Veterinary Virology Flashcards
1
Q
Describe the properties of the nidoviruses.
A
Enveloped
Positive sense
RNA
Must replicate by generating negative sense RNA to make mRNA
2
Q
Name nidoviruses.
A
Alpha, beta and gamma coronaviruses
Porcine transmissible gastroenteritis virus
Feline coronavirus
3
Q
Describe the structure of coronaviruses.
A
Enveloped virus with characteristic large peplomers/spike protein and a core containing +RNA helical nucleocapsid.
4
Q
Describe the structure of coronavirus spikes.
A
It is a trimer – made up of 3 monomers, each with a S1 and 2 domain. Each of these has a receptor binding domain.
5
Q
How do coronaviruses enter cells?
A
Spike protein on the virion binds to ACE-2, a cell surface protein. TMPRSS2, an enzyme, help the virion enter via endocytosis.
6
Q
Describe the replication of coronaviruses.
A
- The virion releases it RNA into the cytoplasm.
- Some RNA is translated into proteins by the cells machinery, including the production of RdRp.
- Some of these proteins form a replication complex to make more RNA.
- Proteins and RNA are assembled into a new virion in the Golgi and released.
7
Q
What are syncytia?
A
Coronavirus can from syncytia - syncytia are multinucleated cells.
8
Q
How do coronaviruses form giant multinucleated cells?
A
Spike glycoprotein is expressed on the surface of the host cell and this might contribute to fusion with neighbouring uninfected cells by binding to its receptor via the ACE-2 of neighbouring cells.
9
Q
What is the purpose of coronavirus budding from the intracellular ER?
A
The virus does not have to kill the cell and can avoid exposing its peplomers on the cell surface where antibodies may bind and mediate complement fixation or ADCC. The virus is in circular intracellular vesicles.
10
Q
Describe the genome of coronaviruses.
A
Very large
Positive sense
5’ to 3’
6-7 genes
5’ cap
Poly A tail
11
Q
What is the purpose of a 5’ cap?
A
Protects the growing RNA chain from degradation by nucleases
12
Q
What is the purpose of a poly A tail?
A
Polyadenylation increases the stability of mRNAs. Plays a role in the initiation of translation promotes export from the nucleus.
13
Q
How is coronavirus genome replicated?
A
- RNA dependent RNA polymerase can only bind to RNA and undergoes polymerisation.
- The positive strand is first copied into a full length negative strand
- Negative strand is then copied into a full length + strand.
14
Q
How is porcine transmissible gastroenteritis virus transmitted?
A
Ingestion. The virus is acid labile and the virus is protected by milk and food as it passes through the stomach.
15
Q
How does TGEV enter cells?
A
Via attachment to receptor, aminopeptidase-N (APN), on epithelial cells on intestinal villi.
16
Q
What is the incubation period of TGEV?
A
18-72h
17
Q
What are the clinical signs of TGEV?
A
Vomiting
Profuse watery diarrhoea
Rapid weight loss
Dehydration
18
Q
What age group of pigs are most affected by TGEV?
A
Dangerous in neonatal populations of swine. Asymptomatic in adult pigs
19
Q
How does TGEV cause disease?
A
Destroys the integrity of intestinal architecture and disrupts intestinal homeostasis. Get severe blunting villus atrophy of villi. If these are damaged, affects the nutritional status of the animal.
20
Q
How can TGEV be diagnosed?
A
- Histological staining of intestines
- Antigen capture ELISA
- Isolate the virus from dead pigs, usually from kidneys, thyroid or testicle cells samples
- RT-PCR
21
Q
How can we protect against TGEV?
A
- Secretary IgA antibody is protective
- Vaccination of sows with live attenuated TGEV
- Depopulation and disinfection of affected pens
- Removal of Seropositive adults
22
Q
Name the 2 biotypes of feline coronavirus.
A
Feline infectious peritonitis virus/FIPV
Feline enteric coronavirus/FECV
23
Q
How is feline coronavirus transmitted?
A
Typically shed in faeces by healthy cats
Transmitted by the faecal-oral route
24
Q
How does FECV cause disease?
A
Infection of the mature gastrointestinal epithelial cells
25
What are the clinical signs of FECV?
Usually do not show any symptoms during the initial viral infection, but may occasionally experience brief bouts of diarrhoea and/or mild upper respiratory signs from which they recover spontaneously.
If the cat then develops FIP, the disease is progressive and almost always fatal
26
How does FIPV cause disease?
White blood cells becoming infected. An intense inflammatory reaction to FIPV occurs around vessels in the tissues where these infected cells locate, often in the abdomen, kidney, or brain.
27
Why do coronaviruses have a high level of genetic variation?
Due to the high error rate of RNA polymerase - leading to many different mutations in the virus genome
28
What do mutations in the coronavirus spike proteins allow FIPV to do?
Changes the viral cell tropism and allows FIPV to infect monocytes and macrophages. These cells can then get into the blood vessels and get transported around the cat’s body
29
What is antibody dependent enhancement of FIPV?
FIPV infects macrophages more easily in the presence of antibody. Antibodies raised against the spike protein can enhance infection – called Antibody Dependent Enhancement (ADE).
30
How are FECV and FIPV diagnosed?
- Histological examination - macrophages within lesions?
