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CVSOH BVSc3 > Virology - Orthomyxovirus and retroviruses > Flashcards

Virology - Orthomyxovirus and retroviruses Flashcards

1
Q

What are the main viruses in the orthomyxovirus family?

A

Influenza

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2
Q

What classification is orthomyxovirus genome?

A

Negative sense single stranded RNA

Group 5 of Baltimore classification system

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3
Q

Is orthomyxovirus enveloped?

A

Yes

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4
Q

What shape is orthomyxovirus?

A

Pleiomorphic - many different shapes

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5
Q

What is found in the lipid envelop of orthomyxovirus?

A

Peplomers - large glycoprotein spikes that protrude from the surface

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6
Q

What does having an lipid envelope cause in viruses?

A

Sensitivity to heat, acids

Are labile under normal environmental conditions

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7
Q

What symmetry does orthomyxovirus nucleocapsid have?

A

Helical

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8
Q

What are the two different types of cell surface peplomers in orthomyxovirus?

A

HA - haemagglutinin
NA - neuraminidase
Give the names eg. H1N1

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9
Q

What is haemagglutinin (HA) responsible for

on orthomyxovirus?

A

Attachment of virus to cells

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10
Q

What does neuraminidase do for orthomyxovirus?

A

Cleaves sialic acid from viral receptors glycoprotein so the virus can be released from the cell surface by budding

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11
Q

What activates haemagglutinin (HA) (in influenza viruses)?

A

Host cell proteases cleave it at its hinge region

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12
Q

What does HA1 bind to (in influenza viruses)?

A

Sialic acid

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13
Q

What does HA2 mediate (in influenza viruses)?

A

Membrane fusion

Fusion of the viral envelope with the endosomal membrane releasing viral contents into the cytoplasm

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14
Q

What type of sialic acid is found in mammalian respiratory tracts?

A

Galactose a-2,6 sialic acid

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15
Q

What type of sialic acid is found in wildfowl intestine?

A

Galactose a-2,3 sialic acid

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16
Q

Why is the type of sialic acid relevant (in influenza viruses)?

A

Some influenza viruses bind to one type better than the other

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17
Q

What type of sialic acid is found in pigs receptors?

A

Both a -2,3 and a-2,6 sialic acid expressed on their receptors
So pigs can catch both human and avian influenza
Mutations occur in pigs a lot as well

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18
Q

What type of influenza affects birds?

A

Influenza A - all subtypes

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19
Q

How many different haemagglutinin subtypes are there (in influenza viruses)?

A

18

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20
Q

How many different neuraminidase subtypes are there (in influenza viruses)?

A

11

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21
Q

What cell types are susceptible to influenza?

A

Ciliated columnar epithelium

Found in the respiratory tract

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22
Q

Where is ciliated columnar epithelium found?

A

Respiratory tract - sinuses, larynx, trachea, bronchi and bronchioles

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23
Q

How many segments of the influenza genome are there?

A

8

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24
Q

Which genome segments code for RNA polymerase (in influenza viruses)?

A

1,2,3

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25
Q

Which genome segment codes for haemagglutinin (in influenza viruses)?

A

4

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26
Q

Which genome segment codes for neuraminidase (in influenza viruses)?

A

6

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27
Q

How does influenza replicate its genome?

A

-ve sense RNA converted to +ve sense by RdRp

The +ve sense then makes viral proteins and is copied to make many -ve sense RNA which is then packaged

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28
Q

Where is RdRp found in influenza viruses?

A

Attached to the -ve sense RNA already

Cant make one bcos they are -ve sense not +ve sense

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29
Q

What triggers HA2 membrane fusion (in influenza viruses)?

A

Drop in pH in endosome

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30
Q

Where does genome replication/conversion to +ve sense RNA occur (in influenza viruses)?

A

Cell nucleus

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31
Q

What does antigenic drift cause changes to in influenza viruses?

A

The surface proteins haemagglutinin and neuraminidase

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32
Q

What does antigenic shift cause in influenza viruses?

