Respiratory Viruses Flashcards

1
Q

What are modes of respiratory virus transmission?

A
  • Direct contact
  • Airborne transmission: Aerosol or droplet
  • Contaminated fomites e.g. surfaces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the characteristics of a droplet?

A

Over 5 micrometers
Transmission distance <1 metre
Can remain airborne for hours
Deposited mainly on mucous membranes and the upper respiratory tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the characteristics of an aerosol?

A

Less than 5 micrometers in size
Transmission distance <1 metre
Can remain airborne indefinitely
Deposited mainly on the lower respiratory tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which viruses are capable of spreading via the respiratory route but are not capable of causing respiratory disease?

A
Measles
Mumps
Rubella
Chicken pox- varicella zoster virus
Small pox- variola virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which viruses are capable of respiratory disease?

A
Coronaviruses: MERS, SARS
Adenoviruses
Influenza viruses
Rhinoviruses
Parainfluenza
Respiratory Syncytial Virus= RSV
Human metapneumovirus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Measles is capable of transmission via?

A

The respiratory route

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which human virus is the most contagious?

A

Measles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What glycoproteins are present on the surface of measles?

A

Fusion

Hemagglutinin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What receptors can measles use to enter cells?

A

CD46
SLAM
Nectin-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

SLAM?

A

Signalling lymphocyte activation molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

SLAM receptor is located on?

A

Immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can measles infect individuals?

A

Airborne transmissible
Enters and can bind to the SLAM receptor located on dendritic cells
Transported to the lymph and the blood where there are more lymphocytes expressing SLAM which measles can infect more lymphocytes and immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the R0 of measles?

A

12-18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the entry receptor for measles?

A

SLAM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the exit receptor for measles?

A

Nectin-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does measles exit occur?

A

Binding to the Nectin-4 exit receptor which is present on the basal side of the airway epithelium. Enters the epithelial cell, can undergo a round of replication and can be expelled where it can transmit to other individuals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the entry receptor of measles?

A

SLAM

Signalling lymphocyte activation molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the exit receptor of measles?

A

Nectin-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Measles genome?

A

-ssRNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Measles baltimore?

A

Group V

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Measles order?

A

Mononegavirales

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Measles has a high R0 of?

A

12-18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Rhinovirus order?

A

Picornavirales

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Rhinovirus family?

A

Picornaviridae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Rhinovirus genus?

A

Enterovirus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Other members of the enterovirus include?

A

Poliovirus

Coxsackievirus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Genome of rhinovirus?

A

+ssRNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Baltimore classification of rhinovirus?

A

IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Rhinovirus causes?

A

The common cold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Rhinovirus genome structure?

A

+ssRNA
Attached to VPg protein at the 5’ end
5’ IRES which allows CAP independent translation
Genome encodes a polyprotein which can be post-translationally cleaved into individual proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What proteins does the genome encode for?

A

Structural and non-structural proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

First the genome is cleaved into?

A

P1, P2 and P3
P1 encodes the structural proteins
P2 and P3 encode the non-structural proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

P1 can be further processed into which proteins?

A

VP0, VP1 and VP3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

VP0 structure?

A

N myristoylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How is VP0 N’ myristoylated?

A

By the host cell N’-myrisotyltransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the function of N’-myristoylated VP0?

A

Important in capsid assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the most common disease affecting mankind?

A

The common cold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How many years of someone’s life is spend with a cold?

A

2-3 years of a person’s life is spent with a cold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Rhinovirus capsid structure?

A

Made up of structural proteins: VP1, VP2, VP3 and VP4
VP1,2,3 are found on the outer capsid. They form protomers, 5 protomers form a pentamer and 12 pentamers are required to make the icosahedral capsid
VP4 is localised within the capsid where it binds to the +ssRNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Which structural proteins account for the antigenic diversity of rhinoviruses?

A

VP1, VP2 and VP3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

When is VP0 cleaved to form VP2 and VP4?

A

During maturation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What does VP1 form?

A

VP1 forms a star-shaped plateau on the five-fold axis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What surrounds the star-shaped dome/plateau of VP1?

A

A deep canyon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Where does the host cell receptor bind?

A

Usually bind in the canyon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What can be found within the canyon?

A

A hydrophobic pocket, containing the pocket factor lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What is the importance of the pocket factor lipid?

A

To stabilise the virion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Upon receptor binding what happens to the pocket factor lipid?

A

It is released and the capsid destabilises

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Where is the pocket factor lipid originally from?

A

It is host cell derived

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Mimicking the pocket factor lipid is a potential?

A

Drug target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

If the pocket factor is not released?