- ELISA does not distinguish FECV and FIPV
- Isolation of virus from nasal, oropharyngeal, and ocular swabs lung and trachea from necropsied cats. The virus can be propagated in cell cultures where viral cytopathic effect (plaque assay) is seen.
31
What are the properties of calicivirus?
Non-enveloped
Icosahedral symmetry
90 dimer capsomers
32 characteristic cup shaped depressions
Group 4 of BCS
32
Name 2 caliciviruses with human pathogens.
Norovirus
Sapovirus
33
Describe the calicivirus genome.
Linear
Positive sense
RNA
5' linked to viral genome linked protein/VPg
3' has poly A tail
34
What is the purpose of the VPg at the calicivirus 5' end?
- It protects the 5’ end of the viral RNA from cellular exonucleases that act in 5’ to 3’ manner
- VPg acts as a primer during –ve strand RNA synthesis. To replicate the RNA, the VPg interacts with RNA-dependent RNA polymerase (RdRp). This is called primer dependent replication.
35
How do caliciviruses attach to cells?
Carbohydrate attachment factors
36
How do caliciviruses enter host cells?
Dependent on Clathrin-mediated endocytosis.
37
What is calicivirus genome replicated?
Production of new positive strand RNAs from the negative strand RNA occurs. Subgenomic RNA is also formed during genome replication.
38
How does calicivirus assemble?
The genomic RNA, and in some cases the subgenomic, is encapsidated possibly with the help of VP2.
39
What are JAM-A junction proteins?
Expressed at junctions between calls, which is where virus binds and enters the cells. Viral capsid protein VP1 binds to JAM-A on target cells to enter.
40
Why do caliciviruses not bud off?
Non-enveloped
41
What conditions are caused by feline calicivirus?
Oral ulcers
Gingivitis
Nasal ulcers
Nasal discharge
Febrile lameness
42
How is feline calicivirus transmitted?
Mainly by fomites, direct contact between cats, and occasionally over short distances by aerosol. The virus also can be passively carried to susceptible cats by human handlers.
43
What are the clinical signs of feline calicivirus?
- Starts in the oropharynx, extends to URT and eyes
- Initial short incubation period (2-5days)
- Fever
- Mild rhinitis
- Sneezing
- Nasal discharge
- Conjunctivitis
- Palatine ulcerations
- In some cases there is bronchopneumonia
- Footpad lesions
44
How is feline calicivirus diagnosed?
- Nasal, oropharyngeal, and ocular swabs, lung and trachea from necropsied cats
- PCR
- Isolation and identification of virus
45
Is vaccination available for feline calicivirus?
Live attenuated intramuscular vaccines are available but not suitable for pregnant cats.
46
What is RHD?
Rabbit Haemorrhagic Disease Virus (RHDV), a calicivirus
47
How is RHDV transmitted?
Faecal-oral route, biting insects, flies and fomites
48
What is the pathology of RHD?
Nasal haemorrhage
Necorosis of liver
DIC
49
How is RHDV diagnosed?
Immunofluorescence or immunohistochemical staining
RT-PCR
ELISA
50
Is there a vaccine for RHDV?
Vaccines to control the disease have been prepared as an inactivated homogenate of infected rabbit tissue mixed with adjuvant.
51
What are the properties of flaviviruses?
Positive sense
Single stranded RNA
Icosahedral capsid
Tight lipid envelope
Group 4 BCS
52
How can flavivirus and pestivirus be distinguished?
50nm = flavivirus
40-60nm = pestivirus
53
How do flaviviruses enter the body?
Deposited into the skin epidermis by a mosquito/tick bite where they encounter cells permissive to infection such as keratinocytes and skin dendritic cells
54
How do flaviviruses cause disease?
Dendritic cells migrate to lymphoid organs > circulation > internal organs.
Many are neuroinvasive and neurovirulent and cause central nervous system damage
55
How do flavivirus and pestivirus genomes differ?
Flavivirus capped but not polyadenylated
Pestivirus genome is not capped and not polyadenylated
56
What does flavivirus sfRNA do?
Dampen antiviral processes in cells
57
Which flaviviruses forms are infectious?
Mosaic and immature are not infectious, only mature and fully cleaved are infectious.
58
How does a flavivirus become infectious?
prM proteins is associated with E protein, which is kept in a non-fusogenic state by prM (furin cleaves prM to M, making virus infectious).
59
How is Louping ill (flavi)virus transmitted?
Ixodes Ricinus
60
How does Louping ill cause disease?
Replication at site of entry in macrophages and dendritic cells > local lymph nodes > pperipheral tissues > primary fever associated with IFN-a response and viraemia > lymphoid organs and continues to replicate > prolonged viraemia > secondary fever
61
What are the clinical signs if Louping ill?
- Sheep develop a febrile response and cccompanying neurological signs
- Ataxia
- Fine muscular tremor
- Hyperexcitability
- Incoordination
- Convulsions
- Rapid onset of coma and death
62
What is the difference between Louping ill in sheep and in cattle?
Some sheep recover. In cattle, is more protracted
63
How is Louping ill diagnosed?
- History of neurological signs
- Histological detection of non-suppurative encephalomyelitis (inflammation of brain)
- Culture of brain specimens in tissue culture or embryonated eggs to grow virus
- RT-PCR
- Detection of IgM antibodies
- Haemagglutination inhibition
64
What is bovine viral diarrhoea virus?
