Test 2- Adenoviridae Flashcards
Family: Adenoviridae
Morphology:
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.
Family: Adenoviridae
Genome & Replication:
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.
Inclusion bodies
Family: Adenoviridae
General Properties
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.
Family: Adenoviridae
Pathogenesis:
and Immunosuppression
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
Long periods of latency.
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.
Oncogenesis:
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
Genus: Mastadenovirus
Mammalian adenoviruses
A single penton fiber projects from each vertex
Genus: Aviadenovirus
Avian adenoviruses
Each penton fiber is bifurcated, appear as two fibers extending from each penton base
Infectious Canine Hepatitis (ICH, Rubarth’s Disease)
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)
Infectious Canine Hepatitis (ICH, Rubarth’s Disease)
Etiology, Host, transmission
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
Pathogenesis of Infectious Canine Hepatitis
Sites of virus replication:
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.
Pathogenesis of Infectious Canine Hepatitis
Hepatitis
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.
Swollen, mottled liver with round lobar edges
Canine liver acute necrosis
Basophilic intranuclear inclusion bodies
Pathogenesis of Infectious Canine Hepatitis Cirrhosis in chronic cases
Cirrhosis of Liver
Pathogenesis of Infectious Canine Hepatitis
Kidney:
Acute infection, Glomerulonephritis.
Acute Glomerulonephritis
Basophilic Inclusion Bodies
Chronic kidney lesions may result from immune-complex reactions after recovery from acute or subclinical disease.
Pathogenesis of Infectious Canine Hepatitis
Ocular Lesions
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
Pathogenesis of Infectious Canine Hepatitis Ocular Lesions
Ocular Lesions
- During viremia, CAV-1 enters the eye via the uveal tract.
- CAV-1 localizes in endothelium of choroid and causes mild uveitis.
- 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.
- This result in Complement activation, neutrophil chemotaxis.
- Cause extensive damage to corneal endothelium.
- Disruption of intact corneal endothelium allows aqueous to enter the cornea.
- Accumulation of edematous fluid within corneal stroma results in corneal edema.
- From days 8-21, macrophages remove the immune complexes and corneal endothelium regenerates, re-establishing the hydrostatic gradient.
- Clearing of corneal edema.
Damage to the corneal endothelium, so fluid enters the cornea
Complications from Infectious Canine Hepatitis
Disseminated intravascular coagulation (DIC)
Results from:
Damage to endothelium
Inability of diseased liver to remove activated clotting factors
Complications from Infectious Canine Hepatitis
Bacterial Pyelonephritis resulting from renal damage.
secondary bacterial infection
Infectious Canine Hepatitis
Clinical signs:
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.
Infectious Canine Hepatitis (ICH)
Clinical signs:
Peracute cases:
Peracute cases: Severely infected dogs become moribund and die within few
hours after onset of clinical signs.
Infectious Canine Hepatitis (ICH)
Clinical signs:
Acute cases:
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,
Infectious Canine Hepatitis (ICH)
Diagnosis:
Clinical signs
Necropsy and Histopathology:
“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.
nfectious Canine Hepatitis (ICH)
Diagnosis:
Biochemistry and hematology:
Leukopenia persists throughout febrile or early period
Increased ALT and AST due to hepatic injury
Proteinuria
Prolonged prothrombin time, thrombocytopenia
Virus isolation, antigen detection, nucleic acid detection,
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
Infectious Canine Hepatitis (ICH)
Treatment:
Treatment is symptomatic and supportive. The goals of therapy are to limit secondary
bacterial invasion, support fluid balance, and control hemorrhagic tendencies.
Immunity:
Infectious Canine Hepatitis (ICH)
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
Canine Infectious Tracheobronchitis (ITB, Kennel Cough)
Etiology, Transmission
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.
Clinical Signs,
Uncomplicated or Complicated
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
Diagnosis, Treatment, Immunity
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.
Equine Adenovirus
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.
Equine Adenovirus
Immunodeficiency in SCID foals:
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.
Equine Adenovirus
Clinical signs in SCID foals:
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.
chicken adenovirus
inclusion body hepatitis or egg drop syndrome
Duck
hepatitis (rare)
Quail
Bronchitis
Turkeys
Hemorrhagic enteritis Egg drop syndrome
Pheasants
Marble spleen disease
