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37 Cards in this Set
- Front
- Back
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What are the 3 common ancestors of viruses and what families of viruses originated from them?
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Mononegales- non-segmented -RNA viruses
Nidovirales- coronaviridae and arteriviridae +RNA have common origins in 3 groups: picorna-like toga-like flavi-like |
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What are the 5 important properties of viruses which can vary.
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Capacity to replicate rapidly
Replication to high titer Entry and invasion of cells and tissues Persistence, latency and/or prolonged shedding The ability to avoid or supress the host responses |
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How does a virus avoid or supress host responses? (name 3 ways)
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suppression of the presentation of viral antigenic peptides
interfering with cytokines and their receptors inluencing the innate responses of the host cells |
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Name the 5 mechanisms of viral variation and evolution.
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Point mutations
Mutation rates and viral variation Recombination and reassortment Host genes picked up by DNA viruses Sequence variation and selection |
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Describe point mutations and give examples.
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Error-prone replication (RNA) gives rise to variant viruses, including strain variation.
Ex. Influenza from low to high pathogenicity virus; canine parvovirus emerging as a variant host range virus |
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Describe mutation rates and viral variation and give examples.
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Error rates may depend on the virus: replication fidelity, tolerance of the virus for change, variation in the selection imposed on the virus, the "population" size of the virus, and recombination or reassortment that occurs.
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Explain recombination and give examples.
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Happens during CO-INFECTION of a cell with TWO VIRUSES; allows mixing of changes in the virus and the generation of new sequence and mutation combinations.
Common among +RNA, retroviruses, and a number of DNA viruses. WEE arose by recombination b/w a virus from EEE/VEE group and a virus that was more like sindbis virus. Some viruses aquire genes from the HOST ex. BVD- cytopathic variants often have host RNA insertions into the NS3 gene that make the protein PRONE TO CLEAVAGE. The virus is then more cytopathic and may be recognized by the host responses. Recombination may occur b/w wild type and vaccine strains of some viruses- the RECOMBINANTS have altered antigenic form and increased virulence compared to the vaccine. (IBV & CALICIVIRUS) |
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Explain reassortment and give example
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generation of new genetic and antigenic combinations
ex. INFLUENZA (orthomyxoviruses); occurs frequently in nature b/w animal influenze viruses to give variants with different properties. |
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How can we detect variation and relationships in viruses?
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ANTIGENIC VARIATION- using polyclonal or monoclonal antibodies (serum neutralization and ELISA assays)
SEQUENCE VARIATION- PCR for DNA viruses, or RT-PCR for RNA viruses. The DNA product is sequenced, which shows exactly which virus is present, and whether it has any variation from the sequences of other viruses. IMPORTANT FOR TRACKING SOURCES OF VIRUSES AS WELL AS THEIR SPREAD...USEFUL FOR VIRUSES WHICH VARY RAPIDLY OVER TIME (RNA VIRUSES) |
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Describe an acute viral infection.
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Rapid production of infectious virions, followed by rapid resolution of the disease and clearing of the virus by the developing adaptive immune responses.
May be very mild, and inapparent (subclinical) infections are common for many viruses and can be a major source of virus spreading in the population. |
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Describe an acute viral infection leading to persistence.
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Virus overcomes the innate immune responses of the host, and causes a normal infection, but the virus is not completely cleared by the host response. Virus may persist at low levels compared to the initial primary infection titers, give a continuing or recurring source of virus for other animals.
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Describe latent viral infections.
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Special case of persistent infection, where the virus persists in a NON-REPLICATING STATE.
HERPESVIRUS, which persists in the ganglia or in lymphoid cells; virus may reactivate if there is a temporary or permanent reduction in the immunity of the host. |
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What are some determinants of a specific virus-host interaction?
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NATURE OF THE Dz:
Target tissue- where the virus enters the body, ability to access the target tissues, viral tropism, permissivity of the cells. Strain of the virus. SEVERITY OF THE Dz: Responses of cells to infection, pre-existing immunity to virus, immune responses, amount of virus inoculated, duration of infection, health of host, nutrition of host, co-infections, host genotype, age of host. |
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What are some determinants of susceptibility that influence viral pathogenesis?
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1. Interactions with target tissues: access to the target tissue, stability of the virus in the body (temp, pH, bile salts), capacity to establish viremia, spread thru the RE system, presence of functional receptors for virus
2. Ability to kill cells (cytopathology): efficiency of virus replication, temp, cell permissivity, cytotoxicity of viral proteins, inhibition of macromolecular synthesis, production of viral proteins and nucleic acids, alterations of cellular metabolism 3. Host responses to infection: innate immune responses, acquired immune responses, viral immune escape mechanisms 4. Immunopathology: Interferon and other cytokines- systemic symptoms, T cell responses- delayed type responses and cytotoxic T cells, Antibody- complement, antibody dependent cellular cytotoxicity, immune complexes. |
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What are some of the routes of viral infection?