A pestivirus. Can be either cytopathic or non-cytopathic.
- Cytopathic – kills cells in tissue culture, arises from a virus mutation
- Non-cytopathic – does not change cells in culture, most common biotype in nature
65
Describe the 2 biotypes of BVD?
Biotype 1 = conversion to cytopathic form causes typical mucosal disease
Biotype 2 = non-cytopathic. But conversion to cytopathic from causes thrombocytopenia and haemorrhagic disease
66
What are the clinical signs of BVD?
Most infections are subclinical
Inappetence, depression, fever, diarrhoea.
67
When does persistent infection of BVD occur?
90-120 day of gestation - non-cytopathic strain. Virus infects foetuses before immune competence, immune tolerance to the virus occurs = PI animals.
68
How does BVD result in embryonic death?
Transplacental spread to the foetus within 30 days of gestation
69
What happens if there is BVD infection between 30 and 90 days of gestation?
Mummification, abortion, congenital abnormalities of the CNS.
70
What does infection of BVD after 120 days gestation result in?
Foetus infection after 120 days of gestation can mount an adaptive immune response and are normal at birth.
71
What are the clinical signs of mucosal disease caused by BVD?
Depression
Fever
Profuse watery diarrhoea
Nasal discharge
Salivation
Lameness
Ulcerative lesions (mouth and interdigital cleft)
72
What is the structure of reoviruses?
Icosahedral
Non-enveloped
Triple layered capsid
Segmented genome (9-12 segments)
Double stranded RNA
73
Describe the reovirus genome.
Double stranded DNA
Segments can be large, medium or small
5' cap
No poly A tail
74
Why are there numerous serotypes and strains of reoviruses?
Genetic reassortment readily takes place in cells coinfected with viruses of the same species (genetic shift). There is a high mutation rate (genetic drift).
75
How do reoviruses enter cells?
- σ1 carbohydrates
- Junctional adhesion molecule-A (JAM-A)
- Lambda 2 (base of σ1) to bind β1 integrin on cells
- Enter by receptor-mediated endocytosis
76
What is rotavirus?
A reovirus
Main causative agent of childhood diarrhoea
7 serogroups
77
How is rotavirus transmitted?
Contact and by the oral/faecal route
78
What are the clinical signs of roatvirus?
Vomiting
Anorexia
Depression
Profuse, watery diarrhoea of sudden onset, which quickly results in extreme dehydration
79
How does rotavirus cause disease?
Predominantly infects mature enterocytes at the middle and top of intestinal villi, with prominent vacuolization. Damaged villi become short, resulting in reduced nutrient adsorption.
80
What is bluetongue virus?
Reovirus spread via biting midges vector
81
How does bluetongue virus cause disease?
Midges chews through skin and ruptures blood vessels > sucks up pool of blood > virus in circulation > interacts with blood cells > vascular thrombosis, infarction, necrosis and haemorrhage
82
What are the clinical signs of bluetongue virus?
Most sheep and cattle do not develop clinical signs. Some animals experience:
- Fever
- Loss of appetite
- Conjunctivitis
- Hyperaemia of mucus membranes
- Drooling
- Lameness
- Pulmonary oedema
- Respiratory distress
- Cyanosis (blue tongue)
- Lameness and hyperaemia of the coronary band
83
How does bluetongue virus cause death?
Due to pulmonary oedema – results from primarily congestion of the lungs caused by the accumulation of fluid and massive internal haemorrhaging.
84
What is required for bluetongue virus transmission?
Takes 2 waves of feeding for transmission
85
What are the properties of retroviruses?
Positive strand
RNA with DNA intermediate
Group 6 BCS
86
How are retroviruses endogenous?
In humans, endogenous retroviruses occupy about 8% of the genome
87
Describe the retrovirus genome.
Diploid genome
Positive sense
Single stranded RNA
3' poly A tail
5' cap
Encodes reverse transcriptase and integrase enzymes
88
How is the retrovirus genome replicated?
The Reverse transcriptase (RT) enzyme has both RNA dependent DNA polymerase (RdDp) and DNA dependent DNA polymerase activity (DdDp). By a complex series of steps, it makes a complete double stranded DNA copy of the virus genome. Integrase put double stranded viral DNA into host genome. Host polymerases then make viral transcripts.
89
What is the role of reverse trasncriptase in retrovirus replication?
Reverse transcriptase synthesises cDNA within the capsid. Several copies of virus cDNA are integrated into host genome at “random” loci through the actions of viral integrase enzyme, forming a provirus.
90
How are mature and immature retroviruses?
Immature (without capsid core) and mature forms (with capsid core). Mature can only cause disease as they have capsid, unlike immature that do not so they are not protected in the cell.
91
What is viral latency?
A state whereby the virus is dormant – not actively replicating. This duration of inactivity is variable and unpredictable.
92
What are retroviral oncogenes?
1 in 6 cancers worldwide have an infectious aetiology. Some retroviruses:
- Contain captured oncogenes in their genomes
- Can stimulate overexpression of endogenous oncogenes
- Produce viral proteins that are oncogenic
93
Describe oncogene capture.
