Test 2- Adenoviridae

Question 1

Family: Adenoviridae

 Morphology:

Answer 1

 Non-enveloped, precisely hexagonal in outline.
 Icosahedral symmetry, 70–90 nm in diameter.
 The capsid shell consists of 720 hexon subunits arranged as 240 trimers.
 12 vertex penton capsomers each with a fiber protrude from the surface of capsid.

Question 2

Family: Adenoviridae

 Genome & Replication:

Answer 2

 Genome & Replication:

• non-segemented, linear, double- stranded DNA of 35-36 kb
   Replication takes place in the nucleus by a complex program of early and late transcription (before and after DNA replication).

 Virions are released by cell lysis.

 Intranuclear inclusion bodies are formed, containing large numbers of virions, often in para-crystalline arrays.

Question 3

Answer 3

Inclusion bodies

Question 4

Family: Adenoviridae

General Properties

Answer 4

 Many adenoviruses agglutinate red blood cells. Hemagglutination occurring when the tips of penton fibers bind to surface receptors on RBC.

 Some viruses are oncogenic in laboratory animals

 Adenoviruses are relatively stable in the environment, but are inactivated easily by common disinfectants.

 Most of the adenoviruses have narrow host ranges.

Question 5

Family: Adenoviridae

 Pathogenesis:

and Immunosuppression

Answer 5

 Many adenoviruses cause acute respiratory or gastroenteric disease of varying severity.- Mostly subclinical infections.

 Penton and fiber proteins of the capsid are toxic to cell.
————–Inhibition of cellular mRNA export to nucleus and protein synthesis.

————– Cell rounding and tissue damage.

 Immunosuppression: Adenoviruses encode proteins (E3, E1A, etc.) that suppress host immune and inflammatory responses.

————– Inhibition of class I major histocompatibility antigen transport by E3/19K.

—————- Tumor necrosis factor-induced apoptosis is inhibited by adenoviral E3/14.7K

—————– Blocking of interferon-induced protein kinase R-mediated inhibition of viral

protein synthesis.

——————–Modulate antiviral inflammatory responses by inhibiting nuclear factor κB (NF κ

B) transcriptional activity.

κ : Kappa

Question 6

 Long periods of latency.

Answer 6

 Virus persists in lymphoid and other

tissues, such as tonsil, adenoids, and Peyer’s patches.

 Reactivated in immunocompromised animals.

 Can be highly pathogenic in immunodeficient animals.

Question 7

 Oncogenesis:

Answer 7

Under specialized conditions, some adenoviruses have been shown to be oncogenic. E1A and E1B gene products are associated with cell transformation.

E1A: Inactivate Rb protein

E1B: Inactivate p53 protein

Family: Adenoviridae

Oncogenesis

Question 8

Genus: Mastadenovirus

Answer 8

Mammalian adenoviruses

 A single penton fiber projects from each vertex

Question 9

Genus: Aviadenovirus

Answer 9

Avian adenoviruses

 Each penton fiber is bifurcated, appear as two fibers extending from each penton base

Question 10

Infectious Canine Hepatitis (ICH, Rubarth’s Disease)

Answer 10

Distinguished from Canine Distemper (CD; Family: Paramyxoviridae) by Rubarth in 1947.

Showed that ferrets are resistant to ICH, but susceptible to CD(in ferrets- causes mucropurlent discharge)

Question 11

Infectious Canine Hepatitis (ICH, Rubarth’s Disease)

Etiology, Host, transmission

Answer 11

 Etiology: Canine adenovirus -1 (CAV-1).

 Host: Canidae (domestic and wild) and Ursidae (bears)

 Distribution: Worldwide

 Transmission:
 Acute infection: CAV-1 is found in all secretions and excretions.

 Afterwards, Virus shed in urine for at least 6 to 9 months.

 Route: Oronasal transmission

 Contact with:

 Secretions/excretions of infected dog.

 Contaminated fomites.
 Ectoparasites can harbor CAV-1

Question 12

Pathogenesis of Infectious Canine Hepatitis

 Sites of virus replication:

Answer 12

 Sites of virus replication:

 Macrophages

 Kupffer cells
 Hepatocytes
 Vascular endothelium of different organs including CNS

 Parenchymal cells of organs and tissues

 Liver, kidneys, spleen and lungs are main target organs.
 Initial cellular injury to liver, kidney, and eye is associated with cytotoxic effects of virus.

Question 13

Pathogenesis of Infectious Canine Hepatitis

Hepatitis

Answer 13

 At time of infection, dogs already with sufficient antibody titers (>500) show little clinical evidence of disease.

 In acute cases, sufficient antibody response by day 7 post-infection (PI) [>500 antibody reponse by day 7 PI] clears virus from blood and liver and restricts hepatic damage.

 Persistently low antibody titer (<4) will lead to widespread centrilobular to panlobular hepatic necrosis.

