Respiratory Viruses Flashcards
(135 cards)
1
Q
What are modes of respiratory virus transmission?
A
- Direct contact
- Airborne transmission: Aerosol or droplet
- Contaminated fomites e.g. surfaces
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
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
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
5
Q
Which viruses are capable of respiratory disease?
A
Coronaviruses: MERS, SARS Adenoviruses Influenza viruses Rhinoviruses Parainfluenza Respiratory Syncytial Virus= RSV Human metapneumovirus
6
Q
Measles is capable of transmission via?
A
The respiratory route
7
Q
Which human virus is the most contagious?
A
Measles
8
Q
What glycoproteins are present on the surface of measles?
A
Fusion
Hemagglutinin
9
Q
What receptors can measles use to enter cells?
A
CD46
SLAM
Nectin-4
10
Q
SLAM?
A
Signalling lymphocyte activation molecule
11
Q
SLAM receptor is located on?
A
Immune cells
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
13
Q
What is the R0 of measles?
A
12-18
14
Q
What is the entry receptor for measles?
A
SLAM
15
Q
What is the exit receptor for measles?
A
Nectin-4
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
17
Q
What is the entry receptor of measles?
A
SLAM
Signalling lymphocyte activation molecules
18
Q
What is the exit receptor of measles?
A
Nectin-4
19
Q
Measles genome?
A
-ssRNA
20
Q
Measles baltimore?
A
Group V
21
Q
Measles order?
A
Mononegavirales
22
Q
Measles has a high R0 of?
A
12-18
23
Q
Rhinovirus order?
A
Picornavirales
24
Q
Rhinovirus family?
A
Picornaviridae
25
Rhinovirus genus?
Enterovirus
26
Other members of the enterovirus include?
Poliovirus
| Coxsackievirus
27
Genome of rhinovirus?
+ssRNA
28
Baltimore classification of rhinovirus?
IV
29
Rhinovirus causes?
The common cold
30
Rhinovirus genome structure?
+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
31
What proteins does the genome encode for?
Structural and non-structural proteins
32
First the genome is cleaved into?
P1, P2 and P3
P1 encodes the structural proteins
P2 and P3 encode the non-structural proteins
33
P1 can be further processed into which proteins?
VP0, VP1 and VP3
34
VP0 structure?
N myristoylated
35
How is VP0 N' myristoylated?
By the host cell N'-myrisotyltransferase
36
What is the function of N'-myristoylated VP0?
Important in capsid assembly
37
What is the most common disease affecting mankind?
The common cold
38
How many years of someone's life is spend with a cold?
2-3 years of a person's life is spent with a cold
39
Rhinovirus capsid structure?
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
40
Which structural proteins account for the antigenic diversity of rhinoviruses?
VP1, VP2 and VP3
41
When is VP0 cleaved to form VP2 and VP4?
During maturation
42
What does VP1 form?
VP1 forms a star-shaped plateau on the five-fold axis
43
What surrounds the star-shaped dome/plateau of VP1?
A deep canyon
44
Where does the host cell receptor bind?
Usually bind in the canyon
45
What can be found within the canyon?
A hydrophobic pocket, containing the pocket factor lipid
46
What is the importance of the pocket factor lipid?
To stabilise the virion
47
Upon receptor binding what happens to the pocket factor lipid?
It is released and the capsid destabilises
48
Where is the pocket factor lipid originally from?
It is host cell derived
49
Mimicking the pocket factor lipid is a potential?
Drug target
50
If the pocket factor is not released?
Destabilisation of the capsid cannot occur
| Cell invasion cannot occur
51
Why do we catch influenza yearly?
We catch influenza yearly due to the antigenic drift which occurs
52
Do we catch the common cold annually due to antigenic drift?
No
53
Why do we catch the common cold annually?
As there are around 160 serotypes of the common cold co-circulating
54
The 160 serotypes of rhinovirus can be divided into which three groups?
Groups: A, B and C
55
The groups A and B use which receptors for entry?
Either VLDL or ICAM-1 receptor
56
Rhinoviruses which bind to the VLDL receptor are which group?
The minor group rhinoviruses
57
Rhinoviruses which bind to the ICAM-1 receptor are which group?
The major group rhinoviruses
58
Group C rhinoviruses are distinct and bind which receptor?
Bind the cadherin receptor: CDHR3
59
CDHR3 is the receptor that which group of rhinoviruses binds to?
Group C rhinoviruses
60
VLDL stands for?
Very-low-density-lipoprotein
61
Which groups of rhinoviruses bind to either VLDL or ICAM-1 receptors?
Group A and B rhinoviruses
62
Where does the ICAM-1 receptor bind the rhinovirus?
Binds the rhinovirus in the deep canyon which surrounds the star shaped plateau of VP1 on the 5 fold axis
63
Where does the VLDL bind the rhinovirus?
The star shaped plateau/dome.
64
ICAM-1 stands for?
Intracellular adhesion molecule 1
65
What is the normal function of ICAM-1?
To allow extravasation of lymphocytes
Located on the surface of endothelial cells
Binds to integrin LFA-1 and allows lymphocyte extravasation
66
In areas of inflammation the level of?
ICAM-1 increases
67
Therefore areas of inflammation?
Facilitate rhinovirus entry
68
What is Rossman's canyon hypothesis?
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
Why is there no rhinovirus vaccine, even though there is a poliovaccine?
