Flashcards
Rhabdo/papillomavirus
Cards in this deck (68)
- 1What is the structure of the Rhabdovirus?ss –ve sense RNA, enveloped
- 2What virus causes Rabies?Lyssavirus genus
- 3What are general properties of the Rabies virus?o Can affect all mammals with wide variation in clinical signs
o A major public health issue at a global level
o Spreads via nerves to the Central Nervous System (CNS); phosphoprotein blocks interferon; excreted in saliva.
o Causes behavioural changes: Furious rabies or Dumb rabies
o Confirmation of diagnosis usually at post-mortem (Negri bodies)
o Vaccination is available - 4What species is a major transmitter of Rabies and can be found in the UK?Bat - Lyssavirus
- 5What order does the Rhabdoviridae family belong to?Mononegravirales
- 6Give 3 diseases that can be found in the Rhabdoviridae family.- Rabies
- Vesicular Stomatitis virus
- Bovine Ephemeral Fever virus - 7What is the structure of the rabies virus genome?- Single strand of –ve sense RNA, which is bound to a nucleoprotein and
wound up into a helix
- Helically symmetrical nucleocapsid is
enclosed in a lipid envelope containing glycoprotein peplomers - 8What is the shape of the rabies virus?Short rods or bullets
- 9What is the genome structure of typical Rhabdovirus?Le - Leader
N - nucleoprotein binds to RNA to form capsid
P - blocks interferon induction and response
M - binds nucleocapsid to envelope glycoprotein
G - envelope glycoprotein
L - RNA polymerase - 10What is found for each gene and why?- There is a single promotor each gene has a stop start codon.
- The viral polymerase starts at the three prime end and transcribes each gene in turn. Because only a proportion of transcriptases move on there is more RNA from 3’ than 5’ genes. - 11What is made later in replication and why?Full length +RNA transcript which serves as a template for genomic -RNA
- 12Why is the nucleocapsid self assembling?It is attached by the viral M protein to sites of G protein insertion in membranes
- 13What must the virus carry to be able to replicate itself?RNA polymerase as it is -ve sense and so needs to make +ve sense RNA to be able to be read by host ribosomes
- 14How are new virus particles produced?Budding from a cell membrane, the location of the budding varies with the cell type in which the virus is growing
- 15What species can be infected by rabies?All mammals
- widespread differences in susceptibility of species to infection, as well as virus strain variations in host preference - 16Is rabies a human health concern?Yes! Zoonotic
- 17How is rabies usually spread?- By saliva following a bite from an infected
animal; therefore carnivores tend to be the most important hosts
- Some cases reported following mucosal exposure or inhalation - 18What happens following exposure?- Prolonged incubation period of 14-90 days (7 years in one human case)
- 19What is the rabies virus pathogenesis?- Infects locally and binds to cells via acetylcholine receptor or to gangliosides
- Initial infection of muscle and replication at site of entry or direct infection of nerves
- Once neurones have become infected the virus is transported by centrifugal axioplasmic flow along the axon to the
nerve cell body where replication takes place
- Replication/infection occurs along nerves
- Passes through spinal cord and on to the CNS and then to the brain
- Infection of lymbic system causes rabies symptoms - 20Is the rabies virus pathogenic to the nerve cell?No - buds mainly from the endoplasmic reticulum, leading to a build up of virus particles within vacuoles in the cell
- 21How does the rabies virus spread?Not fully understood
- Fusion of adjacent nerve cell membranes or exocytosis of virus then fusion to neighbouring cells are possible routes of spread - 22What has been associated with increased pathogenicity?Certain key amino acid residues within the virus G-protein and mediating cell membrane fusion
- 23Does the virus kill the nerve cells and what is the advantage of this?No
Remaining largely hidden within the nerves the virus invokes little inflammation or immune response and its phosphoprotein (P) acts to block interferon - 24What are the clinical symptoms of rabies?- Behavioural changes including disorientation, loss of fear of humans, roaming abroad in daylight, aggression hyperexcitability = FURIOUS RABIES
- Salivation, unable to swallow, hyperaethesia, weakness = Dumb rabies - 25What happens when the virus spreads to the neocortex?Increasing weakness progressing to paralysis and death
- 100% mortality - 26Why is salivation and swallowing issues symptoms of rabies?Spread centripetally along neurones to various organs most notably the salivary glands where virus replication is rapid and budding takes place from the cell surface leading to large concentrations of virus in the salivary secretions
- Pharyngeal paralysis - 27When is transmission most likely?When it has spread centripetally to a variety of organs including salivary glands
- 28How can you diagnose rabies?- Demonstration of virus in brain at post mortem
- Negri Bodies in purkinje cells = low sensitivity
- Immuno-fluorescence of impression smear
- PCR is now used for speed and sensitivity - 29What is immunity of rabies?- Little immune response in clinical cases where infection has been within the nerves
- Lack of response is important for pathogenicity of virus
- P protein to block interferon response, preventing inflammation and consequent opening of the BBB to admit lymphocytes into the CNS. - 30What has been used to engineer a rabies virus with deletion of P protein which can still be grown in cell culture and can infect mice?Reverse genetics
- 31What does the engineered virus cause on infection?- Inflammation and T-cell invasion of the CNS
- An encephalitis associated with these viruses, which enables the immune system to clear the virus and the mice to recover.
