Exam 1: introduction, pathogenesis, diagnosis, vaccination Flashcards
Viruses acquire new host range via _____________ of viral genes
mutation
infection + disease in new host species -> ________ host range
increased
change in viral ____________ or _________ have the ability to spread efficiently between new individuals
receptor or proteins
infection of new _________ ________
Ex: mutations in feline enteric corona virus -> replication in macrophages -> feline infectious peritonitis
cell types
________ effects upon infected cells Ex: noncytopathic BVDV -> cytopathic BVDV -> mucosal disease
different
____________ viral replication -> ___________ severity of disease
Ex: higher affinity of viral spike to ACE2R in Delta SARs varian
increased viral replication -> increased severity of disease
T/F - Mutation does not always = more severe disease
Ex: Parvovirus 2a vs 2b vs 2
true
responsible for distinct strains of many viruses; used in epidemiological studies to track virus spread / determine host
antigenic drift
knowledge of viral ____________ is required for diagnosis, management, and prevention of viral disease
pathogenesis
in this disease, vaccinated puppies may get the disease, as maternal antibodies interfere with development to the immune response to the vaccine – need to vaccinate every 2 weeks
canine parvovirus
best test to differentiate between FIPV and feline enteric coronavirus
immunocytochemistry
replicate in nucleus of cell
DNA viruses
replicate in cytoplasm of the cell, high rate of mutation
RNA viruses
replicate in nucleus, integrated into host DNA as a provirus
retroviruses
an infectious, obligate intracellular parasites; hijack host cellular processes for replication & synthesis of viral components
virus
vehicles for viral transmission
virions
resistant to drying, heat, action of detergents, acid, and proteases
capsid
___________ transmission vital for long-term survival in the environment, retained infectivity on surfaces
fomite
_________________ viruses released via lysis of infected cell
non-enveloped
component sensitive to heat, drying, detergents, acid; must stay dry to be transmitted to new host via droplets, secretions, feces
envelope
T/F - Viruses with envelope do survive as long as non-enveloped viruses
false
the process by which the envelope is acquired from the host cell membrane - virus therefore does not need to kill cells to spread
budding
nuclear or cytoplasmic aggregates of viral substances, typically capsid protein; represent sites of viral multiplication
Ex: found in bronchiolar epithelial cells w canine distemper virus
inclusion bodies
cell membrane is punctured, made to further connect with the unfolding viral envelope (i.e. herpesvirus, retroviruses, influenza)
cell membrane fusion / hemifusion
host cell takes in viral particle through receptor-mediated endocytosis OR phagocytosis (i.e. parvovirus)
endocytosis
injection of viral genome into host cytoplasm through creation of a pore in host membrane, mediated by pore-forming peptide (i.e. poliovirus)
Pore mediated penetration
study of infection and spread of viruses in the animal, and the mechanism by which disease is produced
pathogenesis
virus capable of inducing disease or lesions
pathogenic
measure of the ability of a virus to produce disease in the host; important in determining outcomes of infection
Ex: modified live virus < wild-type virus
virulence
T/F - Some infectious animals replicate and shed virus without clinical disease
true
sources of viral infections include:
a) infected animals
b) persistently-infected animals
c) animal products
d) environment
e) reservoir hosts
all of the above
most important route of transmission for most viruses – direct contact, indirect contact, or vectors
horizontal
transmission between cohabitating animals (i.e. respiratory aerosol droplets)
direct contact
virus transmitted from parent to offspring (i.e. germplasm, eggs, placenta, milk)
vertical transmission
genetic material of an organism that may be transmitted from one generation to another
germplasm
dependent on titer of virus, distance between animals, air movement, droplet size, immunity to virus
respiratory transmission
Higher the titer = ________ the transmissibility
higher
Smaller distance between animals = ________ transmissibility
higher
Less air flow / ventilation = __________ transmissibility
higher
normal, immune fetus may result if infected in late pregnancy when fetus is immunologically competent
placental transmission
direct cell _________ -> loss of organ function
Ex: canine parvovirus: direct damage of crypt epithelium in SI -> failure to renew enterocytes -> blunting of villi + diarrhea
damage
cell ____________ -> tumor production + loss of organ function
Ex: Bovine leukemia virus lymphosarcoma
transformation
____________ cells which target the virus cause destruction of cells in its vicinity (Ex: Distemper, FIPV)
inflammatory
occurs via destruction of lymphocytes and macrophages
immunosuppression
disease in which antigen/antibody complexes accumulate in the basement membrane of renal glomeruli, arteries, or choroid plexus (Ex: Equine Infectious Anemia)
immune-complex
severity of disease is dictated by (3)
location, function, regeneration
T/F - skin, liver have capacity to regenerate & require extensive damage to cause disease, whereas neurons cannot regenerate and little damage causes severe disease
true
entry, replication, lesions, shedding occur within same organ system (i.e. influenza virus)
localized infection
spread to other systems upon entry, shedding in several secretions and excretions (i.e. distemper)
systemic infection
viral spread via lymphatics to regional lymph nodes
primary amplification