A

Genome segments from two different viral strains are reassorted

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33
Q

Where does influenza virus assenbly and budding occur?

A

On the apical side of the epithelial layer - budding into the lumen of the airway

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34
Q

How does influenza virus enter the host?

A

Faecal oral route in birds
Small particles inhaled into lungs
Larger particles from coughs etc. into upper airways

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35
Q

How does influenza interfere with cell function?

A

Causes apoptosis

This causes inflammation, fever etc.

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36
Q

What causes more virulent strains of avian influenza?

A

Mutations causing cleavage of haemagglutinin in most tissues rather than just respiratory. This causes generalised infection as infectious virions can be released everywhere

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37
Q

What are the avian influenza designations and what determines them?

A

Low pathogenic avian influenza (LPAI)
Highly pathogenic avian influenza (HPAI)
The potential of the virus to kill chickens

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38
Q

What are tee main symptoms of highly pathogenic avian influenza?

A

Cyanosis
Bleeding from everywhere
Death

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39
Q

How do you diagnose avian influenza?

A

PCR assay to detect matrix protein gene
Then test for H5 and H7 genes
Then sequence to determine if there is enhanced cleavage

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40
Q

How do we control avian influenza?

A

Vaccination not permitted
Reporting, rapid action and culling
Surveillance

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41
Q

What are the symptoms of equine influenza?

A

High temperature
Nasal discharge
Dry cough

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42
Q

How is equine influenza spread?

A

Aerosols from coughing

Highly contagous

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43
Q

What are the two subtypes of equine influenza?

A

H3N8 and H7N7

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44
Q

How is equine influenza diagnosed?

A

PCR

Haemagglutination inhibition assay

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45
Q

How is equine influenza controlled?

A

Vaccination - inactivated with multiple different lineages

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46
Q

How is equine influenza treated?

A

No treatment, just supportive nursing care

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47
Q

What is the classification of retrovirus genome?

A

Positive strand RNA virus with DNA intermediate
Group 6 of the Baltimore classification system
The genome is diploid (the only one)

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48
Q

What enzyme is used by retroviruses?

A

Reverse transcriptase

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49
Q

What is an example of a retrovirus in humans?

A

HIV - AIDS

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50
Q

What are some conditions caused by retroviruses?

A

Inflammation
Neurodegeneration
Immunodeficiency
Cellular transformation

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51
Q

Do retroviruses have an envelope?

A

Yes

52
Q

What symmetry does the retrovirus nucleocapsid have?

A

Icosahedral

53
Q

What is found in the retrovirus capsid?

A

Two copies of the positive sense RNA - dimer

Reverse transcriptase - 30 molecules

54
Q

What does integrase do in retroviruses?

A

Helps integrate the converted double stranded viral genome into the host cell genome

55
Q

What does protease do in retroviruses?

A

Converts immature virions that are budding from the cell into mature, infectious virions
Cuts up the gag-pol polyproteins

56
Q

What does the relationship between envelope glycoproteins and host cell receptors mean in retroviruses?

A

The specific receptors responsible for virus attachment are unique to each retrovirus
This makes retroviruses species restricted

57
Q

What are the three major regions of the retrovirus genome?

A

Gag
Pol
Env

58
Q

What does the gag region of the retrovirus genome code for?

A

Structural proteins eg. capsid, matrix proteins

59
Q

What does the pol region of the retrovirus genome code for?

A

The enzymes eg. reverse transcriptase

60
Q

What does the env region of the retrovirus genome code for?

A

The peplomers - transmembrane glycoproteins

61
Q

What does the retrovirus genome have on its ends?

A

5’ cap

Poly A tail

62
Q

What does the reverse transcriptase enzyme have that allows it to produce double stranded DNA?

A

RdDp and DdDp (not RdRp, look closely)

So is a DNA polymerase that can copy either a DNA or an RNA template

63
Q

Where does DNA synthesis occur for retroviruses?

A

In the cytoplasm

64
Q

What is the hand domain of reverse transcriptase?