- Deletion mutant is given to a mouse infected with wild type virus both viruses are cleared by the immune response and clinical disease does not develop - 32What should happen if an animal is suspected of having rabies?- Captured and observed for developing signs
- 33What is the pre-exposure vaccination?- (Inactivated ) wild type rabies virus - highly immunogenic when used as a vaccine
- Current vaccine strains are grown in
cell culture or eggs and inactivated before being administered as an intramuscular injection
- Virus neutralising antibodies induced by vaccination are protective - 34Are all dogs required to be vaccinated?Yes if travelling
- 35What has pre-exposure vaccination lead to?Breaks the transmission link from wild animals to Humans therefore only people at high risk of contacting rabid animals are vaccinated routinely
- 36What is the post-exposure treatment?Immunisation: Vaccination following exposure - but prior to symptoms- can be effective in preventing disease onset.
- Wound should be cleaned (lipid envelope - deactivate)
- Immune serum given both locally and systemically
- (for humans, humanised monoclonal antibodies are available but expensive).
- Active immunisation with inactivated cell culture virus started at this time.
- Cheaper form of vaccine can be made directly from formalin treated brain tissue as large amount of virus antigen present, however a large volume of tissue must be injected on several occasions.
- This is given by intraperitoneal injection and the side effects are severe. - 37What are the different reservoirs of rabies found worldwide in wild animal populations?- European rabies = Foxes
- North America: Skunk, Arctic fox, Racoon, Coyote
-> Each associated with distinct strains of virus
- South America = Vampire Bats
- In most countries transmission to humans is via infection of domestic dogs and cats. - 38What must happen to all vaccinated dogs?Micro-chipped
- 39What are the vaccines available?- Cell culture adapted rabies strains purified virus, inactivated plus adjuvant
- Live Recombinant expressing rabies glycoprotein G (vaccinia virus, canarypox, ORF) - 40What's been used to help to reduce the incidence of rabies in the fox population in Europe?- Vaccination of wild foxes by bait containing recombinant live vaccinia has been highly successful in Europe.
- Elimination of foxes does not work and provides a population boom of susceptible foxes. - 41What is the problem with Bat rabies?Many varieties of Lyssavirus that are carried by bats and may cause Rabies like diseases in other animal
- 42What are the forms of bat rabies that can be found?Rabies worldwide
Mokola virus (Central Africa)
Lagos Bat virus
Duvenhague (South africa)
European Bat Lyssavirus 1 and 2,
Australian Bat lyssavirus , and
Unexplained Rabies cases in US found to
be virus of Bat origin - 43What is the structure of the Papillomavirus?dsDNA, non-enveloped icosahedral capsid
- 44How is the Papillomavirus spread?Spread by contact, cause proliferative lesions of epithelial cells and keratinocytes
- 45What is the problem with Bovine papillomavirs and it's 6 types?- Cause fibropapillomas (often cutaneous but also bladder and GI – note association with malignant transformation following bracken ingestions “enzootic haematuria”)
- Implicated in equine sarcoids - 46What do Papillomavirus cause?Benign proliferative lesions of some epithelial cells and keratinocytes in the basal dermis and stratum spinosum of the skin - in all species
- 47How are papillomaviruses spread and infect?- Very stable in the environment
- Spread by direct or indirect contact and
- Infect susceptible hosts (usually young animals) through small lesions in the skin or epithelial membranes. - 48What happens after adhesion and endocytosis?Virus un-coats and its DNA is transported to the nucleus were it is maintained as a separate circular episome
- 49What is the virus genome divided into?Early and late regions
- Only early expressed in basal layers of skin - 50What does the interaction of the genome cause?- Host cell proteins as well host cell DNA.
