Hepatic viruses Flashcards
Explain why infectious agents affect the liver
- Major organ encountered in line after penetration of gut (via portal vein)
- Major organ that filters blood directly from heart
- Easy to get there and establish infection
- Liver provides hepatocyte-specific cofactors/nutrients to pathogens
- Liver micro RNAs can drive irus RNA replication
- Ineffective host anti-viral immune response in liver
Give an example of how the liver provides liver-specific cell cofactors/nutrients
- High arginine requirement of hepatotropic adenoviruses
- Arginine rich proteins in the liver
- Arginine supplied to hepatotropic adenoviruses
Explain how liver micro RNAs can drive virus RNA replication
- Via activation of viral RNA 3’ untranslated region
- Human hep C infection using micro-RNA 122
- Micro-RNAs are non-cpding regions of genomes, expressed in tissue specific way
- Regulate gene expression
- Viruses hijack this for own RNA replication and regulation
List the principle outcomes of virus or pathogen infection in the liver
- Acute or chronic hepatitis
- Sometimes with hepatomegaly
- Cytotoxic T cell and NK cell mediated damage
- Dysregulation of normal liver function (jaundice, hypoproteinaemia, hypoglycaemia, anaemia)
What are the 2 types of hepatic virus?
- Those affecting the liver predominantly (CA-1 of ICH)
- Those targeting the liver as part of generalised systemic infection
What is the majority of liver damage in infection caused by?
- Some due to the pathogen/virus
- most due to immune response to infected cells
- Cytotoxic lymphocytes dysregulated by infection causing tissue damage
- Excess host immune response to infectious agent
What type of hepatic virus causes canine hepatitis and name the causative agent
- Hepatotropic virus (those principally affecing the liver)
- Canine adenovirus type 1
Describe the pathogenesis of canine hepatitis
- Can cause periacinar necrosis (arouns around centre of lobules)
- Tropism for endothelium (widespread haemorrhages, particular of serosal surface and hepatocytes)
- Recovering animals may show immune mediated uveitis with corneal opacity
- Damage to blood vessels leading to haemorrhage
- Tissue damage mostly caused by host immune response, only some caused by virus
Describe the epidemiology of canine hepatitis
- Highly infectious disease of young dogs
- Spread via uriine of infected animals over long period of time
- Contagious disease of dogs, occurs worldwide
- Mortality highest in puppies
Describe how an animal becomes infected with canine hepatitis
- Ingestion of urine, saliva, faeces from infected animal
- Replicates in tonsils, larynx, Peyer’s patches as primary sites
- Progresses to liver, eyes, kidneys for secondary replication
Describe the clinical signs of canine hepatitis
- Apathy
- Anorexia
- Thirst
- Conjunctivitis
- Ocular and nasal discharge
- Abdominal pain
- Vomitign
- Blood clotting affected, leads to haemorrhages in affected tissues (gums for example)
Describe the appearance of a liver affected by canine hepatitis
- Areas of necrosis
- Adenoviral inclusion bodies in nuclei of Kupffer cells and parenchymal cells
Describe canina adenovirus type 1
- Causative agent of canine hepatitis
- Adenoviridae family
- Non-enveloped
- Linear double stranded DNA
- Icosahedral
- Capsid consists of hexons and pentons, fibres protrude from these that contain cell attachment roteins
- Virus replicates in nuelcieus of host cells
Describe the immune response to canine hepatitis
- Survivors immune to reinfection
- Solid immune response
Describe the control of canine hepatitis
Live attenuated virus or killed virus vaccine
What causes the “blue eye” opacity seen in canine hepatitis?
- Host immune resopnse
- Caused by immune complex deposition in glomeruli of kidney and cornea in eyes
What is the causative agent of malignant catarrhal fever in cattle/deer?
- 2 viruses
- Alceaphine herpesvirus 1 (AIHV-1, reservoir in wildebeest, found in Africa)
- Ovine herpesvirus-2 (OvHV-2, reservoir in sheep, worldwide)
What type of virus causes malignant catarrhal fever?
One that cuases systemic disease that includes liver pathology
Describe the pathogenesis of malignant catarrhal fever
- Lympho-proliferation and tissue necrosis
- Infection of natural host (sheep, wildebeest) no disease
- Infection of disease-susceptible host (cattle, deer, bison, pigs) erratic infection, results in dramatic pathological changes and death
- Virus invades cells
- Destroys epithelium and endothelium
- OvHV-2 infects via oro-nasal pharyngeal port of entry
- Gets into lymphocytes
- Presence of virus in ytotoxic T/NK cells associated with indiscriminate (non-MHC-linked) destruction of tissues
- Vasculitis and epithelial damage in multiple tissues causes death
Describe the clinical signs of malignant catarrhal fever
- Fever, depression, lack of appetite
- Nasal discharge
- Conjunctivitis and corneal opacity
- Lymph node hyperplasia
- Lesions in mouth and GIT
- Lesions in skin and muzzle
- Lesions in CNS
- Death (recovery rare)
Describe the presence of malignant catarrhal fever in British/European cattle
- Relatively resistant
- Sporadic infection, only affects a few at a time
Describe the transmission of malignant catarrhal fever
- All lambs have virus within 2 months of age
- Peak excretion around 7-10 moths, no disease
- Spreads from sheeo to cattle
- Can be spread via humans
- NO horizontal transmission between cattle
Explain why transmission of malignant catarrhal fever is not possible between cattle
- Virus undergoes incomoplete replication cycle
- No enveloping
- Cannot escape cells and be excreted
Describe the control of malignant catarrhal fever
- No vaccine
- Avoid having sheep and cattle together
- Maintain high biosecurity humans going between sheep and calves
