neurovirulence: low
Is neuroinvasiveness and neurovirulence high or low for rabies virus?
high for both!
100% lethality unless antiviral therapy administered shortly after infection
neural spread of viruses
- within axons
- in perineural lymphatics
- in endoneural space
- via infected Schwann cells
retrograde spread
travel opposite direction of nerve impulse flow; invades axon terminals then spreads to dendrite or cell body, then crosses synapse to reach next axon terminal
anterograde spread
travel in direction of nerve impulse flow; virus invades dendrites or cell bodies and spreads to axon terminals, then crosses synaptic contacts to invade next dendrite
centripetal movement
towards CNS
centrifugal movement
from CNS within peripheral nerves to other locations in the body
T/F neural spread of viruses can occur through olfactory routes
T: anterograde up olfactory nerve to CNS (olfactory bulb)
methods to spread viruses through BBB
- increasing permeability of endothelial cells through secretion of TNF
- breakdown of endothelial cell junctions through MMP
- trojan horse (trafficked by monocytes)
Is the incubation period long or short for systemic acute infections ?
long
What is the duration of immunity for localized acute infections?
variable, may be short
lifelong for systemic
T/F secretory IgA is important for localized acute infections?
T : veryyyy
T/F the shedding of infectious virions is crucial to the maintenance of infection in populations
T
How are acute infections shed?
intensive shedding over a short time period
How are persistent infections shed?
shed at lower titers for months to years
tropism
specificity/affinity of a virus for a particular host tissue
pantropic viruses
can replicate in more than one host organ/tissue
rash
general term applied to any temporary eruption on the skin
What disease causes a bulls eye rash?
Lyme disease
vesicle on skin
small distinct elevation with fluid
localized = papilloma
disseminated = lumpy skin disease
ulcer
opening in skin caused by sloughing of necrotic tissue, extending past epidermis
nodule
palpable, solid, elevated mass with distinct borders
*extends deep into dermis = tumor
warts
benign skin growths that appear when a virus infects the top layer of skin
papule
solid elevations without fluid with sharp borders
erythema
reddening of skin, consequence of systemic viral infections (endothelial injury in blood vessels throughout body, including those of subcutaneous tissues)
GI tissue injury
destruction of enterocytes -> malabsorption, diarrhea, dehydration, acidosis, hemoconcentration
viral-bacterial synergism
when the respiratory tract is infected with both virus and bacteria the % mortality is greater than each alone combined
Which virus causes progressive demyelination?
canine distemper
What disease can cause neuronal vacuolation?
Prion disease
Petechiae hemorrhage
pin point /small spots
ecchymoses hemorrhage
larger areas of hemorrhage, ill defined margins
disseminated intravascular coagulation (DIC)
complication arising from viral infections of blood vessels; widespread activation of clotting cascade -> blood clots in small blood vessels throughout body
What happens when clotting proteins in blood are used up in DIC?
severe bleeding can occur from various sites
teratogenesis
abnormal development or arrests in development of embryo or fetus -> death or malformations during antenatal period
What can cause congenital hydraencephaly in calves and how does it present?
BVDV -> recumbence, depression, dome shaped skull
What happens to a non-pregnant animal with BVDV?
usually mild infection, scours, milk drop, reduced WBCs
What happens when a pregnant cow has a transient infection of BVDV?
naturally immune
What occurs when a cow with a 1 month pregnancy has BVDV?
embryo death
What occurs when a cow with 2-4 month pregnancy has BVDV?
persistent infection (PI calves) -> immunotolerant
What occurs when a cow with 5-9 month pregnancy has BVDV?
middle: abortion, deformities
late: normal calves
What is the danger of an immunotolerant calf?
the virus can mutate to become cytopathic and cause a superinfection -> can infect other viremic animals and lead to fatal mucosal disease
virus induced immunopathology
tissue injury mediated by host immune response to virus infection; cause of damage with viruses that are persistent -> chronic immune response
What happens when NO and superoxide are produced in abundance?
cell damage! normally inhibit viral replication
When do antibody mediated inflammatory reactions involve toxicity?
- engagement of IgG with Fc receptors on inflammatory cells which causes inflammatory release
- following deposition of viral antigen-antibody complexes in capillary beds, leading to activation of complement cascade
What causes immune complex-mediated vasculitis and what is a common sign?
feline infectious peritonitis; distended abdomen
What can happen when macrophages release IL10?
skew immune response from TH1 to TH2 -> diminishes cell-mediated immunity
infectious bursal disease
virus replication causes atrophy of bursa and deficiency of B lymphocytes resulting in immunosuppression
inapparent infections
clinical signs and symptoms are not evident; too few cells may be infected
persistent infection
pathogen not cleared efficiently by adaptive immune response -> infectious virus demonstrable continuously whether or not there is ongoing disease
latent infection
infectious virus not demonstrable except when reactivation occurs -> often stimulated by immunosuppression and/or action of cytokine or hormone (ex. cold sores)
chronic infection
virus continuously shed from or is present in infected tissue; sometimes starts as acute infection (ex. foot and mouth disease in cattle)
slow infection
prolonged incubation period, lasting months or years; quantities of infectious virus gradually increase during a very long preclinical phase; slow lethal progressive disease (ex. prions)