1. Extra gene src in oncogenic virus compared to a typical retrovirus been captured from host cell.
2. Src is a tyrosine-protein kinase – phosphorylates tyrosine residues on itself and cell encoded proteins.
3. The viral src gene (v-src) is derived from a cellular gene, c-src, that is highly conserved.
4. The v-src is mutationally activated via reverse transcription induced mutations, compared to c-src gene.
5. Elevated levels of activity of Src promotes cell survival and growth.
94
How is Rous sarcoma virus an exception to onco-carrying retroviruses?
The defective viruses can replicate only with the help of an endogenous retrovirus, or in a cell co-infected with a helper virus
95
How can retroviruses without oncogenes induce oncogenic mutations?
Insertional mutagenesis:
- Provirus integrates in regions in or near regions encoding oncogenes
- Through this integration, the oncogene can be activated because the elements the virus brings with it can enhance or disrupt normal transcription
96
How do acute and non-acute transforming retroviruses differ?
Unlike acute transforming retroviruses, these non-acute transforming retroviruses do not require a helper virus to replicate.
97
Name 2 retroviruses that result in cancerous aetiologies.
Feline leukaemia virus
Jaagsiekte sheep retrovirus/pulmonary carcinoma virus
98
What is FLV?
An exogenous gamma-retrovirus that causes a variety of often debilitating disease syndromes in infected domestic cats.
99
List 6 FLV-associated disease syndromes.
Neoplastic disorders
Bone marrow suppression
Neurologic disorders
Immunodeficiency
Immune mediated diseases
Stomatitis
100
When does FLV cause neoplasia?
When it integrates in close proximity to cellular oncogenes such as c-myc
100
When is FLV diagnosed?
- Commercial ELISA kits are available for practitioners.
- PCR can be used to detect the virus genome.
- An indirect fluorescence antibody procedure (IFA) on blood smears
101
How is FLV prevented?
Easily inactivated by disinfectants.
Cats in colonies can be regularly tested for FLV by ELISA and infected cats removed.
102
What is Jaagsiekte sheep retrovirus/pulmonary carcinoma virus?
Affects sheep (frequent) and goats (less frequent). Causes infectious pulmonary adenocarcinomas.
103
How is Jaagsiekte sheep virus transmitted?
Horizontally between sheep that are in close contact by aerosolised pulmonary fluid.
104
Does Jaagsiekte sheep virus contain oncogenes?
Jaagsiekte sheep retrovirus is a simple retrovirus that does not include a viral oncogene. Instead, the virus’ Env protein is the inducer of cellular transformation and creates pulmonary adenocarcinomas.
105
How does Jaagsiekte sheep virus induce lung tumours?
Alveolar type II pneumocytes, and bronchiolar cells, thereby defining the highly restricted tissue tropism of this virus. JSRV can induce lung tumours in as little as 10 days.
106
How is Jaagsiekte sheep virus diagnosed?
- Clinical specimen: formalin-fixed lung tissue, preferably with a lesion
- ELISA and PCR on pulmonary fluids
107
How is Jaagsiekte sheep virus prevented?
Vaccines not available. Clinically affected sheep should be removed from the flock.
108
What are orthomyxoviridae?
Contains those viruses that cause influenza in humans. BCS group 5
109
What is the structure of orthomyxoviruses?
Pleomorphic
8 helical nucleocapsids, 8 segments each with RdRp bound
Negative sense RNA
Haemagglutinin and neurominidase
110
What is the function of orthomyxovirus haemagglutinin?
Acidification of endosomes allows HA-2 to mediate membrane fusion and viral RNA to become deposited in the cytoplasm.
111
What are the orthomyxovirus influenza virus receptors?
Galactose a-2-6 sialic acid – mammalian respiratory tract
Galactose a-2-3 sialic acid – wildfowl intestine.
112
How do human and avian influenza differ?
Human influenza virus = alpha (2,6) linkage
Avian influenza virus = alpha(2,3) linkage
113
Why can pigs be infected with both human and avian influenza viruses as 'mixing vessels'?
Epithelial cells of the pig trachea produce high amounts of both alpha (2,3) and alpha (2,6)-linked sialic acids expressing receptors.
114
Where in the respiratory tract are influenza viruses found?
Influenza viruses infect the ciliated columnar epithelium found in the sinuses, nasopharynx, larynx, trachea, bronchi and bronchioles.
115
Where do orthomyxoviruses replicate?
In the nucleus, 1 of 2 viruses that does this
116
Describe antigenic drift in influenza viruses.
When mutations in the genes of influenza viruses occur, leading to changes in the surface proteins of the virus – this can cause the mutated virus to have higher infectivity or better able to evade immune responses. RdRp is responsible for drift as it is error prone during genomic replication.
117
Describe antigenic shift in influenza viruses.
Whole genome segments of IAV, between 2 different viral strains are reassorted to make a chimeric virus. This occurs during coinfection of a single host cell. This is infrequent. These are huge and sudden changes in the viral genome composition and often leads to pandemics.
118
How do orthomyxoviruses enter the host according to particle size?
Small particles 1-3um diffuse deep into the lung tissue by a number of mechanisms including diffusion, sedimentation and electrostatic effects.
Large particles over 6um impact further up the respiratory tract due to their weight, depositing in a size dependent manner from the nasal passages to the larger bronchioles.
119
What cells do orthomyxovirus influenza viruses target?
