Vet Virology Exam 2

Front 1

what is the 'hallmark' characteristic of herpesviruses

Back 1

the ability to achieve latency
– may be silent for months, years followed by reactivation – recrudescence.

Front 2

how do alpha, beta, and gammaherpesvirinae differ

Back 2

Alphaherpesviruses grow rapidly, lyse cells and achieve latency in neural ganglia.


Betaherpesviruses are the cytomegaloviruses; replicate slowly, cell lysis later, achieve latency in secretory glands, lymphoid tissue, and other tissues.


Gammaherpesviruses are lymphotropic; may be cytocidal in epithelial tissue; latency in lymphocytes; associated with oncogenesis.

Front 3

gammaherpesvirinae attack what cell type?

Back 3

lymphocytes

Front 4

Betaherpesvirinae acheive latency where?

Back 4

secretory glands

lymphoid tissue

other tissues

Front 5

Alphaherpesvirinae achieve latency where

Back 5

in neural ganglia

Front 6

Are herpesviruses associated with oncogenesis?

Back 6

yes (gammaherpesvirinae)

Front 7

herpesvirus

viral properties

Back 7

Icosahedral capsid.
- 162 capsomers, hollow.
- 100-200nm

Tegument around capsid
- Fibrous, amorphous.
- Contains viral enzymes involved in replication.

Envelope around tegument –
- Diameter ~120-300nm.
- Derived from nuclear membrane.

Core of linear dsDNA.
- 120-230kbp
- Repeat sequences at termini

Capsid proteins – hollow.

8-12 envelope glycoproteins.
- Designated gA, gB, gC…….
- Function in attachment, fusion of envelope with cell membrane, penetration.
- One binds Fc of IgG.

Proteins involved in regulation and replication.

Proteins involved in growth regulation and immunomodulation.

Proteins also found in tegument.
- alpha-TIF is an important activator of transcription
- VHS – shuts down host protein synthesis

Front 8

know the appearance of the herpes capsid

Back 8

Front 9

know the appearance of herpesviruses

Front 10

know the appearance of herpesviruses

Front 11

Back 11

herpesvirus

Front 12

Back 12

herpesvirus

Front 13

herpesvirus genome

Back 13

Inverted repeat sequences flank the genome.


Genes divided into 3 classes.

alpha - immediate early
- Regulatory proteins
- Not packaged in virion

beta - early
- Replication enzymes incl

DNA polymerase
gamma - late
- Structural proteins

Front 14

what is the purpose of the inverted repeat sequences associated with herpesvirus genome

Back 14

Allow linear double stranded genome to fold back on itself

Repeat sequences sprinkled throughout the genome to help it fold up in different ways

Front 15

Herpesvirus attachment is mediated by ________

Fusion is mediated by ________

Back 15

Attachment is always mediated by envelope glycoproteins.


Fusion is mediated by other peplomeres

Front 16

In herpesviruses _______ is like the mafia going in and taking out the competition

Back 16

viral host shutoff protein

Front 17

Herpesvirus

______ is important in starting the whole transcription process

Back 17

alpha TIF (trans-inducing factor)

Without it, transcription (1st step after uncoating) can’t happen

Front 18

herpesvirus replication - Complex

Back 18

Attachment via viral envelope glycoproteins.
- Interacts with cell surface proteins, e.g. nerve growth factor receptors, TNF receptor.

Fusion of envelope with cell membrane mediated by viral glycoproteins.

Viral Host Shutoff (VHS) protein released from tegument; degrades host mRNA.


Viral capsid with tegument proteins migrates to nuclear pore.

Viral DNA “injected” into the nucleus, along with few viral proteins.
- α TIF (trans-inducing factor)
- Activates transcription of early proteins

DNA replicated by rolling circle mechanism

gamma genes activated.
- Structural proteins made.
- Include capsomers, envelope glycoproteins, and tegument.
αTIF and VHS.

Capsid is assembled in the nucleus.

DNA genome packaged in preformed capsids by viral protein.
- This protein also cleaves the concatemers.

Capsid buds through the nuclear membrane, ER or plasma membrane.

Front 19

describe herpesvirus transcription

Back 19

Transcription uses cellular RNA polymerase; viral proteins are also involved.


Early transcription divided into immediate and delayed phases.

Products of immediate early (α) migrate back to the nucleus.

Activate subsequent transcription; α4 important transcription activator – activate delayed early genes (β).

Delayed early products mediate DNA replication.
- Includes viral DNA polymerase.
- Accumulation of these proteins leads to DNA replication.

Front 20

understand herpesvirus feedback system

Back 20

Front 21

describe herpesvirus binding through penetration in general terms

Back 21

Binding via envelope glycoproteins

Fusion via viral glycoproteins

Migrates to nucleus

Dumps genome and a few proteins into the nucleus

Front 22

understand how herpesvirus gets into the cell -> uncoating

Back 22

Front 23

how does herpesvirus replication occur?

Back 23

DNA is replicated by a rolling circle mechanism.
- Thymidine kinase – viral enzyme provides DNA precursors in nondividing cells, such as neurons.
- Concatemers formed (multiple copies of the genome)



This isn’t a circular genome (it’s linear) but it can circularize (due to repeat sequences) which helps make replication more efficient

Front 24

How does a herpesvirus get its envelope?