- Alter the transcription and function of several proteins that regulate the growth pattern of the infected cells
- Infected cells divide more rapidly at each division.
- Virus genome is replicated expanding the number of infected cells.
- Infected cells differentiate into keratinised skin or mature epithelial cells synthesis of the late (structural) virus proteins begins
- New virus particles assemble within the
nucleus (in the upper stratum spinosum) and are released when the cells die and are sloughed off. - 51What is pathology of Papillomavirus due to?BPV E5, E6 and E7 which have number of actions affecting cell growth and differentiation
- 52What is the replication of papillomavirus related to?Replication is intimately related to the proliferations and differentiation of their host epithelial or skin cells
- 53What can be used to demonstrate the virus particles in the keratinised layer?Electron microscopy
- 54What does the restriction of the host species do for the papillomavirus?Lesions they cause most often regress after several months in association with a host immune response.
- 55What can be used to detect papillomavirus in normal skin?PCR
- 56How are dogs affected by papillomavirus?- Canine papillomavirus (CPv1-13)
- Multiple Oral Papillomas around the
lips and gums, oropharynx,(usually regress)
- Also pigmented skin plaques, some tumours - 57Are cats affected by papillomavirus?Increasingly becoming recognised as causing skin lesions and cancers in cats
- 58How are horses effected by the papillomavirus?- EcPV1 Papillomas on the face young horses (regress spontaneously)
- EcPV2 Genital warts usually persist.
- EcPV3 Aural plaques usually persist - 59What are the 6 types of bovine papillomavirus?Type 1/2: Fibropapillomas on skin of young cattle and Sarcoids in horses
Type 3: cutaneous papillomas cattle
Type 4: papillomas of the alimentary tract (malignant)
Type 5: fibropapillomas on the teats
Type 6: papillomas on the teats - 60What is the problem with type 4 bovine papillomavirus?- Lining of the rumen and reticulum can transformed to malignant carcinomas when animals are grazing on Bracken.
- The virus acts to create a pre-neoplastic environment were the mutagenic toxins found in bracken can act to promote the progression of the lesion to complete neoplasia. - 61What happens with type 2?Similar aetiology is ascribed to enzootic haematuria, where immune-suppression
due to grazing bracken allows reactivation of latent BPV type-2 lesions in the bladder with further transformation of the lesion again due to toxins in bracken. - 62What are equine sarcoids?•Associated with BPV type 1 or type 2 DNA
•Equine specific sub-types of E2 and L2 proteins
•Four different types of lesion: Fibropapilloma, Verrucose, Occult and Peri-occular/nodular.
•Genetic / breed susceptibility
•Express early gene products.
•May progress to neoplastic lesion - 63What gene products have been detected by immunohistology for equine sarcoids?E2, E5, E6, E7
- 64What happens to infected horses with equine sarcoids?- Affected horses do not seroconvert to virus
- Late (structural) proteins were thought to be absent
- Some evidence shows late virus protein present (occasionally)
- Are affected horses immuno-tolerant to the virus?
- Virus evasion strategy ? No interferon response
- Retention of MHC I in golgi - 65What are cells infiltrated with?- Extensive CD4 CD8 T-cells
- Extensive FoxP 3 expression - both within T-cells (regulatory) and tumour cells - 66Why is the papillomavirus persistent in sarcoids?•Sarcoids do not usually regress spontaneously
•Poor induction of interferon by BPV infected equine cells.
•No Immune response to late proteins.
•Immunity to early proteins unknown.
•Certain MHC haplotypes predispose to
infection (poor antigen presentation)
•Down-regulation of MHCI surface expression by BPV E5. - 67What is thought to be a vector of sarcoid?Facefly - musca autumnalis
- 68What is the treatment for sarcoids?- Surgical Treatment (may recur)
- Immunotherapy: BCG injected into lesions
and
- Autogenous vaccines made from sarcoid tissue
- Cytotoxic creams (many different types)
- Therapeutic vaccination?
Combined VLP/E7 vaccine : variable success
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- Animal Disease 2 (Specific Viruses - DW) Flashcards on Rhabdo/papillomavirus, created by Rachael Jones on 29/11/2017.
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- Rachael Jones
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