Ciliated epithelial cells lining the respiratory tract with budding predominantly occurring on the luminal side.
120
How do orthomyxovirus influenza viruses alter cell function?
Apoptosis, necrosis, necroptosis, possibly pyroptosis
121
How do orthomyxovirus influenza viruses cause disease?
Inflammation, cytokine and interferon production sickness behaviour, fever, increased mucous secretion, sensitisation of nociceptors, pain, sneezing, coughing
122
What are the clinical signs of low pathogenicity avian influenza?
- Sneezing
- Coughing
- Ocular discharge
- Nasal discharge
- Swollen infraorbital sinuses
- Sinusitis
- Congestion and inflammation of the trachea and lungs
- Decreased egg production
- Morbidity and mortality is low
123
What are the clinical signs of high pathogenicity avian influenza?
- Severe systemic disease
- Cyanosis of the comb and wattle
- Oedema of head, face and neck
- Haemorrhages on visceral organs
- Blood in oral and nasal discharges
- Diarrhoea
- Lacrimation
- High mortality in chickens and turkeys
- Sinusitis
124
How is avian influenza controlled?
The vaccination of poultry and captive birds not currently permitted.
Early reporting, rapid action, culling and surveillance remain the most effective ways of protecting against and controlling an avian influenza outbreak.
125
What are the clinical signs of equine influenza?
High temperature
Nasal discharge
Dry cough
Depressed
Loss of appetite
126
Describe the vaccination against equine influenza.
Inactivated vaccines containing 2 different lineages of H3N8 viruses, preferably including strains that match the prevalent field virus are used. Several vaccinations are necessary to achieve full protection of individual horses. Annual boosters are required thereafter.
127
How is equine influenza treated?
There is no specific treatment for horses with equine influenza. Many horses needing mostly supportive and nursing care. Sometimes there is a secondary bacterial infection which can need further treatment.
128
What are the properties of rhabdovirus?
Group 5 BCS
Large peplomer envelope
5 proteins
400 trimers glycoprotein in membrane
129
Describe the rhabdovirus genome.
Helically symmetrical nucleocapsid
Negative sense
Single stranded
RNA
130
Name a rhabdovirus.
Lyssavirus, causing rabies
131
How is rhabdovirus genome replicated?
RNA > mRNA via RNA dependent RNA polymerases
The genome is also the template for the synthesis of full-length positive sense strands, which in turn are copied to produce negative sense strand genomes.
132
How do rhabdoviruses enter the host cells?
n-acteylcholine receptor (nACHR) on muscle cells and NCAM and p75NTR on neurons. Gangliosides may also participate.
Receptor mediated endocytosis
133
How does rabies virus bud off in replication?
Occurs principally from intracytoplasmic membranes of infected neurons
134
How does rabies cause neurological signs?
1. Replication at site of entry or direct infection of nerves
2. Transported along the axon to the nerve cell body where further replication takes place
3. Spinal cord and on to the CNS
4. Infection of the limbic system
135
Why is the most likely transmission of rabies via saliva?
Spread centripetally to salivary gland via parasympathetic nerves. In the salivary glands, the virus bud from the cell membrane into the salivary ducts.
136
What are the 2 phases of neurological symptoms of rabies?
Excitive (furious) phase – cats, dogs, horses
The paralytic (dumb) phase – cattle
137
What are the clinical signs shared by both phases of rabies?
Restless
Aggressive
Unable to swallow
Salivation
Hyperaesthesia
138
How is rabies diagnosed?
- Direct immunofluorescence or immunohistochemical staining of brain tissue
- RT-PCR assay of brain tissue
139
Which vaccines are available for rabies?
Inactivated, live-attenuated and recombinant vaccines have been developed for the parenteral immunization of animals and humans against rabies.
Successful oral vaccination against rabies has been achieved using either live-attenuated or recombinant vaccines that are delivered in baits to target wildlife species.
140
What is the structure of papillomavirus?
Spherical
Non-enveloped
Icosahedral symmetry
Viral coat contains 360 molecules of L1 protein, variable number of L2
141
What is the genome of papillomavirus?
Group 1 BCS
Supercoiled double stranded DNA
Histones
142
What are the early and late proteins of papillomavirus?
Early proteins E1-8 are non-structural
Late proteins L1-L2 are structural and make up the virus capsid.
143
How are E1 and E2 proteins involved in papillomavirus replication?
E1 is a helicase that binds and unwinds the DNA to allow access of the cellular replicative machinery.
E2 is a helicase loader and helps E1 bind to the replication origin (Ori).
144
Where is papillomavirus replicated?
Nucleus
145
What is the role of protein E5 in papillomavirus pathology?
- Binds to phosphorylates and activates PDGF-R: causing constitutive growth signalling
- Interacts with 16kDuctin/subunit C disrupting gap junction signalling
- Alters endosomal pH causing MHC retention in Golgi
146
What is the role of p53 protein in papillomavirus pathology?
p53 is a host cell transcription factor activated in response to cell stress. p53 induces apoptosis of virally infected cells.
147
What is the role of protein E6 in papillomavirus pathology?
Localized in the nucleus and promotes the destruction of p53 tumour suppressor, preventing apoptosis.
148
What is the role of p105RB protein in papillomavirus pathology?