Back 24

its envelope can come from different regions (golgi, nuclear membrane, ER, etc)

It can potentially bud through many membranes to get the envelope (not successive, it gets the envelope then loses it before it buds through the next membrane)

Front 25

herpesvirus

cellular effects

Back 25

Chromatin displaced, framework used by virus.

Cell membrane altered.
- Env GP inserted, target for immune response.

Intranuclear inclusions characteristic.

Shut-down of cell metabolism.
- DNA, RNA, protein synthesis, glycosylation all affected.
- Leads to cell lysis.

Front 26

how are viral actions detrimental to the cell

Back 26

Takes over synthetic machinery

Uses up the building blocks of DNA

Envelope glycoproteins inserted into membrane in preparation for budding make the cell a target

lytic infection

Front 27

describe herpesvirus latency

Back 27

Virus enters nerve endings at site of replication, migrates to sensory ganglion.

Genome is maintained intact.

Three phases:
- Establishment
- Maintenance
- Reactivation

Neuron infected acutely; most resolve; a few neurons remain infected with the herpesvirus genome episomal in the nucleus.

Only 1 mRNA produced.
- Latency associated transcript (LAT)
- Unknown if protein produced from it; role unknown.

Passively maintained – proteins of productive infection not produced.

Front 28

how does herpesvirus recrudescence occur

Back 28

Reactivation (recrudescence) leads to productive viral replication at the initial site of infection.

Triggered by stress, other signals (immunosuppression) that lead to transcription in the neuron.

Neuron must survive – how?
- May be that only a few virions are made.
- Viral proteins may inhibit death of the neuron.

Front 29

Herpesvirus

(viral integration during latency/ reactivation/ symptoms during recrudescence/ antibody production during latency)

Back 29

Viral integration during latency
- Episomal: Doesn’t integrate into the DNA, it just sits there until something triggers reactivation

Reactivation
- Forms a virus and moves down axon to replicate in the epithelial cells

During recrudescent episodes, there may be no symptoms
- So this time is a big concern

No antibodies produced/ etc. while in latency

Front 30

common characteristics of herpesvirinae

Back 30

Transmitted by close contact or droplet infection.

Persistent infection with intermittent shedding occurs in all; reactivation is associated with stress, and is usually subclinical.

Alphaherpesviruses produce localized lesions in skin/mucosa; infection with many become generalized including to the fetus.
- many are abortive

Beta- and Gammaherpesviruses are not highly lytic; infections are chronic.

Front 31

1. _____ herpesviruses can be abortive

2. ______ herpesviruses are highly lytic

3. _______ herpesviruses are associated with oncogenesis

4. _______ herpesviruses achieve latency in lymphoid tissue.

5. ________ herpesviruses achieve latency in lymphocytes.

Back 31

1. alpha

2. alpha

3. gamma

4. beta

5. gamma

Front 32

1. ______ herpesviruses replicate slowly

2. _______ herpesviruses grow rapidly.

3. _______ herpesviruses achieve latency in neural ganglia

4. ______ herpesviruses achieve latency in lymphocytes

5. ________ herpesviruses achieve latency in secretory glands.

6. _________ herpesviruses may be cytocidal in epithelial tissue

Back 32

1. beta

2. alpha

3. alpha

4. gamma

5. beta

6. gamma

Front 33

which herpesvirus is lymphotropic

Back 33

gamma

Front 34

vetinary pathogens (herpesvirus)

Back 34

Bovine – abortion, encephalitis, respiratory disease.

Equine – abortion, neurologic disease, respiratory disease.

Swine – neurologic, reproductive and respiratory disease.

Canine – “kennel cough”, neonatal death.

Feline – respiratory disease.

Wildlife species
- Primates – Herpes simiae or Cercopithecine herpesvirus-1 of macaques is lethal to humans (“monkey B virus”).
- Birds
- Marine mammals
- Elephants, Asian and African.
- Probably occurs in most species.

Front 35

Bovine Herpesvirus-1

Back 35

Alphaherpesvirinae

Infectious bovine rhinotracheitis (IBR).

Respiratory disease, vulvovaginitis and balanoposthitis, conjunctivitis, abortion, enteritis, encephalitis (rarely).

Aerosol, sexual, in utero transmission.

Replicates in epithelial cells where entry occurs; also white blood cells - cell-associated viremia.
- Like cooler temps so stay near resp tract but can spread systemic by hitching ride on WBC

Balanoposthitis/Vulvovaginitis
- Genital lesions (esp in dairy cattle)

Respiratory disease with fever, nasal discharge, conjunctivitis; hyperemic mucosa (“rednose”), oral ulcers; predisposes to secondary bacterial infection of LRT.

Diarrhea in neonatal calves.

Abortion in pregnant cows several months after acute infection.

Front 36

BHV-2

Back 36

Alpha

Bovine mammilitis – skin lesions on teats; “pseudocowpox”.

Pseudolumpyskin disease – generalized skin nodules; resembles more serious poxvirus.
- Most common in southern Africa.
- Mechanical transmission by insects.

Front 37

BHV - 3, 4, & 5

Back 37

BHV-5 – Alpha
- Encephalitis
- Neural spread from nasal and oral cavities.

BHV-3 and 4 – Gamma
- Little clinical significance

Front 38

Alcelaphine Herpesvirus-1 & Ovine herpesvirus-2

Back 38

Alcelaphine Herpesvirus-1 (wildebeest); Ovine herpesvirus-2 (sheep worldwide).

Malignant catarrhal fever.

Fatal lympho-proliferative disease of cattle and some wild ruminants incl white tailed deer and bison.