A

The part that grabs the viral genome

65
Q

What are the finger and thumb domains of reverse transcriptase?

A

The walls of the nucleic acid binding cleft

66
Q

What is the palm region of reverse transcriptase?

A

The base that contains the DNA polymerase active site

67
Q

What is a risk of reverse transcribing the retroviral genome?

A

It has no proofreading function

This causes a high error rate

68
Q

What part of the retrovirus gets deposited in the cytoplasm when it enters a host cell?

A

Only the capsid containing the genomic material

69
Q

Where does reverse transcription occur? Why?

A

Inside the capsid in the cytoplasm

Prevents DNA being degraded

70
Q

What is the term for when the double stranded DNA has been integrated into the host cell genome but is transcriptionally inactive?

A

Provirus

71
Q

What converts a provirus to a functioning retrovirus?

A

Host cell RNA polymerase starts transcribing it

72
Q

Where do retroviruses assemble?

A

On the inner surface of the plasma membrane

73
Q

What do budding retroviruses have?

A

An electron dense ring showing the gag pol polyproteins that are on the inner leaflet of the envelope

74
Q

What do mature retroviruses have?

A

A distinct conical structure inside the retrovirus

75
Q

What converts immature retroviruses to mautre retroviruses?

A

Protease

76
Q

What are oncogenes?

A

Genes that cause cancer

77
Q

How do retroviruses cause cancer? 3 ways

A

Contain stolen oncogenes in their genomes
Can stimulate overexpression of endogenous oncogenes
Can produce viral proteins that are oncogenic

78
Q

How may cancer cases have an infectious aetiology?

A

1 in 6

79
Q

What is the viral oncogene which causes the malignant changes induced by the Rous sarcoma virus?

A

v-src

80
Q

What is the v-src oncogene?

A

A tyrosine kinase which specifically phosphorylates tyrosine residues of critical cellular substrates in cells

81
Q

What does v-src cause?

A

Activation of oncogenic transduction pathways and therefore tumourgenesis

82
Q

What is the normal cellular counterpart of v-src?

A

c-src

Very similar to v-src but found in host cells

83
Q

What is different between v-src and c-src?

A

c-src is tightly regulated
v-src lacks 19 amino acids in the regulatory C terminal region of the genome
c-src is maintained in an inactive state, only activated by specific stimuli

84
Q

What are oncogenes required for and not required for by viruses?

A

Not required for virus replication

But are responsible for cellular transformation and development of cancer

85
Q

What is v-sis?

A

FeLv - growth factor that transforms fibroblasts into leukemia/sarcoma

86
Q

What is v-erb?

A

Avian leukosis virus - growth factor receptor

87
Q

What is v-fms?

A

Feline sarcoma virus - tyrosine phosphokinase

88
Q

What is v-myc?

A

Feline/avian leukaemia virus - nuclear transcription factor

89
Q

What is the name for viruses that contain oncogenes?

A

Acute transforming retroviruses

90
Q

What are acute transforming retroviruses?

A

Retroviruses containing oncogenes that integrate into the host genome and induce tumours rapidly

91
Q

What does a replication defective retrovirus mean?

A

Through obtaining an oncogene from the mammalian host, the retrovirus has lost an essential gene that controls the ability to replicate

92
Q

What is a replication competent retrovirus?

A

A retrovirus that can still replicate while containing an oncogene in its viral genome

93
Q

How do replication defective retroviruses replicate?

A

With the help of an endogenous retrovirus that can produce the proteins that its missing
Or if the cell is coinfected with another virus (helper virus) which can supply the proteins

94
Q

What is a non-acute retrovirus?

A

Induce tumours with a longer latency/over a long period of time

95
Q

What is a proto-oncogene?

A

Host cell genes that regulate cell growth eg. encode growth factors

96
Q

How do non-acute retroviruses cause tumours?