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MM- resp, oral, urogenital, conjunctiva
SKIN- breaks, wounds, mechanical (iatrogenic-> needles), invertebrate trans OROPHARYNX and GI TRACT- imp. sites of infection, and resp or fecal shedding is seen for many viruses INTRAMUSCULAR INFECTION- rabies virus infection through bites |
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What are some of the BARRIER to infection?
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SKIN (mechanical)
GI TRACT- low pH of stomach inactivates many viruses, bile salts are detergents that can inactivate (env) viruses, GI proteases in stomach and intestines can inactivate some viruses. RESP. TRACT- Mucus layer, ciliated epithelial cells that clear material deposited, and surveillance of phagocytic cells. (Many resp. viruses can infect and replicate in the epithelial cells, and in some cases in the phagocytic cells) |
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How are viruses disseminated and spread throughout the body?
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LOCAL SPREAD- thru diffustion of released virus, or thru cell-cell fusion that can occur b/w neighboring cells
REMAIN LOCALIZED at SITE OF INOCULATION OTHER SPREAD WIDLEY THROUGHOUT THE BODY causing systemic disease or spread to other tissues (can occur in blood, lymph, nerves) |
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How do viruses spread through LYMPHATICS?
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many spread thru efferent lymphatics to the local lymph node and then through the afferent lymphatics to the thoracic duct then to blood circulation.
Viruses may replicate in lymphoid cells, or be simply transported (may be of free virus or of virus-infected or bound lymphoid cells. |
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How do viruses spread through BLOOD BORNE VIREMIA?
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May be FREE VIRUS or VIRUS infected or assoc with CELLs.
FREE VIRUSES- fairly quickly cleared from the circulation by reticuloendothelial cells, particularly if antibody or complement are bound to the virus. Viremia usually starts a few days after the initiation of the infection, and then terminated (or reduced) by the appearance of neutralizinig antibodies. CELL-ASSOCIATED VIREMIA- virus circulates in monocytes, or B or T cells, or (rarely) in assoc w/ erythrocytes. Infected cells can persist and circulate for long periods and migrate into various tissues. DCs or other APCs can pick up and carry viruses thru tissues. |
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How do viruses get spread through NEURAL SPREAD?
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Viruses spread by entering and trafficking w/in nerves.
RABIES and some HERPESVIRUSES. Viral virulence can determine the ability of different strains to travel through nerves, cross nerve synapse and enter the CNS. MECHANISM of NEURAL SPREAD- active transport (by molecular motors and the cytoskeleton) of the virion or viral components from a nerve terminus to the cell body where the virus can replicate. Some cases virus can later transport back to the nerve terminus to cause a reactivated disease (HERPES) In the case of RABIES- the virus spreads to the salivary glands for shedding. |
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How are viruses shed?
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INTESTINAL SHEDDING- fecal trans of virus
SHEDDING FROM RESP TRACT- sneezing and coughing stim. by virus SKIN- direct virus shedding from undamaged skin, or thru lesions MM AND ORAL AND GENITAL FLUIDS- Rabies shed in saliva, Herpes shed in oral or genital secretions SEMEN- trans by venereal routes or AI MILK- vertical trans. b/w mother and offspring BLOOD- imp for viruses that establish a high level of viremis--> invertebrate trans arboviruses (WNV) URINE- Virurea- virus may replicate in kidney (CAV) or in epithelium of bladder (DISTEMPER) SURVIVAL OF VIRUS AFTER SHEDDING-some are very labile and survive for only MIN. outside the body, others may survive for long periods (weeks-years) under the right circumstances. |
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How is tissue tropism of a virus important in relation to the disease it produces?
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Most viruses have a specific set of tissuse that they infect, and the susecptibility and tissue tropism can depend on the strain of virus being examined.
Cell cycle can also be important when determining SUSCEPTIBILITY to infection, some viruses require a MITOTICALLY ACTIVE CELL for viral replication (PARVOVIRUS); other may require NUCLEAR ENV BREAKDOWN to occur in LATE MITOSIS (simple RETROVIRUSES) ACCESS TO TISSUES- ability of virus to acsess certain tissues may determine the disease that results. CNS- parially protected by "blood brain barrier", however, there are a number of areas where the basement membrane is sparse adn the epithelium is fenestrated (CHOROID PLEXUX). Other viruses may be able to enter the CNS by asc. nerves, which may require that the virus can cross one or more synapses. |
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What are some effects of the virus on the cell?
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Kill the host cell
Rapid Cytopathology in infected cells--> rapid and acute infection Cells may survive for various periods after being infected Infected cells may respond by undergoing APOPTOSIS (many viruses have mechanisms that counteract this host response to keep the cell alive while the virus completes its replication cycle) Host will seek to indentify and lyse infected cells (some viruses have mechanisms that couteract this--> i.e. down regulating expression of CLASS I MHC) DIRECT EFFECT OF VIRUS ON INFECTED CELL: - inhibition of host transcription - inhibition of host translation - interfere w/ host interferon and stress responses, allowing them to replicate - prevent cells from undergoing apoptosis |
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What are 4 direct effects that a VIRUS CAN HAVE ON AN INFECTED CELL?