 Partial immunity (antibody titer >16, but <500) may result in chronic active hepatitis and hepatic fibrosis.

Question 14

Answer 14

Swollen, mottled liver with round lobar edges

Question 15

Answer 15

Canine liver acute necrosis

Question 16

Answer 16

Basophilic intranuclear inclusion bodies

Question 17

Answer 17

Pathogenesis of Infectious Canine Hepatitis Cirrhosis in chronic cases

Cirrhosis of Liver

Question 18

Pathogenesis of Infectious Canine Hepatitis

 Kidney:

Answer 18

Acute infection, Glomerulonephritis.

Acute Glomerulonephritis

Basophilic Inclusion Bodies

Chronic kidney lesions may result from immune-complex reactions after recovery from acute or subclinical disease.

Question 19

Pathogenesis of Infectious Canine Hepatitis

Ocular Lesions

Answer 19

Corneal edema (Blue eye):

 Occurs in about 20% of natural infections.
 Less than 1% of dogs after S/C MLV-CAV-1 vaccination.

 Seen in dogs during recovery, or chronic cases- SEEN IN LATER STAGES OF THE DISEASE

Question 20

Answer 20

Pathogenesis of Infectious Canine Hepatitis Ocular Lesions

Question 21

Ocular Lesions

Answer 21

1. During viremia, CAV-1 enters the eye via the uveal tract.
2. CAV-1 localizes in endothelium of choroid and causes mild uveitis.
3. By 4-6 days post infection, virus enters the aqueous humor from the blood and replicates in corneal endothelial cells.

By day 7, Severe anterior Uveitis and Corneal Edema (Blue Eye) develop.

How Corneal edema develops?
4. CAV-1 antibody production increases, and formation of viral-antibody immune complexes.

5. This result in Complement activation, neutrophil chemotaxis.
6. Cause extensive damage to corneal endothelium.
7. Disruption of intact corneal endothelium allows aqueous to enter the cornea.
8. Accumulation of edematous fluid within corneal stroma results in corneal edema.
9. From days 8-21, macrophages remove the immune complexes and corneal endothelium regenerates, re-establishing the hydrostatic gradient.
10. Clearing of corneal edema.

Damage to the corneal endothelium, so fluid enters the cornea

Question 22

Complications from Infectious Canine Hepatitis

 Disseminated intravascular coagulation (DIC)

Answer 22

Results from:
 Damage to endothelium
 Inability of diseased liver to remove activated clotting factors

Question 23

Answer 23

Complications from Infectious Canine Hepatitis

 Bacterial Pyelonephritis resulting from renal damage.

secondary bacterial infection

Question 24

Infectious Canine Hepatitis

 Clinical signs:

Answer 24

 Most frequent in dogs less than 1 year age
 Concurrent parvoviral or distemper infection worsens the prognosis.

 Unvaccinated dogs of all ages are susceptible.
 Most infections are asymptomatic
 Signs vary from a slight fever to death.

Question 25

Infectious Canine Hepatitis (ICH)

 Clinical signs:
 Peracute cases:

Answer 25

 Peracute cases: Severely infected dogs become moribund and die within few

hours after onset of clinical signs.

Question 26

Infectious Canine Hepatitis (ICH)

 Clinical signs:

 Acute cases:

Answer 26

 Acute cases:
Clinical signs in dogs that survive acute viremic phase:

 Fever of >104°F (40°C), Depression, Anorexia

 Vomiting

 Occasionally abdominal pain, Abdominal tenderness and Hepatomegaly

 Intense hyperemia or petechiae hemorrhages of the oral mucosa.

 Pale mucous membrane, Jaundice

 Enlarged tonsils, swollen lymph nodes

 Subcutaneous edema of the head, neck, and trunk

 CNS involvement is unusual and is typically the result of vascular injury.

Convulsions may appear from forebrain damage.

 Icterus is uncommon in acute ICH

 Corneal edema and anterior uveitis occur when clinical recovery begins.

 Encephalitis is more commonly seen in Foxes,

Question 27

Infectious Canine Hepatitis (ICH)

 Diagnosis:

 Clinical signs

 Necropsy and Histopathology:

Answer 27

 “Paint-brush” hemorrhages on the gastric serosa, lymph nodes, thymus, pancreas, and subcutaneous tissues.

 Centrilobular necrosis in liver, with neutrophilic and monocytic infiltration, and hepatocellular intranuclear inclusions.

 Grayish white foci may be seen in the kidney cortex of recovered dogs or dogs

with chronic disease.