Affects lymphoid and epithelial tissue of respiratory, GI tracts, urinary tracts; vasculitis.

Wildebeests are reservoirs in Africa; Sheep are thought to be reservoirs outside Africa.
- Adapted hosts are asymptomatic
- Disease in nonadapted hosts.

Fever, depression, leukopenia, oculo/nasal discharge, extensive GI mucosal erosions, lymphadenopathy, CNS infection, corneal opacity.

Front 39

mad itch of swine is assoc with which virus

Back 39

pseudorabies (alphaherpesvirus)

Front 40

pseudorabies

Back 40

Pseudorabies – Alphaherpesvirus

Swine are the reservoir, incl feral swine.

Significant economically - USDA eradication efforts ongoing.

Oral/intranasal exposure; neural and viremic spread; shed in saliva and respiratory secretions.

Abortion/stillbirth/weak piglets in pregnant sows.

Mortality in neonates.

Respiratory disease in growing and mature swine with fever, depression, cough; in younger swine progresses to neurologic disease ending in death.

In secondary hosts (cattle, dogs, cats, horses, sheep, wildlife), CNS involvement; aka “mad itch”; ends in death.

Vaccination in endemic areas.

Front 41

what are the 2 porcine herpesviruses

Back 41

pseudorabies (alpha)

Porcine cytomegalovirus (Beta)
- Rhinitis in piglets – leads to weight loss and death.
- May cause fetal death.
- This one isn’t a biggie

Front 42

alphaherpesvirinae tend to attack what 4 tissue types

Back 42

Epithelial cells

Resp tract

Fetus

Occ brain

Front 43

EHV 1&4

Back 43

Alpha

Antigenically related.

Respiratory transmission; viremia occurs.

Rhinopneumonitis – with fever, nasal discharge; pneumonia in foals.

Abortion in pregnant mares usually associated with EHV-1.

Neural disease also associated with EHV-1 due to vasculitis.

MLV and killed vaccines

Can infect camelids

Front 44

EHV 2,3,&5

Back 44

Equine Herpesvirus-3 – Alpha
- Equine coital exanthema
- Pustular genital lesions
- Mild disease


Equine Herpesviruses-2 and -
5 – Gamma
- Questionable significance

Front 45

most herpesviruses target what tissue type?

why?

Back 45

Most target resp epithelium


Like cooler temps
- Impacts cellular tropism
- Don’t usually spread systemically
- Pneumonia rare, repro probs rare

Front 46

_____ is the only feline URT infection that affects the cornea.

Back 46

feline herpesvirus-1 (alpha)

Front 47

feline herpesvirus-1

Back 47

alpha

rhinotracheitis/ also affects cornea

Respiratory spread

Targets epithelia of URT; prefers temp of 33-35C;

Most severe in kittens.

Sneezing, oculo/nasal discharge, salivation, anorexia; may have corneal lesions (keratitis).

Very contagious; problem in shelters, catteries.

Killed and MLV vaccines.
- IgA and cell mediated immunity impt

Front 48

Canine Herpesvirus 1

Back 48

Alpha

Mainly reproductive

Danger time
- Last 3 weeks of gestation and 1st 3 weeks of life

Very little prob in adults

Likes cool temps
- Neonates have probs with regulating temp so can spread systemically in them


Respiratory and genital spread.

Prefers temp of 33-35C; pups have poor temp control.

Associated with kennel cough in adults.

Abortion, neonatal death most serious consequences.

Pups infected in utero or oronasal.

Cell-associated viremia

Replicates in blood vessel walls.

Front 49

Avian Herpesvirus

Infectious Laryngotracheitis

Back 49

Alpha

hemorrhagic tracheitis

potl for secondary pneumonia

Gallid Herpesvirus-1

Transmitted by droplet inhalation.

Necrosis and ulceration of URT; leads to asphyxia.

Cough, sneezing, discharge, gasping, dyspnea.

Mortality may be 50% or higher.

Also associated with lower egg production.

Vaccination in breeding flocks.

Front 50

Marek's Dz

Back 50

alphaherpesvirus

Gallid Herpesvirus-2

Very important disease of poultry.

Virus is shed in dander; inhaled.

Replicates in respiratory epithelia followed by cell-associated viremia (macrophages).

Targets lymphoid tissue; may lead to lymphocyte transformation (oncogenesis); these may infiltrate nerves.

Asymmetric paralysis
“grey eye” – infiltration of iris with neoplastic cells

Skin nodules

Healthy carriers occur.

Vaccination in ovo

Front 51

duck plague

Back 51

herpesvirus unassigned to subfamily/ genus

Anatid Herpesvirus 1

Domestic and wild ducks, geese, other waterfowl.

Ingested; leads to enteritis.

Viremia occurs with vasculitis; hemorrhages occur.

Depression, ruffled feathers, tremors, diarrhea.

Morbidity and mortality can be high as 100%.

Front 52

Psittacine herpesvirus

Back 52

Wide variety of psittacines.

Pacheco’s disease.

Shed in feces, nasal discharge.

Liver is a major target.

Lethargy, ruffled feathers, diarrhea, conjunctivitis, tremors.

Significant mortality

Vaccine available

Front 53

Primate Herpesviruses

Back 53

B Virus of Macaques
- Cercopithecine Herpesvirus 1
- Transmitted through saliva.
- Disease resembles HSV in humans.
- Can be transmitted to humans via bite or scratch, or saliva contact with mucous membrane.
- Ascending paralysis, encephalitis and death.
- High mortality rate; survivors may have permanent impairment.
- Assume all macaques are infected and treat accordingly in terms of safety issues.