A host cell suppressor protein that binds to the transcription factor E2f. The binding of p105Rb prevents E2f from transcribing genes associated with the cell cycle
149
What is the role of protein E7 in papillomavirus pathology?
Localized in the nucleus and interacts with p105Rb, liberating the host cell transcription factor E2f. This results in cell cycle activation and proliferation that is not controlled.
150
What does papillomavirus cause?
Warts
151
What is bovine alimentary papilloma-carcinoma?
Causes papillomas of the oesophagus, rumen and reticulum. The lesions are small.
Ingestion of bracken fern facilitates papilloma progression to invasive carcinoma of the alimentary tract. Lesions can lead to difficulty in swallowing, ruminal tympany and loss of condition.
152
What is enzootic haematuria?
Cattle grazing on poor pstures with lots of bracken fern. Haemorrhaging comes from tumours in the bladder.
153
What are equine sarcoids?
Locally invasive fibroblastic skin tumours of head, ventral abdomen and limbs. Associated with BPV type 1 or 2. Surgical removal. Reoccurrence common
154
What are the properties of the paramyxoviruses?
- Group 5 BCS
- Initiate infection in the respiratory tract
- Measles and mumps disseminate through the body while replication limited to respiratory epithelium.
- Pleomorphic
- Lipid envelope
155
Describe the paramyxovirus genome.
Helically symmetrical nucleocapsid
Single stranded RNA
Negative sense
156
Which proteins are associated with paramyxovirus?
Haemagglutinin
Neurominidase
Fusion protein
Polymerase
157
What complex is formed during paramyxovirus replication?
RdRp is a complex of the L protein and P protein. Together the L, P bind the N protein to form the Ribonucleoprotein complex (RNP).
158
When do paramyxoviruses cause mild and severe disease?
Most transmit through the airborne route and infect epithelial cells of the airway using sialic acid as a receptor. Most only cause mild disease. Some can cross the epithelial barrier and cause more severe disease.
159
What is the function of the F protein of paramyxoviruses?
Mediate fusion of neighbouring cells to from syncytia.
160
What is the paramyxovirus, canine distempter virus/morbillivirus?
Associated with multiple cell tropism – epithelial, lymphoid and neurological. Leads to systemic infection – respiratory, digestive, urinary, lymphatic, cutaneous, skeletal, CNS
161
How does canine distemper virus enter cells?
SLAM/CD150
nectin-4
162
Give the time line and process of canine distemper virus pathology.
Day 1 – aerosol infection of tonsils
24-48 hours – infection of lymph nodes
Day 4-6 – primary transient viraemia pyrexia spread to lymphoid organs, cough
Day 8-10 – secondary viraemia and pyrexia, infection of non-lymphocytes by cell fusion. Gastroenteritis, pneumonia, catarrhal secretions
Day 20-60 – de-myelinating viral encephalitis. Tremors, convulsions, death
163
What are the clinical signs of canine distemper virus 1 week after initial contact with the virus?
Reddened eyes
Nasal and eye discharge
High fever
Lethargy
Loss of appetite
Cough
Diarrhoea and vomiting
164
What are the clinical signs at later stages of canine distemper virus?
Neuromuscular tics
Seizures
Hyperkeratosis
165
How is canine distemper virus diagnosed?
- Clinical signs
- Blood and urine tests and skin biopsies
- RT-PCR
- ELISA tests for CVD specific IgM
- Electron microscopy for virus in faecal preparations
- Haemagglutination inhibition using serum
- Post mortem stain of lymph nodes, urinary tract, bladder and cerebellum
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Name the 2 vaccines for canine distemper virus.
Modified-Live CDV Vaccines
Heterotypic (Measles) Virus Vaccination
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What is Rinderpest?
A notifiable disease, a paramyxovirus
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How can rinderpest be transmitted?
Can be transmitted through consumption of contaminated water, direct contact or aerosolised body fluids over short distances
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What are the clinical signs of rinderpest?
Ulcerating sores in the soft
Extreme fevers
Loss of appetite
Diarrhoea
Weakness
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What are the properties of parvovirus?
Non-enveloped
Icosahedral symmetry
Group 2 BCS
60 proteins in capsid
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Describe the parvovirus genome.
Linear
Single stranded
DNA
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How is parvovirus fairly stable in the environment?
Stable to lipid solvents and pH ranges 3-9, can be inactivated by bleach, formalin and oxidising agents.
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What are the functions of NS1 proteins to parvovirus?
- Binds to DNA and is required for viral DNA replication
- Serves as a helicase
- Serves as an endonuclease
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What is the function of NS2 proteins to parvovirus?
Regulates viral gene expression
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What is the function of VP1 protein to parvovirus?
Less frequent protein that makes up the viral capsid (10%)
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What is the function of VP2 protein to parvovirus?
Predominant protein that makes up the viral capsid (90%)
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How is the parvovirus genome replicated?
RNA can be made only from a dsDNA template so some DNA synthesis must precede mRNA production in the replication cycles. The virus requires host DNA replication machinery for replication of the viral DNA, as the virus does not encode or package a DNA polymerase. Cellular DNA polymerases replicate the viral DNA to form a double-stranded DNA intermediate, used as a template for mRNA.
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How is canine parvovirus transmitted?
Shed in the faeces
Ingestion or inhalation, transmission occurs by direct and indirect contact (fomites).