A

They cause insertional mutagenesis by influencing host cell proto-oncogenes with their powerful promoters on inserted proviruses which disrupts host cell growth regulation.
Also disrupt a tumour suppressor gene

97
Q

What are some examples of non-acute retroviruses?

A 
Avian leukosis virus
Murine leukaemia virus
Murine mammary tumour virus
Feline leukaemia virus
Non require a helper virus to replicate
98
Q

What is something else that can cause oncogenesis other than viral genome?

A

Viral regulatory proteins

99
Q

What spreads equine infectious anaemia?

A

Biting insects eg. horseflies, stable flies and mosquitoes

Also colostrum to foals

100
Q

How does equine infectious anaemia manifest?

A

Acute - fatal within a month
Chronic - 8-12 months
Inapparent carriers - after about a year

101
Q

What cells does equine infectious anaemia infect?

A

Monocytes and macrophages

102
Q

What organs/tissues does equine infectious anaemia infect?

A

Spleen
Liver
Tissues with lots of macrophages

103
Q

What are the clinical signs of equine infectious anaemia?

A

Fever - spike in virus causes a spike in fever
Anaemia
Thrombocytopenia
Wasting

104
Q

Hoe is it diagnosed?

A

Lots of testing
Coggins test
PCR

105
Q

What is the Coggins test?

A

Agar gel immunodiffusion test

Antibodies precipitate when bound to a capsid antigen

106
Q

Is there a vaccine for equine infectious anaemia?

A

In china, not in UK

107
Q

What is feline leukaemia virus?

A

An exogenous gamma retrovirus

108
Q

How is feline leukaemia virus transmitted?

A

Shed at mucosal sites

Transmitted via saliva or milk

109
Q

What disease syndromes are associated with feline leukaemia virus?

A 
Neoplastic disorders
bone marrow suppression
Neuro disorders
Immunodeficiency
etc.
110
Q

When can feline leukaemia virus cause oncogenesis?

A

When it integrates into the host genome in close proximity to cellular oncogenes c-myc

111
Q

What type of cancer is most common in feline leukaemia virus?

A

Lymphoma

112
Q

How do you diagnose feline leukaemia virus? What do you test for

A

PCR - detects provirus

Indirect immunofluorescence procedure o - detects p27 core protein

113
Q

Can you vaccinate against feline leukaemia virus?

A

Yes but they do not eliminate pre-existing infections

114
Q

How to prevent feline leukaemia virus?

A

It is a labile environment so disinfection can kill it

Regularly test cat colonies

115
Q

What does Jaagsiekte sheep retrovirus cause?

A

Infectious pulmonary adenocarcinomas

116
Q

How is Jaagsiekte sheep retrovirus spread?

A

As aerosolised pulmonary fluid between sheep in close contact

117
Q

What is the cellular receptor for Jaagsiekte sheep retrovirus?

A

Hyaluronidase 2 on many different types of cells

118
Q

What type of retrovirus is Jaagsiekte sheep retrovirus?

A

Simple retrovirus that doesnt contain a viral oncogene

119
Q

How does Jaagsiekte sheep retrovirus induce cellular transformation?

A

It produces a protein called Env protein that is responsible for oncogenesis

120
Q

What defines the Jaagsiekte sheep retrovirus tissue tropism?

A

The LTR region and the env gene product

121
Q

What is the retrovirus ligand for the hyaluronidase 2 receptor?

A

The env glycoprotein

122
Q

What are the two specific cell types that the retroviral LTR can work in?

A

Alveolar type 2 pneumocyres
Bronchiolar cells
So is confined to the lungs

123
Q

What time period does Jaagsiekte sheep retrovirus act in?

A

Lung tumours in as little as 10 days

124
Q

How do you diagnose Jaagsiekte sheep retrovirus?

A

ELISA

PCR

125
Q

Can you vaccinate against Jaagsiekte sheep retrovirus?

A

Nope

126
Q

How do you prevent Jaagsiekte sheep retrovirus?

A

Depopulation measures

Remove clinically infected sheep from flock

CVSOH BVSc3 (60 decks)

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