Simian Varicella
- Cercopithecine Herpesviruses 6,7 and 9
- Old World monkeys.
- Chickenpox-like signs

Front 54

fish herpesvirus

Back 54

it is a significant pathogen with a high mortality

Front 55

elephant herpesvirus

Back 55

Lethal dz in captive elephants

Carditis and death in young elephants (high mortality)

Originally in asian elephants (we thought)

Turns out it was really from african elephants but they didn't have a problem with it

Front 56

herpesvirus epidemiology

Back 56

Bovine – significant in feedlots, during shipping.

Porcine – Rodents important in PRV spread; significant outbreaks occur when weaned swine from several sources brought together.

Others – situations of crowding, increased density predispose to spread.

Front 57

herpesvirus diagnosis

Back 57

Virus isolation

Virus detection
- immunofluorescence

Serology
- Many animals are seropositive.
- Rising titer or IgM indicates primary infection.

Front 58

herpesvirus tx and control

Back 58

Several antiviral drugs available for herpesvirus infections.
- Most are nucleoside analogs.
- Activated in infected cells, lead to termination of DNA chain elongation.

Vaccine available for many herpesviruses of domestic species.
- BHV 1 - EHV 1 and 4
- PRV - FHV 1
- GHV 1 and 2, AHV 1
- Channel catfish virus

Eradication
- BHV-1 in some European countries
- Pseudorabies

Front 59

how do antivirals help tx herpesvirus

Back 59

adds a fake base

When that fake base is added, it ends the viruses ability to cause dz

Only activated in infected cells

Has a preference for polymerase of herpesvirus

Front 60

_______ is the largest animal virus

Back 60

poxviridae

Front 61

describe the morphology of poxviruses

Back 61

Complex morphology

Dumbell-shaped core
- Contains nucleic acid

Two lateral bodies
- Function unknown

Pallisade layer – tubular to globular proteins.

Lipoprotein membrane – core envelope (intracellular).

Outer envelope derived from Golgi (extracellular).

Loss of outer envelope does NOT remove infectivity.

Front 62

describe the poxvirus genome

Back 62

dsDNA, 130-375 kbp (BIG!!); High A/T content

150-200 genes
- Enzymes for replication.
- Proteins that affect host immune response.

Terminal hairpin loop - denature→ circle

Inverted terminal repeats - Tandem repeats within these regions.

Central region
- Highly conserved
- Genes for replication

Front 63

describe the ends of the poxvirus genome

Back 63

Covalently linked at end
- If you denature it, it will circularize



Ends are non-coding regions
- Repeat sequences
- Fxn in replication and some other regulatory capacity
- Don’t encode proteins but they are impt

Front 64

why is poxviridae different than other viruses we have studied prior?

Back 64

Everything is occurring in the cytoplasm

This is the 1st one that does this
- Can’t utilize the cell enzymes
- No splicing

Everything is done with viral enzymes (still uses ribosomes)

Front 65

what are some properties of poxviruses

Back 65

Fairly resistant


All vertebrate poxviruses share at least one antigen.
- More extensive cross-reactivity within a genus.
- Allows immunization with one species of virus within a genus to protect against another within the same genus.

Front 66

Poxviridae replication

Back 66

Replicates entirely in cytoplasm.
- Steps occur in discrete areas
- Viral factories - inclusions.

Entry by fusion; may follow endocytosis.

Core released.

Virus encodes all the enzymes it needs for replication, incl DNA polymerase and RNA transcriptase.

Early transcription commences upon entry.
- Virus carries RNA polymerase as well as capping and poly A polymerase in mature virion.
- Early transcription factor also carried in which insures early genes are transcribed first.
- Early mRNA made from ~1/2 of genome.
- No splicing (as virus rep in cytoplasm).
- Products are primarily enzymes for DNA replication.

DNA replicaton occurs a few hours after entry.
- Mechanism not well-understood.
- Several enzymes involved.
- Generates concatemers.
- Recombination may occur with other co-infecting poxviruses.
- With replication of DNA, transcription shifts to intermediate and late genes.

Product of early genes allows a shift to intermediate; one intermediate product is late transcription factors.

Products of late transcription are mainly structural proteins.

Some proteins packaged are transcription enzymes to be carried into next host cell.

Virus assembles.
Occurs in discrete sites – seen as inclusions.
- Complex, requiring several hours.

Release by budding through the golgi membrane (EEV) or through cell lysis (INV).

Front 67

what are the products of early, intermediate, and late transcription?

Back 67

Early transcription
- Proteins not carried in that are needed for replication

Intermediate and late
- Structural proteins

Front 68

what are the steps involved in poxviridae infection?

Back 68

1. Entry

2. Early transcription

3. Early translation

4. Modification of host response

5. Release of core

6. DNA replication

7. Separation of concatemers

8. Intermediate transcription

9. Intermediate translation

10. Late transcription

11. Late translation

12. Protein insertion in membrane

13. Assembly

14. “Wrapping” of core with cytoplasmic membrane

15. Release by lysis – lacks outer envelope

16. Budding – acquires outer envelope – virus now in Golgi.

17. Release by exocytosis

18. Cell-to-cell spread

Front 69

Poxvirus pathogenesis

Back 69

Systemic or localized infection depending upon the virus.