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- inhibition of host transcription
- inhibition of host translation - interfere w/ host interferon and stress responses, allowing them to replicate - prevent cells from undergoing apoptosis |
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What are some of the systemic effect of CYTOKINES after virus infection (why do many viruses induce "flu-like" symptoms?)
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1. Virus lead to TISSUE DAMAGE
2. IL-1, TNF-alpha, IL-6--> act on hypothalamus to give FEVER and FATIGUE 3. LN swollen through LYMPHOCYTE MOBILIZATION AND PROLIFERATION. 4. release of ACUTE PHASE PROTEINS FROM LIVER (MANNOSE BINDING PROTEIN, FIBRINOGEN, C-REACTIVE PROTEIN, SERUM AMYLOID PROTEIN) 5. CSFs (colony stimulating factors) stim. bone marrow--> HEMATOPOESIS and LYMPHOCYTE MOBILIZATION |
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What are the 4 different classes of viral genes that can INFLUENCE THE VIRULENCE of the INFECTION?
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1. Affect of the virus to replicate in cells
2. Modify or counteract the host defenses 3. Facilitate the virus spread among hosts 4. Directly toxic to cell |
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How does VIRAL VIRULENCE play a role in the DEVELOPING CLINICAL SIGNS OF DISEASE?
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1. Ability to spread into CNS
2. Tropism for particular tissues (can distinguish virulent from a less virulent strain) 3. Proteins that the virus encodes can vary (manipulate host responses or induce tumors) 4. Ability to spread b/w members of same species. Clinical signs that develop after infection are a reflection of the viral replication and direct damage to cells and tissues, host repsonse to virus, and effects of any secondary or dual infections. VIRUS may cause damage thru direct effects on infected cells. HOST RESPONSES may cause greatest role in development of clinical disease (due to T-cell mediated cell destruction, to immune complex formation, or to other effects of the innate or adaptive immune responses. |
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What are some factors that determine HOST SUSCEPTIBILITY?
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IMMUNE STATUS- (MATERNAL IMMUNITY)
PRE-EXISTING IMMUNITY TOLERANCE STRESS PREGNANCY PRESENCE OF OTHER PATHOGENS AGE GENETIC VARIATION IN SUSCEPTIBILITY SEASONALITY OF INFECTION AND DISEASE |
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How does the IMMUNE STATUS effect HOST SUSCEPTIBILITY?
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NEONATAL (or fetal) and OLD ANIMALS--> reduced adaptive and innate immune responses
MATERNAL IMMUNITY- antibody acquired by transplacental transfer or from colostrum--> can protect against infection of neonatal or fetal animal, and when absent infection of neonatal animals can lead to MORE SEVERE DISEASE (or chronic or immunologically tolerant infections) |
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How does PRE-EXISTING IMMUNITY effect HOST SUSCEPTIBILITY?
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- usually reduces severity of susbsequent infection
-RARELY- can cause more Severe disease (due to antibody dependent enhancement of infection, or thru more rapid development of immune pathology.) |
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How does TOLERANCE effect HOST SUSCEPTIBILITY?
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- viruses can establism life-long chronic infections allowing successful maintenance (BVD, lymphocytic choreomeningitiis (LCMV))
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How does STRESS effect HOST SUSCEPTIBILITY?
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- corticosteroid production can lead to temporary REDUCTION IN ACTIVE IMMUNE RESPONSES.
(Shipping fever, or introduction of new animal into new herd or flock) |
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How does PREGNANCY effect HOST SUSCEPTIBILITY?
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- increased susceptibility to infection and disease, likely due to immune modulation that protects the fetus and to hormonal changes.
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How does the PRESENCE of OTHER PATHOGENS effect HOST SUSCEPTIBILITY?
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- primary infection by virus leads to mild disease, but MIXED INFECTION with MORE THAN 1 PATHOGEN lead to more SEVERE DISEASE.
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How does AGE effect HOST SUSCEPTIBILITY?
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-Viruses that require rapidly dividing cells are more likely to cause disease in neonatal or young animals (PARVO).
- Older animals may also be more susceptible due to the "blood-brain-barrier" being LEAKIER, allowing viruses to acsess CNS more readily than in younger animals causing ENCEPHALITIS (DISTEMPER- OLD DOG ENCEPHALITIS) |
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How does GENETIC VARIATION IN SUSCEPTIBILITY effect HOST SUSCEPTIBILITY?
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- many viruses cause a more SEVERE DISEASE in NON-NATURAL Hosts than in their normal hosts
-w/in a single species there may be a variety of SUSCEPTIBILITY GENES -other common factors- INNATE (particularly interferon) RESPONSE, and the CLASS I or CLASS II MHC HAPLOTYPES, which can determine the ability of the host to present Viral antigens to the adaptive immune response. |
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How does SEASONALITY OF INFECTION AND DISEASE effect HOST SUSCEPTIBILITY?
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- many virus infection show a seasonal distribution, with increase in one or another.
- vector borne viruses are spread in summer mothes when inverebrate vectors are widespread (WNV) - others are spread in winter (resp. viruses) which can be due to changes in animal housing (less ventiliation), virus survival in the environment, or intro. of large numbers of new susceptible animals. |