virus enters bloodstream -> _________ ________ -> no clinical signs
primary viremia
dissemination into central organs such as the liver, spleen, bone marrow, and vascular endothelium -> __________ ___________ -> clinical signs such as fever/malaise
secondary viremia
____________ into sites of shedding & primary lesions -> characteristic clinical signs, damage
dissemination
viral ________ and __________ occur before and during fever / clinical signs – take diagnostic samples early, or wait until post-infection
replication and shedding
recovery from viral infections occurs via _____________ of susceptible cell populations
depletion
immune responses occur specifically via ________ and ______________ responses
antibody and cell-mediated cytotoxic
study of frequency and distribution of viral diseases in a population
viral epidemiology
prohibition or restriction on the movement or importation of animals / animal products from areas in which disease occurs (for imports, epidemics, biosecurity)
quarantine
restricts sources of infection by reducing the risk of exposure of domestic animals to reservoir hosts – includes housing livestock, fencing pastures, removal / vaccination of wildlife
wildlife control
intended to reduce the risk of spread of infection by insect vectors – includes insect proofing, insecticides, larvicides, adulticides
vector control
associated with presence/absence of host cell receptors on target cells, transcription factors, DNA replication enzymes, proteases
susceptibility
animals with defects in _________ _________ have higher susceptibility to viral infections
cell-mediated immunity
inhibit viral replication & kill viral-infected cells (3)
interferon, NK cells, macrophages
cell-mediated response occurs within________ , antibody production occurs within __________
10 days, 2 weeks
antibody production / CMI occurs __________ in higher frequencies with vaccine protection
faster
important in preventing initial entry of viruses, decrease initial load of virus in blood
antibodies
important in recovery from established viral infection, preventing further viral replication & clearance from host
cell-mediated immunity
may be related to maturation of immune system or stage of differentiation of target cells
Ex: parvovirus – infects cardiomyocytes in puppies 3w or less
Ex: feline panleukopenia – infects neurons in cerebellum in kittens in-utero up to 4 weeks of age
age
elevated body temp inhibits replication of many viruses, enhances host inflammatory reaction, aiding in viral clearance
fever
surface barriers include (3)
skin, intestinal enzymes, mucus
viruses __________ immune responses via:
a) induction of immunologic tolerance at a young age (i.e. BVDV)
b) infection of cells in immune-privileged sites
c) non-neutralizing antibodies
d) integration of viral genome into host chromosomal DNA
e) infection of lymphocytes & macrophages
f) inhibition of MHC function
avoid
down-regulation of viral protein expression // intracellular localization hides viral proteins
i.e. alpha herpes virus – sensory ganglion neuron latently infected, no viral protein expression
latency
viruses evade T cell-response via infection of cells lacking
MHCI
mutation of viral genes responsible for large number of serologically distinct strains of viruses; subtle changes directed by requirement to retain function & escape detection by existing antibodies
antigenic drift
viral genomic segments combine / reassort, producing highly pathogenic viruses; responsible for most severe influenza epidemics
antigenic shift
occurs when viral antigen persists, continued immune response at the site of viral infection results in extensive damage to surrounding tissue via the bystander effect (i.e. canine distemper, feline infectious peritonitis)
virus induced immune mediated inflammatory disease
antiviral antibody interacts with virus in the fluid phase, resulting in formation of virus-antibody immune complexes continuous trapping within renal glomeruli, arteries, choroid plexus glomerulonephritis, arteritis, choroiditis (i.e. equine infectious anemia)
immune-complex disease
often occurs as some viruses destroy lymphocytes, predisposing the host to develop opportunistic infection (i.e. feline immunodeficiency)
immunosuppression
detection of viral antigens/proteins via
ELISA/immunocytochemistry
detection of viral nucleic acids via
PCR
detection of antibodies to virus via
serology
All are _____________ & will give a negative test if the target virus is not present, even if other viruses are
virus-specific
________ result confirms presence of a specific virus OR antibody to a virus; indicates chronic infection (bovine leukemia) or disease (parvovirus, distemper)
positive
Vaccination w high-titer vaccines -> positive PCR/ELISA test for ____________ with NO wild-type virus or disease (i.e. parvovirus)
7-10 days
___________ antibody result indicative of previous infection, previous vaccination, OR maternally-derived passive antibodies
positive
T/F- Antibody levels highly variable among animals – interpretation can be conclusive from a single sample
false
__________ results - specific virus/antibody NOT detected, indicative of NO infection
Exceptions: wrong timing, wrong choice of sample, wrong individual animal
negative
reasons for testing:
a) diagnosis / management of disease
b) certification of freedom from specific infections
c) disease surveillance
d) monitoring for public-health significance
all of the above
Detection of virus dependent on (3)
site, animal, and time
T/F - Virus replication does always coincides with observed clinical signs
false
T/F =- Multiple samples are vital – for both virus + antibodies
true
______ samples used for virus detection assays (PCR, ELISA)
unfixed