Route of entry may be through abrasions or via respiratory tract (smallpox); some transmitted by arthropods.

Replicates at site of entry in macrophages – may remain at site of entry.

May enter lymphatics, and from there spread to bloodstream – systemic spread.

Depending upon immune response and virulence, may see complications, such as toxemia, and death.

Front 70

poxvirus cytopathic changes


(how does it cause cell death)

Back 70

Cause cell death via a number of mechanisms.

Inhibit cell’s DNA, RNA and protein synthesis.
- Via virus protein
- Inhibition of initiation of cellular translation.
- Viral messages > cell messages.
- Host mRNA synthesis and transport inhibited.
- Decreased half life of cell mRNA

Alter membrane permeability.

Uses up cell machinery

Front 71

how do some poxvirus viral proteins affect the host response

Back 71

Defense against host response.
- IFN resistance
- Block of complement cascade.
- Modulation of inflammatory response.


Some have growth promoting activity.
- Viral Growth Factor
- Binds Epidermal GF receptor to stimulate cell growth.
- Increases viral yield

Front 72

orthopoxvirus

Back 72

Smallpox (variola)
- Variola major mortality of ~25-35%.
- Variola minor mortality of ~1%

Vaccinia – vaccine virus.

Monkey pox – rare zoonosis of Africa; can be fatal.

Ectromelia – mouse pox

Cowpox – rodent reservoir; also zoonotic.

Others
- Camelpox, buffalopox, raccoonpox….

Front 73

_______ is the first disease against which a vaccine was developed

Back 73

smallpox

Front 74

______ was the first dz eradicated

Back 74

smallpox

Front 75

smallpox

Back 75

Spread via respiratory tract (inhalation/ ingestion).

Spreads to regional lymph nodes then bloodstream.

Enters epidermis causing necrosis evidenced as vesicles.
- Similar lesion occur in internal organs.

Front 76

what was smallpox eradicable

Back 76

Good cross-protection using vaccinia.

Stable vaccine.

Easy to administer.

No animal reservoir.

No persistent/latent infection.

Long-lasting immunity

Front 77

______ was the 1st virus grown in tissue culture

Back 77

vaccinia

Front 78

vaccinia

Back 78

Descendant of cowpox or variola - unknown.
- Wide host range.
- Induces good long-lasting immunity

The vaccine is contraindicated in people who have or are:
- Eczema, atopic dermatitis or other acute, chronic, or exfoliative skin conditions
- Diseases or treatments which cause immunodeficiency or immunosuppression
- Moderate or severe acute illnesses
- Previous allergic reaction to smallpox vaccine or any of the vaccine components
- Pregnancy
- Breastfeeding mothers
- Infants and children under 12 months of age

Front 79

orthopoxviruses

monkeypox

Back 79

Monkeypox - systemic

Acquired from infected primates.

West and central Africa

Zoonotic - Lab and zoo workers

Similar to smallpox

Pustular rash, fever, toxemia.

Squirrel/rodent reservoir

Front 80

a lot of pox viruses have _____ hosts (doesn't cause dz in them)

Back 80

rodent

Front 81

cowpox

Back 81

Cow is incidental host; host is rodents.

Localized infection in teats, udder; spread by milking.

Also infects cats, humans, zoo animals (esp felids).
- Serious in cats.

May develop widespread skin lesions.
- Secondary bacterial infection may occur.

High mortality in cheetahs.

Found in Europe, Russia

Front 82

Ectromelia

Back 82

Problem in research labs.

Occurs worldwide due to inadvertent spread in lab mice and products.

Infection through abrasions – systemic spread.

May be rapidly fatal.
- Necrosis of liver, spleen.
- Death within hours.

Chronic form exists.
- Ulcerating lesions on feet, tail, snout.

Front 83

camelpox & buffalopox

Back 83

Camelpox
- Severe generalized disease.
- Important in Africa, Middle East, SW Asia
- Case fatality rate may be 25%.


Buffalopox
- Similar to vaccinia.
- Water buffalo in Egypt, Indian subcontinent, Indonesia.
- Pustular lesions on teats and udder; occasional generalized disease in calves.

Front 84

parapoxviruses

Back 84

Cause localized lesions.

Can be economically significant.

Zoonotic – papular lesions.

Front 85

Orf

Back 85

Parapoxvirus

sheep, goats

Contagious pustular dermatitis.
lesions primarily in mouth, muzzle, lips.

May prevent lambs from nursing – economically significant.

Spread by direct contact, fomites.

Vaccine available – ewes near lambing.

Orf is zoonotic
- It’s not forever but it’s not fun

Front 86

parapoxviruses

pseudocowpox/ papular stomatitis

Back 86

Pseudocowpox
- Common in cattle worldwide.
- Lesions on teats, muzzle.

Papular stomatitis
- Worldwide in cattle.
- Lesions on muzzle, lips.

Front 87

Capripoxviruses

Back 87

Lumpy skin disease.

Cattle – Bos taurus, and Bos indicus.

Africa – spread throughout continent.

Fever, nodular lesions in skin, viscera – systemic disease.

Nasal and ocular discharge, anorexia; ulcerated skin lesions.

High morbidity, mortality usually low.

Prolonged convalescence.

Transmitted by insects.

Wildlife reservoir.

Economically significant –
decreased productivity, damage to hides

Controlled by vaccination where endemic.