A

Destabilisation of the capsid cannot occur

Cell invasion cannot occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Why do we catch influenza yearly?

A

We catch influenza yearly due to the antigenic drift which occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Do we catch the common cold annually due to antigenic drift?

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Why do we catch the common cold annually?

A

As there are around 160 serotypes of the common cold co-circulating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

The 160 serotypes of rhinovirus can be divided into which three groups?

A

Groups: A, B and C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

The groups A and B use which receptors for entry?

A

Either VLDL or ICAM-1 receptor

56
Q

Rhinoviruses which bind to the VLDL receptor are which group?

A

The minor group rhinoviruses

57
Q

Rhinoviruses which bind to the ICAM-1 receptor are which group?

A

The major group rhinoviruses

58
Q

Group C rhinoviruses are distinct and bind which receptor?

A

Bind the cadherin receptor: CDHR3

59
Q

CDHR3 is the receptor that which group of rhinoviruses binds to?

A

Group C rhinoviruses

60
Q

VLDL stands for?

A

Very-low-density-lipoprotein

61
Q

Which groups of rhinoviruses bind to either VLDL or ICAM-1 receptors?

A

Group A and B rhinoviruses

62
Q

Where does the ICAM-1 receptor bind the rhinovirus?

A

Binds the rhinovirus in the deep canyon which surrounds the star shaped plateau of VP1 on the 5 fold axis

63
Q

Where does the VLDL bind the rhinovirus?

A

The star shaped plateau/dome.

64
Q

ICAM-1 stands for?

A

Intracellular adhesion molecule 1

65
Q

What is the normal function of ICAM-1?

A

To allow extravasation of lymphocytes
Located on the surface of endothelial cells
Binds to integrin LFA-1 and allows lymphocyte extravasation

66
Q

In areas of inflammation the level of?

A

ICAM-1 increases

67
Q

Therefore areas of inflammation?

A

Facilitate rhinovirus entry

68
Q

What is Rossman’s canyon hypothesis?

A

The hypothesis is that the function of the canyon is to evade immune recognition. The canyon is small enough to allow the receptor to bind but too small to allow antibodies access to the conserved regions. The receptor binding site needs to be invariant and therefore it is necessary to shield it from the immune system. The parts of the virion that are exposed e.g. on the plateau are free to develop mutations etc…

69
Q

Why is there no rhinovirus vaccine, even though there is a poliovaccine?

A

A vaccine would only protect against a single serotype as the serotypes are antigenically distinct. Therefore you would need to be successfully immunised against all 160 serotypes to prevent getting the common cold. We have yet to identify any clear conserved epitopes that can be targeted.

70
Q

What are two possible drug targets of rhinovirus?

A
  • A drug to mimic the pocket factor lipid

- A drug to inhibit the action of cellular N’-myristoyltransferase

71
Q

Rhinovirus C can cause issues in individuals with?

A

Asthma

72
Q

What can rhinovirus C do to those with asthma?

A

It can exacerbate the asthma

73
Q

Rhinovirus C binds to which cellular receptor?

A

CDHR3

74
Q

CDHR3 is what type of receptor?

A

It is a cadherin receptor

75
Q

CDHR3 is used by which rhinovirus group for cell entry?

A

Group C rhinoviruses

76
Q

What are the two forms of CDHR3?

A

Tyrosine at 529

Cysteine at 529

77
Q

Which form of CDHR3 is the most common today?

A

The cysteine at position 529

78
Q

What is the ancestral form of CDHR3?

A

The tyrosine at position 529

79
Q

CDHR3 comes in which two forms?

A

Tyrosine at position 529

Cysteine at position 529

80
Q

What is the difference between the two forms of CDHR3?

A

Do not differ in protein synthesis or mRNA expression

They differ in their cell surface expression

81
Q

Which form of CDHR3 is expressed higher at the cell surface?

A

Tyrosine form of CDHR3

82
Q

Which form of CDHR3 is expressed at lower levels at the cell surface?

A

Cysteine form of CDHR3

83
Q

Why is it believed that the cysteine form is more common nowadays?

A

Believed it has been selected for to protect us from the consequences of asthma exacerbations associated with the tyrosine form

84
Q

Most individuals hospitalised with rhinovirus C have which CDHR3 variant?

A

The ancestral tyrosine CDHR3 variant

85
Q

Why is rhinovirus C often referred to as a new virus?

A

Newly discovered but it has been around for ~8000 years

We could not propagate it in cell culture as the cells did not express CDHR3

86
Q

Human cysteine Cys-529 CDHR3 variant protects from?

A

Expressed at lower levels on the cell surface

Protects from the rhinovirus C exacerbations

87
Q

What is the drug (potential rhinovirus treatment) developed at Imperial College London known as?