Question 28

nfectious Canine Hepatitis (ICH)

 Diagnosis:

 Biochemistry and hematology:

Answer 28

 Leukopenia persists throughout febrile or early period

 Increased ALT and AST due to hepatic injury
 Proteinuria
 Prolonged prothrombin time, thrombocytopenia

Question 29

Virus isolation, antigen detection, nucleic acid detection,

Answer 29

 Virus isolation: Urine, blood, tissue homogenates, etc.
 Antigen detection: FAT
 Nucleic acid detection: PCR
 Paired serum tested( need 2 samples) using virus neutralization, ELISA or HI

Question 30

Infectious Canine Hepatitis (ICH)

 Treatment:

Answer 30

Treatment is symptomatic and supportive. The goals of therapy are to limit secondary

bacterial invasion, support fluid balance, and control hemorrhagic tendencies.

Question 31

 Immunity:

Infectious Canine Hepatitis (ICH)

Answer 31

 Recovered animals are immune to systemic form of disease.

 Maternal antibodies interferes with active immunization until puppies are 9 to 12 weeks of age.

 Attenuated CAV-1 live vaccines have produced transient unilateral or bilateral opacities of the cornea. Vaccine virus can cause mild subclinical interstitial nephritis, and may be shed in urine. Discontinued in many countries.

 CAV-2 attenuated live virus strains provide cross-protection against CAV-1. CAV-2 attenuated vaccines are preferentially used because they have very little tendency to produce corneal opacities or uveitis, and the virus is not shed in urine. THIS IS THE BEST VACCINE

 Primary Vaccination: Healthy dogs between 6 and 12 weeks of age.  Revaccination: 14 to 16 weeks of age

Question 32

Canine Infectious Tracheobronchitis (ITB, Kennel Cough)

Etiology, Transmission

Answer 32

Kennel cough is a self-limiting upper respiratory disease of dogs.

 Etiology: Multiple.
CAV-2 (Canine Adenovirus-2) and Bordetella bronchiseptica (primary pathogen) are most prevalent.
 Also:

 Canine Parainfluenza Virus, Canine Distemper Virus
 Role questionable: Canine adenovirus-1, Canine reoviruses 1, 2 & 3, Mycoplasma sp

 Transmission:
 Highly contagious. Via aerosolized droplets.
 Stress, unfavorable conditions increases severity of disease.

Question 33

Clinical Signs,

Uncomplicated or Complicated

Answer 33

Canine Infectious Tracheobronchitis (ITB, Kennel Cough)

 Clinical signs: Incubation period 1-3 days.

 Uncomplicated ITB:

 The prominent clinical sign is paroxysms of harsh, dry coughing, followed by etching

and gagging.

 Coughing causes a high pitched “honking” sound.

 Rhinitis, serous nasal discharges, sometimes conjunctivitis

 “Complicated” ITB:
 Severe pneumonia or bronchopneumonia  Life threatening

Question 34

Diagnosis, Treatment, Immunity

Answer 34

Canine Infectious Tracheobronchitis (ITB, Kennel Cough)

 Diagnosis:
 Clinical signs, coughing is easily induced by gentle palpation of the larynx or trachea.  Nucleic acid detection, serology, virus isolation same as CAV-1

 Treatment:
Antitussives (a cough suppressant), when used in conjunction with bronchodilators, are often considered the standard treatment for dogs with ITB. Antitussive drugs serve to interrupt the cough cycle.

 Immunity:
Modified-live virus vaccines against distemper, parainfluenza, and CAV-2, which also provides protection against CAV-1.

Question 35

Equine Adenovirus

Answer 35

 Equine Adenovirus-1 (EAV-1) and Equine Adenovirus-2 (EAV-2).

 Most equine adenovirus infections are asymptomatic or present as mild upper or lower respiratory tract disease.

 EAV-1 is associated with severe respiratory disease in Severe Combined ImmunoDeficiency (SCID) foals.- Foals do not have an immune system

 As maternal antibody wanes, these foals become susceptible to adenovirus infection.

Infection is progressive, and these foals invariably die within 3 months of age.

Question 36

Equine Adenovirus

Immunodeficiency in SCID foals:

Answer 36

 V(D)J recombination is essential for expression of antigen receptors on B and T lymphocytes.

 Without these receptors, B and T lymphocytes do not differentiate and lymphoid tissue fails to develop.

 In SCID foals, there is a mutation in the allele encoding for a DNA-dependent protein kinase (DNA-PK) that is needed for lymphocyte V(D)J recombination.

 As a result, there is severe immunodeficiency.

Question 37

Equine Adenovirus

 Clinical signs in SCID foals:

Answer 37

 Severe bronchiolitis and pneumonia. Respiratory distress and related signs.
 May develop generalized EAV infections, as virus destroys cells of different organs, such as Pancreas, GI tract, Renal and Bladder.

Question 38

chicken adenovirus

Answer 38

inclusion body hepatitis or egg drop syndrome

Question 39

Duck

Answer 39

hepatitis (rare)

Question 40

Quail

Answer 40

Bronchitis

Question 41

Turkeys

Answer 41

Hemorrhagic enteritis Egg drop syndrome

Question 42

Pheasants

Answer 42

Marble spleen disease