Fever, nasal discharge, anorexia – systemic dz.

Cutaneous nodules develop; become secondarily infected.
Visceral lesions, incl. lung.

Spread by insects, fomites, respiratory droplets.

Front 88

systemic poxviruses

(suipox/leporipox)

Back 88

Suipox
- Swinepox;
- Mild disease, skin lesions.
- Seen sporadically worldwide.
- Transmitted by biting louse.

Leporipox
- Myxoma – rabbits;
- High mortality in European rabbits with generalized disease.
- Localized benign fibroma in rabbits of Americas.
- Transmitted via insects.
- Shope fibroma.
- Squirrel fibroma.
- Hare fibroma.

Front 89

Avipox

Back 89

Fowlpox – poultry.

Chickens, turkeys.

Vaccines available.

Spread by biting insects.
- Papules on comb, wattle, around beak.
- Lesions may occur on legs, feet.
- Heal in 2-3 weeks.

Droplet infection may occur.
- Mucous membranes of oral cavity, pharynx, trachea.
- Lesions coalesce – can asphyxiate.
- Poor prognosis.

Front 90

most avian poxviruses are seen where?

Back 90

Usually see on feet

Hard to perch (big prob in passerines)

Can make difficult to eat

Front 91

dx of poxviruses

Back 91

Classic lesions

Histopathology - inclusions

Virus detection
- Virus isolation
- Electronmicroscopy
- Polymerase chain reaction (PCR)

Serology

Front 92

poxviridae tx and control.

Back 92

Immunoglobulin

Supportive

Recovery leads to life-long immunity.

Vaccine
- Veterinary vaccines in use for many poxviruses.
- Smallpox vaccination is beginning to be implemented again due to concern over bioterrorism.
- Primarily in “front line” individuals – health care workers, military, law enforcement.

Front 93

poxviruses as vectors

Back 93

Promotes recombination

Live vaccine
- b/c virus producing protein, get presentation in MHC1

Front 94

_____ is an impt virus in commercial fish production

Back 94

iridovirus

Front 95

african swine fever is what kind of virus?

Back 95

asfarvirsu

Front 96

asfarviridae/ iridoviridae properties

Back 96

Asfarviruses
- enveloped, 175-215nm in diameter.
- Complex icosahedral capsid.
- Genome of linear dsDNA 170-190kbp.
- Covalently closed ends.
- Inverted terminal repeats.
- Encodes up to 200 proteins.

Iridoviruses
- Morphologically similar to asfarviruses.
- Enveloped, 160-200nm.
- Icosahedral capsid.
- Genome 95-190kbp.

Front 97

where to asfar/iridoviridae replicate?

what is required for their replication?

Back 97

Will not replicate in anucleate cells

Asfar
- Replicates in cytoplasm, but needs a nucleus for some unknown reason

Irido requires a nucleus (b/c uses cellular transcriptase)
- Transcription occurs in nucleus
- Replication/ assembly in cytoplasm

Front 98

describe asfarvirus replication

Back 98

Replication occurs primarily in the cytoplasm.

Nucleus is needed for DNA synthesis.

Virus provides enzymes for transcription and replication.

After entry, virus uncoats, begins transcription with viral enzyme.

DNA replication similar to poxviruses, producing concatemers.

Front 99

how does iridovirus replication differ from asfarvirus

Back 99

Use cellular RNA polymerase for transcription modified by viral proteins to favor viral mRNA synthesis.


Initial replication is in nucleus; later in cytoplasm.

Front 100

African Swine Fever

Back 100

Asfarvirus

ticks are reservoir
- pigs are accidental host (so they get sick)

Infects domestic swine, and other suids.

Infection may be acquired via the respiratory tract, direct contact, or via tick bite.
- Transtadial, transovarial transmission in ticks.
- Pigs accidental host.

Replicates in leukocytes, first locally in lymphoid tissue, then disseminates via the blood.
- Initially, monocytes and macrophages.
- Leukopenia results.
- Also severe thrombocytopenia.
- Virus inhibits secretion and synthesis of antiviral and proinflammatory cytokines in infected macrophages.
- Virus disseminates widely to RES
- widespread hemorrhages

Many tissues infected.

Swine that survive remain persistently infected.

Virus is shed in all secretions/excretions.

Neutralizing antibodies not produced.
- Unknown why.
- Obstruction to vaccine development.

After incubation of 1-2 weeks, swine develop high fever.

After onset of the fever, the animals stop eating and develop diarrhea, incoordination, and prostration.

Some develop dyspnea, reddening or cyanosis of the ears, and hemorrhages.

Mortality may be 100%.

Adult warthogs do not develop any signs of disease.
- Able to replicate

Front 101

how do you dx african swine fever

Back 101

Signs and lesions.
- Febrile disease associated with hemorrhage and death.
- Important to distinguish from hog cholera.

Virus isolation and antigen detection on tissue and blood.
- Immunofluorescence most common.
- Notifiable!

Front 102

epidemiology of african swine fever

Back 102

(asfarvirus)

Sylvatic cycle in warthogs in Africa.
- Asymptomatic infection in wild pigs; develop viremia.
- Argasid ticks which live in pig burrows are biologic vectors.

Epidemic/endemic cycles in domestic swine.
- Outbreaks in domestic swine can be via ticks or consumption of contaminated food (e.g. uncooked meat from infected swine).
- Ticks in other regions of the world can transmit if virus enters the region.
- After introduction, disease spreads by aerosol primarily; also indirect spread.

