Calicivirus

Calicivirus

1. Replication

   • 1. Virus attachment to plasma membrane
     • FCV dual receptors
       • Sialic acid
       • Junctional Adhesion Molecule-1
     • Epithelial cell structure stained for junction proteins
   • 2. Entry to cytoplasm/nucleus
     • Receptor binding causes virus to change shape
       • Becomes more hydrophobic
     • Clathirin assembled
     • Endosomal acidification important
     • Normally meets URT first
   • 3. Un-coating of virus particle
   • 4. Synthesis of mRNA and protein
     • Genome is +ve sense RNA, v similar to FMD
     • Has 3 open reading frames
       • ORF1 codes for a polyprotein
         • Cleaved to form helicase, protease and RNA polymerase
       • Capsid proteins VP1 and VP2 from ORF 2 and 3 made from short +mRNA
     • Makes more copies of RNA before copying structural genes
   • 5. Replication of nucleic acid
     • Genome replication via RNA intermediate
   • 6. Virus assembly
     • Calicivirus self assembles in cytoplasm
   • 7. Exit of virus from cell
     • Cell lysis and virus release
     • FCV rapidly cytotoxic in cell culture
     • 24hrs extensive lysis of epithelial cells

2. Feline calicivirus

   • Polymorphisms
     • Evolves by mutation and recombination
     • Calicivirus polymerases do not proof read
       • Different isolates have many sequence variations
       • High rate of mistakes
     • FRET = fluorescence resonance energy transfer
     • Peak is due to H bond melting
       • Flash of light produced
     • Not all mutations matter
       • Neutral
       • Truncated protein
       • Warping effect
       • Mutation hot spots
         • Build up of aa substitutions on non-critical surface loops
           • No structure importance, so can build up
           • Can affect antibody binding
             • This is how persistent and chronic infections occur
             • Dodges immune response
             • Antigenic drift seen in cats with persistent infection
               • Evision of antibodies drives virus variation
                 • Pseudospecies
   • Vaccination
     • Several monotypic vaccines available
     • Broadly cross protective IgG antibody
     • Live attenuated IM not suitable for pregnant cats
       • May be pathogenic by mucosal route
       • Inactivated vaccine is safe for gravid cats
     • Grow in cell culture
       • Not well adapted to living in cat
         • Is thus a 'weaker' strain
         • Useful for stimulating am immune response
     • Live temperature attenuated intranasal vaccine
       • Demonstrates virus interference rapidly protective
         • Grow strain at low temp
         • Does well to stimulate immunity at tip of nose
           • Point of entry of disease
           • Without entry to lungs and more serious clinical disease
   • 40% of feline upper respiratory infections
     • Aerosol
     • JAM-1 - infection of respiratory epithelial cells
       • Released virus spreads locally
         • Also viraemic spread
     • 'Holes' seen on top of tongue
     • Rapidly cytotoxic loss of epithelial function
   • Pathology
     • Local inflammation
       • Cytokine and interferon release
         • Causes fever, sickness behaviours, depression, loss of appetite
     • Increased secretions
       • Start as serous, become mucous
     • Sensitisation of local nerves
   • Clinical signs
     • Salivation
     • Lacrimation
     • Sneezing
     • Clinical disease rare in adults
     • More severe disease in v young kittens
   • Pulmonary lesions, oedema, pneumonia (due to deeper pulmonary lesions), joint infection (this can be quite common – presents as a reluctance to move)
   • Diagnosis
     • Virus isolation
     • PCR
   • Viaemic Systemic Disease
     • Outbreaks in adult vaccinated cats
     • Clinical signs
       • Severe respiratory symptoms
       • Persistent fever
       • Severe systemic inflammatory response
       • Cutaneous oedema
       • Ulceration
       • Pancreatitis
       • Hepatic necrosis
       • Multi-organ failure
       • DIC and haemorrhage
         • Often a terminal event
           • No more clotting
     • 70% mortality

3. Rabbit haemorrhage disease virus

   • High morbidity and mortality in rabbits > 2 months old
     • Does not affect neonates
   • Affects monocyte macrophages
   • Clinical signs
     • Severe lesions in lungs, spleen, lymphoid tissue, kidney and liver
       • Within 36 hrs of infection
       • Hepatocytes and macrophages lining ducts
     • Fever, lethargy, pulmonary oedema, hepatic and vascular necrosis
     • Haemorrhgaes and DIC
     • 'Nutmeg' liver on EM
   • Highly contagious
     • Spread in faeces and resp secretions
     • Passive transmission by insects
       • Mechanical
   • Not been grown in cell culture
   • RHDV receptor
     • Complex carbohydrates on histological/blood group antigens
       • Hence different rabbit susceptibility
         • Different blood group, different susceptibility
         • Depends on antigen type and strain
   • Used for bio-control of rabbits in Australia and New Zealand
   • Only known to affect European rabbits and European hare
     • Not American rabbits
     • Less virulent strains in Europe may be providing some immunity in wild rabbits
   • Passive protection transferred by neutralizing serum antibody
   • Vaccine
     • Inactivated virus from rabbit tissue
     • Dual myxomatosis/RHVP60 recombinant pox virus protects against both diseases
   • RHDV (b)
     • New variant originating in France
     • No cross protection with vaccines based on (a)
     • Has been reported in UK wild and domestic rabbits

4. Characteristics

   • Genome
     • +ve sense RNA
   • Structure
     • Non enveloped icosahedron
     • Capsomers arranged in rings on the faces
       • 32 characteristic cup depressions

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