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
What are two possible drug targets of rhinovirus?
- A drug to mimic the pocket factor lipid
| - A drug to inhibit the action of cellular N'-myristoyltransferase
71
Rhinovirus C can cause issues in individuals with?
Asthma
72
What can rhinovirus C do to those with asthma?
It can exacerbate the asthma
73
Rhinovirus C binds to which cellular receptor?
CDHR3
74
CDHR3 is what type of receptor?
It is a cadherin receptor
75
CDHR3 is used by which rhinovirus group for cell entry?
Group C rhinoviruses
76
What are the two forms of CDHR3?
Tyrosine at 529
| Cysteine at 529
77
Which form of CDHR3 is the most common today?
The cysteine at position 529
78
What is the ancestral form of CDHR3?
The tyrosine at position 529
79
CDHR3 comes in which two forms?
Tyrosine at position 529
| Cysteine at position 529
80
What is the difference between the two forms of CDHR3?
Do not differ in protein synthesis or mRNA expression
| They differ in their cell surface expression
81
Which form of CDHR3 is expressed higher at the cell surface?
Tyrosine form of CDHR3
82
Which form of CDHR3 is expressed at lower levels at the cell surface?
Cysteine form of CDHR3
83
Why is it believed that the cysteine form is more common nowadays?
Believed it has been selected for to protect us from the consequences of asthma exacerbations associated with the tyrosine form
84
Most individuals hospitalised with rhinovirus C have which CDHR3 variant?
The ancestral tyrosine CDHR3 variant
85
Why is rhinovirus C often referred to as a new virus?
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
Human cysteine Cys-529 CDHR3 variant protects from?
Expressed at lower levels on the cell surface
| Protects from the rhinovirus C exacerbations
87
What is the drug (potential rhinovirus treatment) developed at Imperial College London known as?
Imp-1088
88
Imp-1088 does what?
It is an enzymatic inhibitor of cellular N'-myrisoyltransferase
89
Imp-1088 inhibits N'-myrisoyltransferase which causes?
It prevents N' myristoylation of VP0 which prevents capsid assembly
90
Is Imp-1088 toxic?
Shown not to be toxic to humans
91
How would Imp-1088 be prescribed?
Either prophylactically but preferably just as someone notices symptoms of rhinovirus infection
92
RSV virus belongs to which order?
Mononegavirales
93
Genome of RSV?
-ssRNA
| Group V
94
By what age will most humans be infected by RSV?
Age 3
95
RSV can cause some severe complications such as?
Bronchiolitis
96
What is the leading cause of hospitalisation in children under 5 years of age?
RSV
97
How does RSV enter cells?
Via the fusion protein
98
What is the function of NS2?
NS2 causes the cytopathic effects
| NS2 is associated with the cytopathicity of the virus
99
What can NS2 cause?
It can cause morphological changes, loss of cilia and airway clogging
100
What was the main issue surrounding the formalin-inactivated vaccine?
This vaccine caused the symptoms of RSV to be worse
| It exacerbated the infection
101
Why did the formalin-inactivated vaccine exacerbate the RSV disease?
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
As a result of the vaccine how many children died?
Two toddlers died
103
Most children are infected with RSV at what age?
2-3 months
104
What are children mostly infected with between 6-12 months?
Human metapneumovirus
105
Human metapneumovirus genome and classification?
Mononegavirales order
-ssRNA
Group V
106
the second most common cause after human respiratory syncytial virus (RSV) of lower respiratory infection in young children IS?
Human metapneumovirus
107
Coronavirus family?
Cornaviridae
108
Coronavirus genome?
+ssRNA
109
Cornavirus baltimore classification?
IV
110
Human coronavirus causes?
Colds
111
What are two examples of zoonotic coronaviruses?
SARS
| MERS
112
SARS stands for?
Severe Acute Respiratory Syndrome
113
MERS stands for?
Middle Eastern Respiratory Syndrome
114
When was the SARS outbreak?
2003
115
Where did the SARS outbreak begin?
Southern China
116
When was the MERS outbreak?
2012
117
Where did the MERS outbreak begin?
Saudi Arabia
118
Animal reservoir of SARS?
Cave dwelling horseshoe bats
119
Animal reservoir of MERS?
Camels
120
When did SARS disappear?
2004
121
Why was SARS easier to control than a future influenza pandemic?
People are only infective once they begin displaying symptoms. Contrastingly, individuals infected with influenza can shed virus before they develop symptoms
122
MERS and SARS can both lead to the development of?
Pneumonia
123
What is the receptor for MERS?
DPP4 receptor
124
What is the DPP4 receptor?
Dipeptidyl peptidase 4
125
DPP4 stands for?
Dipeptidyl peptidase 4
126
Where is DPP4 present in humans?
In the lower respiratory tract
| On the alveolar epithelial cells
127
Where is DPP4 present in camels?
In the upper respiratory tract
128
Why is MERS not easily transmissible from human-to-human?
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
Adenovirus genome?
dsDNA
| Group I
130
What is an emerging adenovirus?
HAdV-55
131
Which countries has HAdV-55 infection been seen in?
Turkey, China, Korea, Spain
132
HAdV-55 was first observed in?
China
133
HAdV-55 is associated with which places?
Military camps
134
HAdV-55 is often?
Sporadic and random
135
What complications does it cause?
Severe pneumonia