Currently endemic only in sub-Saharan Africa and Sardinia.

Front 103

why is african swine fever a serious threat to swine industries throughout the world

Back 103

No vaccine.

Transmission in meat products.

Persistent infections.

Tick vectors.

Front 104

what virus is associated with mass die-offs in frogs?

Back 104

ranavirus (iridoviridae)

Front 105

_______ is second only to parvo in terms of hardiness in the environment

Back 105

caliciviridae

Front 106

Caliciviridae classification

Back 106

Vesivirus
- Vesicular diseases of cats, cetaceans, primates, skunks, reptiles.

Lagovirus
- Rabbit hemorrhagic disease.

Norovirus
- Norwalk virus.

Sapovirus
- Sapporovirus.

Front 107

Calicivirus properties

Back 107

Icosahedral capsid.
- Nonenveloped.
- small ~25-40nm
- 32 cup-shaped capsomers.
- Hardy in environment.


ssRNA genome.
- Linear
- Positive polarity.
- 7.4-7.7 kb
- 5’ VPg protein – acts like a cap;
- 3’ polyA tail.
- Resistant to heat and detergent.

Front 108

how does the calicivirus genome differ from the picornavirus genome?

Back 108

Notice that the structural proteins are at the 3’ end
of the ORF (vs Picornaviruses 5’ orientation)

Front 109

calicivirus replication

Back 109

Similar to picornaviruses.
Occurs in cytoplasm.

After entry and uncoating, viral genome is translated into a polyprotein that then undergoes cleavage.

One product is viral RNA polymerase.

Carries out transcription of genome.

Some caliciviruses produce subgenomic mRNA (feline, porcine).

Assembly of capsomers, packaging of genome, released by cell lysis.

Front 110

norwalk virus

Back 110

calicivirus

Fecal-oral spread.

Gastroenteritis – diarrhea, vomiting lasting 24-48 hours.

“Cruise-ship virus”

Worldwide; 23 million cases in US every year.

Diagnosed by identification of virus in feces or serology.

Front 111

calicivirus veterinary pathogens

Back 111

Feline calicivirus – upper respiratory tract infection.
- Newer syndrome associated with vasculitis.

Vesicular exanthema of swine – eradicated in US as it resembles FMD; occurs also in marine mammals.

Rabbit hemorrhagic disease – lethal infection, high morbidity and mortality; massive hemorrhages.

San Miguel sea lion virus

Front 112

vesicular exanthema of swine

Back 112

Present in marine mammals (they are the host).
- only animal affected is swine

can enter though skin but normally oro-nasal exposure

Indistinguishable from FMD – eradicated from US by 1956, not known to occur elsewhere.

Systemic infection.

Acute febrile disease with vesicle formation on snout, tongue, teats, oral cavity, and feet.

Most infections occurred from contaminated feed.

When occurred, was also associated with diarrhea, encephalitis, myocarditis, and abortion.

Many antigenic serotypes.

Notifiable.

Front 113

san miguel sea lion virus

Back 113

calicivirus

Same as VE of swine.
- Source of disease for swine.

Abortion and vesicular lesions in sea lions on San Miguel Island.

Carcasses fed to swine transmit virus.

17 types found in variety of sea mammals.

Front 114

rabbit hemorrhagic dz

Back 114

calicivirus

Identified in China in 1984.

Killed nearly half a million rabbits in 1st 6 months.

Hemorrhagic lesions in lungs and liver.

Spread through Europe by 1988 to N. Africa.

Has been found in North America, but only European rabbit susceptible to disease.

high mutation rate b/c RNA so it will probably not work to eradicate rabbits in australia

Highly infectious disease of European rabbits.

Disseminates to liver after entry (ingestion – fecal-oral) leading to necrosis.

Leads to disseminated intravascular coagulation (DIC) and hemorrhages.

Disease in rabbits >2 months of age (?).
- affects older rabbits more

Depression, fever, death.
Hemorrhages and clots seen post mortem.

Mortality 90%; morbidity virtually 100%.

Use for biocontrol of rabbits in Australia.

Vaccine available.

Front 115

feline calicivirus

Back 115

One of two major causes of viral respiratory disease in cats.

Strain variation – impacts diagnostics and vaccines.

Transmitted via fomites, aerosol - contagious.

Lesions primarily in RT:
- Esp URT

Replicates in epithelia.

Conjunctivitis, rhinitis.

Oral ulcers.

Pneumonia with some strains.

Mortality highest in kittens.

Don’t normally see corneal ulcers in these cats.

Some strains very pneumotropic (profound pneumonia, causing death in 48 hours)

Usually fairly mild

New virulent systemic strains
- Hemorrhagic strains noted in recent years.
- Vasculitis.
- Edema, crusting cutaneous lesions, hepatic involvement.
- Unclear pathogenesis.
- High mortality.

Limping kitten syndrome – immune-mediated.

After recovery, affected cats may shed the virus for months or longer from oropharyngeal region.

This is a concern in hoarders

Front 116

calicivirus dx, tx, control

Back 116

Diagnosis
- Virus detection
- Serology

No specific treatment – supportive only.

Control.
- Vaccine for feline calicivirus.
- No vaccine developed for Norwalk nor Hepatitis E virus

Front 117

hepevirus

Back 117

Genus without a family….
- only member is Hepatitis E
- Small (25-35 nm) nonenveloped icosahedral virus.
- Genome ~7000 bases in length.
- 5’ cap
- 3’ poly-A tail
- very similar to calicivirus

Replication in cytoplasm

After uncoating, first ORF is translated – Viral RdRp.