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What is the timeline of infection for canine parvovirus?
1. 3-7 day incubation period
2. Replicate in lymph nodes.
3. 2 days later, virus released into blood stream
4. Over the next 3-4 days, the virus disseminates to organs where cells rapidly divide (bone marrow, intestine)
5. The virus can also attack the heart in young dogs leading to inflammation of heart muscle, poor function, and arrhythmias.
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How does canine parvovirus cause disease?
Kills villi crypt cells. Villi become blunted and unable to absorb nutrients and diarrhoea results. The epithelial barrier function breaks down. The diarrhoea becomes bloody and bacteria can enter the body causing widespread infection. Diarrhoea and vomiting = extreme fluid loss and dehydration = shock and death
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How is canine parvovirus diagnosed?
- Haemagglutination
- PCR
- Virus isolation in cell culture
- Antigen capture ELISA
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What does porcine parvovirus infection cause?
Stillbirths, mummification, embryonic death, infertility
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How are gilts protected from porcine parvovirus?
Gilts are at risk as maternal antibody may protect from infection until 1st pregnancy established. Control by vaccination of gilts or by deliberate infection
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What are the properties of adenovirus?
Group 1 BCS
Non-enveloped
Icosahedron
Fibre at each vertex
15 structural proteins
Capsid made of hexons and pentons
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Describe the adenovirus genome.
Non-segmented, linear double stranded DNA
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What are early and late adenovirus proteins?
Most early proteins are involved in regulating transcription
The late proteins are structural
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How is the adenovirus replicated?
- In the nucleus
- Transcribed by cellular RNA polymerase DdRp
- Double stranded DNA synthesis uses viral DNA polymerase, E2 encoded
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When are adenoviruses infectious?
Virus capsids can be empty (non-infectious) or contain the complete viral genome (infectious).
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What is canine adenovirus 1?
Causes infectious canine hepatitis and respiratory or ocular disease
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How is canine adenovirus transmitted?
Transmission via ingestion of urine, faeces or saliva from infected animals.
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What is the peracute syndrome of canine adenovirus 1?
Pup is found dead either without apparent preceding illness or after an illness lasting only 3 or 4 hours.
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What is the acute syndrome of canine adenovirus 1?
Which may be fatal, marked by fever, depression, loss of appetite, vomiting, bloody diarrhea, petechial hemorrhages of the gums, pale mucous membranes.
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What is the mild syndrome of canine adenovirus 1?
Might be a vaccine-modified disease— that is, the result of partial immunity.
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What are the clinical signs of canine adenovirus 1?
Fever
Apathy
Anorexia
Thirst
Conjunctivitis
Serous discharge from the eyes and nose
Occasionally abdominal pain
Tachycardia
Leukopenia
Disseminated intravascular coagulation
Blue eye
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What is canine adenovirus 2?
Causes a localised respiratory disease in dogs and is a potential cause of the kennel cough syndrome. Respiratory disease in affected dogs is characterized principally by bronchitis and bronchiolitis.
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What is an essential difference between canine adenovirus 1 and 2?
Canine adenovirus 1 causes systemic disease, canine adenovirus 2 infection results only in restricted respiratory disease. Spread is mainly by direct and indirect contact.
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What are poxviruses?
Large DNA viruses that can infect vertebrates and invertebrates and form pox lesions on the skin. Group 1 BCS
198
Describe the structure of poxviruses.
- Pleomorphic but typically brick shaped
- Irregular surface of tubular or globular structures
- Core contains the viral genome (DNA)
- Virions are released from the cell by budding and not cellular disruption, therefore their membranes contain cellular proteins
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How are parapoxviruses different to poxviruses?
- Ovoid and not brick shaped
- Regular surface – covered with long thread-like structures that appear criss-crossed
200
Describe the poxvirus genome.
Linear, double stranded DNA. Crosslinking at terminal loops occurring ta tandem repeats.
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What regions can the poxvirus genome be divided into?
Regions that encode structural proteins and essential enzymes for replication are clustered in the centre of the genome
Regions that affect virulence, host range, or immunomodulation are predominantly near the ends
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How do poxvirus viroreceptors evade host immune responses?
Not anchored to the cell membrane (so they get secreted). The receptor depletes their ligand from the environment preventing signalling. Disrupts IFN activity and TNF activity.
203
How do poxvirus virokines evade the host immune response?
Disrupt cytokine, chemokine and complement activity.
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How are poxviruses transmitted?
Skin abrasions
Contaminated environment
Aerosol
Biting arthropods
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Which poxvirus species have narrow host ranges?
Camelpox and variola virus
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Which poxvirus species have wide host range?
Cowpox virus and monkeypox virus
207
How is swinepox transmitted?
most commonly between swine by the bite of the pig/hog louse, Hematopinus suis.
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How does vaccinia virus attach to host cells?
Outer membrane proteins, D8, A27, H3 and A26, bind to cell surface glycosaminoglycans and thereby facilitate virion attachment.
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Which inclusion bodies do poxviruses produce?
Acidic inclusion bodies – proteinaceous mass containing virus
Basic inclusion bodies – nucleic acid rich areas of virus replication
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What is the pathogenesis of poxviruses?
