Virology - paramyxovirus, rhabdovirus and papillomavirus Flashcards
What classification of virus are paramyxoviruses?
Single stranded negative sense RNA virus
Group 5 of the Baltimore classification system
What common human diseases are paramyxoviruses?
Mumps, measles, main resp infections in infants
What is the morphology of paramyxoviruses?
Pleiomorphic - different depending on genus, eg. spherical, filamentous, asymmetric
When do paramyxoviruses have filamentous structure?
When they have more matrix proteins in their membrane
Does paramyxovirus have a lipid envelope?
Yes
What symmetry is the paramyxovirus nucleocapsid?
Helical
What are the two types of attachment proteins on the paramyxovirus envelope?
Haemagglutinin-neuraminidase
Or a glycoprotein
What does the attachment protein do on the paramyxovirus envelope?
Allow the virus to bind to cell surface receptors
What does the fusion protein do on the paramyxovirus envelope?
Causes the viral envelope to fuse with the host cell membrane
What is the most abundant protein in the virion?
Matrix protein
What is the role of the matrix proteins?
Help assemble the virions by providing a structural link between the envelope glycoproteins and their ribonuclear protein
What does the paramyxovirus have on the ends of its genome?
No 5’ cap and no poly-A tail
What is positive sense RNA the same as?
mRNA
Is the paramyxovirus genome segmented?
No
What makes the RdRp from paramyxovirus genome?
The L (large) protein and the P (phospho) protein
What is transcriptional polarity?
When RdRp falls off genome so the genes at the 3’ end get transcribed more
What receptor does paramyxovirus use to enter epithelial cells?
Sialic acid
What mechanism does paramyxovirus use to enter cells?
Receptor mediated endocytosis
What is syncytia?
Fusion of an infected cell with neighbouring cells making large multinucleated cells
What causes syncytia?
Viral fusion proteins
What does paramyxoviruses cause to RBCs?
Haemagglutination
What are two veterinary examples of paramyxoviruses?
Canine distemper virus
Rinderpest
What animals does canine distemper virus affect?
Dogs, foxes, large cats, badgers, seals
How does canine distemper virus enter the host?
Through alveolar macrophages and dendritic cells in the respiratory tract
What is the SLAM molecule used for in canine distemper virus?
Getting into immune cells and therefore the lymphatic system
What is the nectin molecule used for in canine distemper virus?
Getting into epithelial cells in respiratory tract
How is canine distemper virus transmitted?
Aerosols
What does canine distemper virus cause after infection of lymphatic system?
Cytolysis of lymphocytes and drop in WBCs causing immunosuppression
Then systemic disease occurs
What cells does canine distemper virus infect in the CNS?
Neurones and glial cells
What does canine distemper virus cause in animals that do not recover from the virus?
Demyelination and encephalitis, neurological signs and death
What are the symptoms of canine distemper virus?
Initial infection - flu like symptoms
Later stages - neuro signs, thickening of nose and foot pads sometimes
How is canine distemper virus diagnosed?
Blood and urine tests PCR Serology - ELISA Stain for antigens in lymph nodes Haemagglutination assay
How is canine distemper virus treated?
No cure - supportive
Antibiotics for secondary infections
What kind of vaccine is used for canine distemper virus?
Modified live CDV vaccine
Heterotypic measles virus vaccination - good for overriding maternal antibodies
Is rinderpest a big problem?
No - eradicated in 2011
Is still a notifiable disease
What are the symptoms of rinderpest?
Ulcerating sores in soft palate Fever Diarrhoea Weakness Death in 10 days
How is rinderpest spread?
Contaminated water
Direct contact
Aerosols
How was rinderpest controlled?
Live attenuated virus vaccine
Quarantining of transported animals
What is the classification of rhabdoviruses?
Negative sense single stranded RNA
Group 5
What do rhabdoviruses infect?
Vertebrates, invertebrates and plants
What is the symmetry of the rhabdovirus nucleocapsid?
Helical
Does rhabdovirus have an envelope?
Yes
What three proteins make up the rhabdovirus nucleocapsid?
L protein - RdRp
P protein - viral polymerase
N protein - nucleoprotein
What genus is rabies in?
Lyssavirus
How is rabies transmitted?
Bites from rabid dogs - 99%
What is the lyssavirus that is present in the UK?
European bat lyssavirus
(not the same as the classic rabies virus)
Very low numbers
What receptors does rabies virus G glycoprotein bind to?
Acetyl choline receptor on muscle cells
NCAM and P75 neurotrophin receptor on neurons
Where does rabies viral replication occur?
Cytoplasm after being released from the endosome
Where does the rabies virus bud from?
Membranes in the cytoplasm of neurones eg. SER (doesnt leave cell)
Plasma membranes of salivary gland epithelial cells (leave cell)
What causes the behavioural symptoms of rabies?