RdRp copies pos genome → neg genome:

From the negative strand, genome length and subgenomic (ORF 2 and 3) length mRNA are made.

Structural and nonstructural proteins made.

Virus is assembled.

Virus is released by cell lysis.

Front 118

Hepatitis E

Back 118

Pathogenesis similar to hepatitis A virus.
- Ingested, spreads to liver.
- Jaundice, malaise, nausea, abdominal pain.
- No persistent infection.
- Most recover.
- Disease seen mainly in 15-40-year-olds.

Another infectious hepatitis

Shed in feces

Sticks around in environment for a long period of time

Affects those in the prime of their life

Most significant in pregnant women (high mortality rate)
- Esp in 3rd world countries

Targets primarily 15-40 yo’s; ill for several weeks - ~2% mortality.

~20% mortality in pregnant women – fulminant hepatic failure.

Four genotypes.
- 1 and 2 humans only
- 3 and 4 infects humans, pigs, other species.

Rodents may be the reservoir.

Similar virus identified in birds.

Front 119

astrovirus

Back 119

Isolated from many mammalian and avian species
Icosahedral 28-35nm nonenveloped.

Replication, structure, pathogenesis similar to norovirus
- Gastroenteritis.
- Many serotypes

Star liked appearance
- Calici/ hepatitis E/ astro are really hard to tell apart

No envelope so hardy in environment

Replication similar to calici

Causes gastroenteritis like norovirus

Front 120

what are the 2 major diseases associated with picornaviridae?

Back 120

polio

foot & mouth dz

Front 121

Picornaviridae classification

Back 121

Enterovirus
- Enteric viruses
- Poliovirus
- Other diseases in veterinary medicine.
- Swine vesicular disease.
- Enteroviruses of cattle, swine, birds, monkeys.

Rhinovirus
- Virus of the common cold.
- Also occur in cattle.

Hepatovirus
- Hepatitis A virus
- Avian encephalomyelitis

Aphthovirus
- Foot and mouth disease virus.
- Other veterinary pathogens, incl equine rhinovirus-1.

Cardiovirus
- Encephalomyocarditis of rodents.
- Theiler’s murine encephalomyelitis virus.

Front 122

Picornaviridae Properties

Back 122

Icosahedral capsid
- Nonenveloped
- 22-30nm (small!)
- 60 capsomers; 4 polypeptides, VP1-4.
- “canyons” between virus proteins in capsid important for interaction with cell receptor.
- Immunity to one doesn’t give immunity to another
- Hardy in environment

Genera vary in acid stability – influences tropism.
- Aphtho unstable below pH7.
- Rhino unstable below pH5
- Others stable at pH3.


ssRNA genome

Positive polarity

~7.5kb

One ORF – 3 regions
- 5’-most: Capsid proteins
- 3’-most: Nonstructural proteins incl protease, RNA pol
3’ Poly-A tail, protein at 5’ end (VPg).

5’ non-translated region highly conserved.
- Important in replication
- Internal ribosomal entry.

Front 123

picornavirus replication occurs where?

Back 123

replication in cytoplasm

doesn't need nuclear fxn

Front 124

picornavirus replication

Back 124

Attachment to cell receptor.
- Members of immunoglobulin superfamily.
- Integrins, other glycoproteins.

Replication occurs in the cytoplasm of the cell.
- Forms pore in cell membrane after attachment, injects nucleic acid.

Genome replication.
- RNA synthesis primed by VPg.
- Viral and cellular proteins involved.

no early and late translation

Viral RNA dependent RNA polymerase transcribes genome.

Full length negative strand made (using positive strand as template); this serves as template for more positive strands.

Early in infection, + strands serves as mRNA; later, packaged in mature virion.

Polypeptides assemble into capsomer (1).

Capsomers assemble into capsid (2).

Nucleic acid packaged (3).

Virions released by cell lysis.

Front 125

how does picornavirus ensure that viral genome is preferentially translated.

Back 125

Host translation interference.
- Cap-binding complex cleaved by viral protease.
- Cellular mRNA uncapped.

Viral message doesn’t need cap.
- Internal ribosomal entry site.
- Genome has 3’-poly A tail.
- Single ORF – polyprotein cleaved post-translationally.

5’-UTR of the RNA folds into a cloverleaf, binds cellular proteins initiating translation

Front 126

picornavirus cellular effects

Back 126

cytopathic effects

ds RNA accumulates (during replication it is ds, but the final product is ss) – stimulates IFN.

RNA synthesis of cells inhibited by viral protein.

Toxic effects of coat proteins.

Altered ionic environment due to altered plasma membrane permeability.

Cellular translation interfered with.
- Viral mRNA out-competes host mRNA.
- Inactivation of translation factors.

Front 127

enteroviruses

Back 127

picornaviridae

Attacks from the intestine (from the lumen of the intestine)
- Attacks epithelial cells and lymphoid tissue in intestine

Occur in most vertebrates.

Fecal-oral spread.

Survives transit through stomach

Replicates in intestinal lymphoid tissue.

Stable at pH of 3

May spread systemically via bloodstream or neural infection.

Important human pathogen.
- Polio virus
- Enteric disease
- Respiratory disease
- Myocarditis
- Meningitis
- Rash