1. Macule red flat spot on epithelium
2. Papules caused by oedema and cellular proliferation
3. Formation of vesicles
4. Pustules form as vesicles rupture and ooze serum
5. Able to survive long periods in environment – years. Survive particularly well in desiccated scab material
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What is the severe form of buffalopox?
Disease is characterized by pustular lesions on the teats and udders of milking buffalo. Lesions also can occur at the base of the ear and in the inguinal region.
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What is the severe form of buffalopox virus?
Rare, and lesions are more generalized.
213
What is cowpox?
A rodent virus which may spread to cows, cats, humans and zoo animals. Bank voles and wood mice are the reservoir
214
What is feline cowpox?
Necrotizing dermatitis. Recovery in 6-8 weeks. Infection can become generalised with widespread skin lesions macules progressing to papules then ulcerating and forming pustules with secondary bacterial infection.
215
What is orf?
Contagious ecthyma/contagious pustular dermatitis virus. Papules progressing to pustules then develop thick crusty scabs. Severely affected animals may lose weight and be predisposed to secondary infections
216
How is orf spread?
Direct contact
Mechanical vectors
217
What are 2 forms of bovine parapoxvirus?
Pseudocowpox virus
Bovine popular stomatitis
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What is pseudocowpox virus?
Characterized by bright red papules, followed by vesicles, scabs, and nodules on the udder and teats of cows
219
How is pseudocowpox virus controlled?
Spread is horizontal so hygienic milking practices help control
220
What is bovine popular stomatitis?
Mild disease with reddish, raised papules that may ulcerate on the epithelium of the mouth, muzzle and in the nostrils. Less severe than Orf in sheep.
221
How is bovine popular stomatitis controlled?
Transmission is by direct contact and fomites so hygienic milking practices.
222
What are herpesviruses?
Large, enveloped viruses
Group 1 BCS
Alpha, beta or gamma herpesviruses
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Describe the genome of herpesviruses.
Linear, double stranded DNA
Icosahedral nucleocapsid
Genome divided into short and long regions
Each U region is flanked by inverted repeats
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What are the properties of alpha herpesviruses?
- Short replication cycle, less than 24 hours
- Variable host range
- Rapid destruction of cultured cells
- Establish latent infections in neuronal cells
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What are the properties of beta herpesvirses?
- Long replication cycle, greater than 24h
- Narrow host range
- Slow destruction of cultured cells
- Cytoplasmic and nuclear inclusions
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What are the properties of gamma herpesviruses?
- Narrow host range
- Lymphotropic
- Establish latency in lymphocytes
- Cytolytic infection in epithelial
- Cells and fibroblasts
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How is the herpesvirus genome replicated?
- DNA enters nucleus as a linear molecule and converts to circle
- DNA replicates from circle
228
Describe the 3 categories of proteins encoded by herpesviruses.
- Alpha (immediate early) and beta (early) proteins are generally enzymes and DNA binding proteins
- The gamma (late) proteins are structural proteins.
229
How do herpesviruses enter host cells?
Binding to glycosaminoglycans
Fusion or endocytosis
230
Describe how herpesviruses can be latent.
Primarily maintained in host cells in a circular episomal (extrachromosomal) form or, less often, through chromosomal integration. The latent genome is essentially silent and persist for the lifetime of the host.
231
What is the role of herpesvirus genes not essential for viral replication?
Their role is to influence host cell functions and regulate the immune response via protective immunity and viral immune evasion.
232
What is bovine herpesvirus 1?
Bovine rhinotracheitis and infectious pustular vulvovaginitis/balanpothesis.
233
What are the clinical signs of bovine herpes virus 1?
Fever
Serous nasal discharge
Gastroenteritis
Cough
Conjunctivitis, often profuse lacrimation
Discharge becoming purulent with epithelial ulceration
Abortion
Generalised disease death
Encephalitis in calves
234
What is pustular vuvlovaginitis?
- Fever
- Depression
- Anorexia
- Stand apart, often with the tail held away from contact with the vulva
- Vulval labia are often swollen and there is a slight vulval discharge
235
What are the main latency sites of bovine herpes 1?
The sciatic = following genital disease
Trigeminal ganglia = following respiratory disease
236
What is mammillitus caused by bovine herpes virus 2?
Lesions restricted to the teats and udder. Arthropod vector and through milkers and milking machines
237
What is pseudo-lumpy skin disease caused bovine herpes virus 2?
Symptoms include fever and skin nodules on the face, back, and perineum. The disease heals within a few weeks. Spread via biting insects.
238
What does bovine herpes virus 4 cause?
Endometritis, vulvovaginitis, associated abortion and mastitis.
Latency, often residing in the trigeminal ganglia.
239
What is caused by bovine herpes virus 5?
Meningoencephalitis and respiratory disease with recrudescence at times of stress and/or immunosuppression. Lesions initially occur in the midbrain and later involve the entire brain.
240
How does bovine herpesvirus 5 spread?
From the nasal cavity, pharynx, and tonsils via the maxillary and mandibular branches of the trigeminal nerve.
241
What is caused by feline herpesvirus 1?
Fever
Nasal discharge
Salivation
Keratitis/corneal ulcers
Severe rhinotracheitis bronchitis and pneumonia in kittens
242
How is feline herpesvirus 1 spread?
Discharge from an infected cat’s eyes, mouth or nose