______ samples used for microscopic examination / immunocytochemical assays (viral antigens)
fixed
T/F - Vaccines do not prevent infection – used to prevent and manage viral disease by ‘priming’ the immune system to respond to exposure to the antigen
true
T/F - Exposure to the same antigen results in lower level + more rapid secondary immune response
false
T/F - Vaccine types vary in disease mitigation
true
vaccine types are mostly ___________, EXCEPT for rabies and circovirus (inactivated)
modified-live
herd immunity achieved between __________ vaccination, depending on how contagious the virus
70-90%
antibodies produced following viral infection (3)
IgG, IgA, IgM
for __________ spreading viruses (i.e. distemper) – high IgG titers + cell-mediated immunity are important
systemic
for _________ infection (i.e. influenza) – secretory IgA offers protection
local
Proof of protection is established by challenge of vaccinated animals with ___________ virus
wild-type
If a virus is intracellular or has established a latent infection, ___________ immunity is more important for protecting
cell-mediated
T/F - Serum IgG does not correlate w persistent / latent infections (i.e. retroviruses, alpha herpesviruses)
true
If viremia occurs, serum _______ can bind virus and block entry into cells
IgG
objectives of vaccination:
a) disease prevention
b) mitigation of disease
c) protection of unvaccinated population
all of the above
T/F - One approach to vaccination applies to all viral diseases
false
vaccines that protect from diseases that are endemic to a region, of public health significance, required by law, caused by highly infectious vaccines, those posing a severe risk of disease
i.e. canine parvovirus, distemper, adenovirus 2 – begin as early as 6w of age, at 2w intervals
core vaccines
vaccinated puppies (8w) are protected from exposure to WT virulent parvovirus at
10 weeks
most common cause of vaccine failure is _______ ________ interference
maternal antibody
vaccine designed to immunize against two or more strains of the same microorganism, or two or more microorganisms
Multivalent vaccine
T/F - Level + length of time of protection vary with individual vaccines and individual animals
true
vaccine ______________ is often due to incorrect storage, expiration, or incorrect administration
inactivation
Determination of __________ status is vital for assessment of animals with: unknown vaccination history, overdue vaccinations, those undergoing chemotherapy, immunosuppressive drugs, or history of adverse reactions
antibody
contain agents capable of replicating within the animal, yet have attenuated pathogenicity (non-virulent)
Modified live vaccines
derived from naturally-occurring pathogens, produced by generation of non-virulent virus by attenuation in cell culture
Modified live vaccines
Contain high titers of a low passage strain of the target virus – may produce a higher level immune response, likely to overcome low levels of maternal antibodies
Modified live vaccines
Choice for situation where multiple injections are not feasible, producing a higher level immune response (i.e. shelter animals)
Modified live vaccines
Decreased potential for allergic reactions
Modified live vaccines
Highly susceptible to inactivation – proper handling & storage is critical
Modified live vaccines
May acquire mutations in host & revert to virulence – rare, but requires monitoring
Modified live vaccines
stimulate a broad range of immune responses & long-lasting duration of immunity with administration of fewer dose; however, poses greater risk to animals
Live vaccines
engineered by incorporation of genes for a pathogen’s antigen proteins into a harmless carrier virus
Recombinant vector vaccines
Cannot induce a robust immune response in the host or revert to virulence or cause disease
Recombinant vector vaccines
deletion or inactivation of a virus gene that is required for virulence, while leaving the capability of virus to replicate intact (aka DIVA – differentiating infected from vaccinated animals)
Deletion vaccines
may be non-amplifying or self amplifying – lead to efficient generation of antigen-specific immune responses to inserted genes of target viruses
Ex) Venezuelan equine encephalitis virus – used as potential vaccine delivery platform
Ex) Alphavirus replicons – have structural proteins deleted, and replicate vector RANA in cytoplasm
RNA vaccines
RNA viruses target specific pathogens to produce prescription, and may include __________ vaccines against viral and bacterial pathogens
customized
non-infectious, no reversion to virulence, no shedding of virus after immunization; usually require a higher antigen mass, adjuvant, multiple doses, and frequent boosters
Inactivated vaccines
Stable in storage
Inactivated vaccines
Safe for pregnant and immune-suppressed animals
Inactivated vaccines
Require adjuvants
Inactivated vaccines
likely to induce hypersensitivity reactions, injection site-reactions (granulomas/abscesses). & sarcomas in cats (associated with adjuvants)
Inactivated vaccines
contain a portion of the organism – specific purified proteins that are not infectious
Subunit vaccines
DNA coding for antigenic proteins of a viral pathogen is directly injected into animals
DNA vaccines
any undesirable side-effect or unintended effect including the apparent failure to protect from the disease
adverse events
________ reactions (more common): pain, pruritis, alopecia, transient lameness
local
T/F - Reversion to virulence (i.e. MLV vaccines) is common with commercial vaccines for most viral pathogens
false
antiretroviral drugs that inhibit reverse transcriptase & nucleic acid synthesis
retrovir
inhibits viral DNA polymerase preventing further viral DNA synthesis
acyclovir