A

Imp-1088

88
Q

Imp-1088 does what?

A

It is an enzymatic inhibitor of cellular N’-myrisoyltransferase

89
Q

Imp-1088 inhibits N’-myrisoyltransferase which causes?

A

It prevents N’ myristoylation of VP0 which prevents capsid assembly

90
Q

Is Imp-1088 toxic?

A

Shown not to be toxic to humans

91
Q

How would Imp-1088 be prescribed?

A

Either prophylactically but preferably just as someone notices symptoms of rhinovirus infection

92
Q

RSV virus belongs to which order?

A

Mononegavirales

93
Q

Genome of RSV?

A

-ssRNA

Group V

94
Q

By what age will most humans be infected by RSV?

A

Age 3

95
Q

RSV can cause some severe complications such as?

A

Bronchiolitis

96
Q

What is the leading cause of hospitalisation in children under 5 years of age?

A

RSV

97
Q

How does RSV enter cells?

A

Via the fusion protein

98
Q

What is the function of NS2?

A

NS2 causes the cytopathic effects

NS2 is associated with the cytopathicity of the virus

99
Q

What can NS2 cause?

A

It can cause morphological changes, loss of cilia and airway clogging

100
Q

What was the main issue surrounding the formalin-inactivated vaccine?

A

This vaccine caused the symptoms of RSV to be worse

It exacerbated the infection

101
Q

Why did the formalin-inactivated vaccine exacerbate the RSV disease?

A

It caused antibodies to be formed against the post-fusion F protein rather than the pre-fusion F protein. Neutralising antibodies able to prevent cell infection will be required against the pre-fusion F. The antibodies against the post-fusion F did not prevent infection but did lead to complement activation and worse symptoms

102
Q

As a result of the vaccine how many children died?

A

Two toddlers died

103
Q

Most children are infected with RSV at what age?

A

2-3 months

104
Q

What are children mostly infected with between 6-12 months?

A

Human metapneumovirus

105
Q

Human metapneumovirus genome and classification?

A

Mononegavirales order
-ssRNA
Group V

106
Q

the second most common cause after human respiratory syncytial virus (RSV) of lower respiratory infection in young children IS?

A

Human metapneumovirus

107
Q

Coronavirus family?

A

Cornaviridae

108
Q

Coronavirus genome?

A

+ssRNA

109
Q

Cornavirus baltimore classification?

A

IV

110
Q

Human coronavirus causes?

A

Colds

111
Q

What are two examples of zoonotic coronaviruses?

A

SARS

MERS

112
Q

SARS stands for?

A

Severe Acute Respiratory Syndrome

113
Q

MERS stands for?

A

Middle Eastern Respiratory Syndrome

114
Q

When was the SARS outbreak?

A

2003

115
Q

Where did the SARS outbreak begin?

A

Southern China

116
Q

When was the MERS outbreak?

A

2012

117
Q

Where did the MERS outbreak begin?

A

Saudi Arabia

118
Q

Animal reservoir of SARS?

A

Cave dwelling horseshoe bats

119
Q

Animal reservoir of MERS?

A

Camels

120
Q

When did SARS disappear?

A

2004

121
Q

Why was SARS easier to control than a future influenza pandemic?

A

People are only infective once they begin displaying symptoms. Contrastingly, individuals infected with influenza can shed virus before they develop symptoms

122
Q

MERS and SARS can both lead to the development of?

A

Pneumonia

123
Q

What is the receptor for MERS?

A

DPP4 receptor

124
Q

What is the DPP4 receptor?

A

Dipeptidyl peptidase 4

125
Q

DPP4 stands for?

A

Dipeptidyl peptidase 4

126
Q

Where is DPP4 present in humans?

A

In the lower respiratory tract

On the alveolar epithelial cells

127
Q

Where is DPP4 present in camels?

A

In the upper respiratory tract

128
Q

Why is MERS not easily transmissible from human-to-human?

A

As the DPP4 are located on the alveolar epithelial cells, a prerequisite required for human-to-human transmission is the replication in the upper respiratory tract where the virus can be easily spread

129
Q

Adenovirus genome?

A

dsDNA

Group I

130
Q

What is an emerging adenovirus?

A

HAdV-55

131
Q

Which countries has HAdV-55 infection been seen in?

A

Turkey, China, Korea, Spain

132
Q

HAdV-55 was first observed in?

A

China

133
Q

HAdV-55 is associated with which places?

A

Military camps

134
Q

HAdV-55 is often?

A

Sporadic and random

135
Q

What complications does it cause?

A

Severe pneumonia