Infection of the limbic system
What are the two forms of rabies symptoms?
Excitive/furious phase
Paralytic/dumb phase
What are the symptoms of the excitive phase of rabies?
Hyperactivity Hypersalivation Hydrophobia Agitation Coma Death
What species is paralytic phase of rabies found in?
Ruminants and horses
What are the symptoms of paralytic rabies?
Flaccid paralysis spreading from the site of the bite
Death from resp failure
How does the virus spread from the brain to he salivary glands?
Via symp and parasymp nerves
When is rabies virus shed?
Shed before symptoms appear, time depending on the species
How is rabies diagnosed?
Suspected animal killed and brain tissue collected
Immunohistological assessment of tissues
PCR of tissues and saliva
What is the vaccine plan for rabies called?
Pre-exposure prophylaxis (PREP)
Giving oral or injected vaccines before contracting the virus
How is a case of rabies in humans treated?
Post-exposure prophylaxis within 24 hours:
Clean wound
Give dose of human rabies immunoglobulin/antibody
Give vaccine on days 0, 3, 7 and 14
What is the classification of papillomavirus?
Double stranded DNA - circular
Group 1
Does papillomavirus have an envelope?
No
What symmetry is the papillomavirus nucleocapsid?
Icosahedral
What is found on the outer structure of a papillomavirus?
Capsid proteins L1 (major one) and L2
These are hypervariable amino acid loops
Which genes/proteins on the papillomavirus genome are non-structural/regulatory?
Early proteins/genes - E1-8
What do papillomaviruses use to replicate?
Host cell nuclear machinery/replication factors/enzymes
Because papillomavirus doesnt encode for a polymerase
What does papillomavirus E1 protein do?
Is a helicase that unwinds the viral DNA
What cells do papillomaviruses infect/replicate in?
Stratified squamous epithelial cells and mucosal epithelial cells
Which cells are infected by papillomavirus initially?
Basal keratinocytes via fissues/wounds
How does papillomavirus enter cells?
Clathrin-dependent endocytosis after binding to heparin sulphate
Where is the viral genome replicated in papillomaviruses?
Nucleus
How does papillomavirus exit cells?
Cell death
Often just when cells are replaced naturally
What does E5 cause in papillomaviruses?
Increase in cell division via various methods
What are the three methods E5 from papillomaviruses uses to affect host cells?
Cell cycle dysregulation
Contact inhibition
Affects immune response
How does E5 cause cell cycle dysregulation in papillomaviruses?
It binds to platelet derived growth factor receptors (PDGF-R)
This induces the cell to keep dividing
How does E5 cause contact inhibition in papillomaviruses?
It disrupts gap junction signalling
So cells cant tell they are close to other cells so dont stop dividing
How does E5 affect the immune response to cells infected with papillomavirus?
It stops MHC receptors so virally infected cells arent recognised by the immune system
How does E6 affect papillomavirus infected host cells?
It destroys the p53 transcription factor which induces apoptosis in virally infected cells
So prevents apoptosis
How does E7 affect papillomavirus infect host cells?
Interacts with suppressor proteins so there is no suppression of transcription factors and the cell cycle is uncontrolled
Where does papillomavirus viral protein production, viral gene expression and viral assembly occur?
Upper differentiated layers of stratum spinosum and granulosum of squamous epithelial cells
Where does papillomavirus only affect affect?
Keratinocytes - only cells in the epithelium so skin and GI tract
What papillomavirus viral genes are expressed in the basal layer of the epithelium?
E6 and E7
What papillomavirus viral genes are expressed in the upper layers of the epithelium?
All genes, early and late
What happens to the papillomavirus in the upper layers of the epithelium?
DNA replication and viral gene expression is upregulated
Viral copy number is amplified and genomes are encapsulated
These exit the cell as infectious viral particles
What are two papillomavirus diseases that affects cows?
Bovine alimentary papilloma carcinoma
Enzootic haematuria
Where does bovine alimentary papilloma carcinoma affect in the body?
Oesophagus, rumen and reticulum
What causes the lesions of bovine alimentary papilloma carcinoma to turn malignant?
Bracken fern
What type of cancer is bovine alimentary papilloma carcinoma?
Squamous cell carcinoma
Where in the body does enzootic haematuria affect?
The bladder
What causes enzootic haematuria?
Grazing on poor pastures with lots of bracken fern
What are the symptoms of enzootic haematuria?
Haemorrhaging from tumours in the bladder
What disease in horses is caused by papillomavirus?
Equine sarcoids
Which type of BPV is associated with equine sarcoids?
Type 1 or 2
What type of neoplasm is equine sarcoids?
Locally invasive benign fibroblastic skin/cutaneous tumour
How are equine sarcoids treated?
Surgical removal - recurrence is common
Can you vaccinate against equine sarcoids?
No
