Influenza and Cold - Influenza, Rhinovirus, Adenovirus (Franco Falcone)

Question 1

What are common colds?

Answer 1

Affect upper respiratory tract causing general symptoms such as: coughing, sore throat, runny nose, nasal congestion, sneezing, fever, muscle aches and fatigue.

Question 2

Which viruses commonly cause colds?

Answer 2

Rhinovirus (main cause)
Influenza
Adenoviruses
Human coronaviruses (but also by human parainfluenza, human respiratory syncytical virus, enteroviruses other than rhinovirus, metapneumovirus.

Question 3

How are flu / colds transmitted?

Answer 3

Airborne droplets (aerosols)
Direct contact with infected nasal secretions
Fomites: contaminated objects, (e.g. tissues)
Hand to hand contact
Hand-to-surface-to hand contact (e.g. door handles)

Question 4

What is the profile of influenza virus?

Answer 4

Large, enveloped, ss(-)RNA virus

A, B or C

Question 5

What is the profile of rhinovirus virus?

Answer 5

Small, enveloped, ss(+)RNA virus (picornavirus)

Question 6

What is the profile of adenovirus virus?

Answer 6

Large, non-enveloped dsDNA virus

Question 7

What do Coronaviruses cause?

Answer 7

Often in the press; causative agent of severe acute respiratory syndrome (SARs) and the newly identified Middle East respiratory syndrome

Question 8

What is Influenza A?

Answer 8

Infects humans, horses, pigs, other (also marine) mammals and birds

Question 9

What is Influenza B?

Answer 9

Infects humans and seals

Question 10

What is Influenza C?

Answer 10

Infects humas, pigs and dogs

Question 11

Do strains A, B, C Influenza cause epidemics?

Answer 11

No, they just cause mild respiratory symptoms

Question 12

What is the difference between endemic and epidemic?

Answer 12

Endemic: a disease that exists permanently in a particular region or population. Malaria is a constant worry in parts of Africa. Epidemic: An outbreak of disease that attacks many peoples at about the same time and may spread through one or several communities.

Question 13

What are the features of influenza virus?

Answer 13

Enveloped, ss(-)RNA, 80-120nm (large)
Characteristic spikes; proteins on surface of the virus that have a key role in the invasion of cells.
Hemagglutinin (HA) and Neuraminidase (NA)

Question 14

What is the structure of Influenza like?

Answer 14

Spherical lipid bilayer around the outside, protruding surface proteins (N, neuraminidase and H, hemagglutinin)
M2 ion channel from lipid bilayer to matrix
M1 matrix proteins supporting the lipid bilayer
Genome = 8 organised, separate (-)ssRNA molecules with transcription complexes and nucleocapsid.

Question 15

How are Influenza A subtypes categorised?

Answer 15

Based on the HA and NA proteins on their surface
There are 16 different HA proteins (H1-16)
There are 9 distinct NA subtypes (N1-9)

Which are all serologically distinguishable (i.e. antibodies to one virus subtype do not react to another subtype of antigen.) –> Vaccination problem

Question 16

How are Influenza subtypes recorded?

Answer 16

H1N1 (swine flu)
H5N1 (bird flu) etc
H1-16 N1-9

Question 17

What is the consequence of the variation in antigen on Influenza A viruses?

Answer 17

Immunity acquired for one strain by infection or vaccination confers little or no cross-protective immunity against other sub-types.

Question 18

How does the Influenza HA protein mediate attachment?

Answer 18

Attaches to sialic acid on the epithelial cell surface, followed by uptake in endosomes.

Question 19

What is the structure of sialic acid?

Answer 19

A transmembrane glycoprotein carrying a terminal sialic acid that acts as attachment sites for influenza viruses.
Sialic acid is attached to a galactose molecule in an alpha 2,3 glycosidic bond (the bond is cleaved by neuraminidase).

Question 20

How do enveloped viruses enter cells?

Answer 20

Fusion

Question 21

How can zoonotic influenza strains infect humans?

Answer 21

Genetic exchange between Influenza viruses from different hosts can create new subtypes.
For example, a pig may be infected with H1N1, H3N2 and H7N7
This genetic mixing pot can give rise to a new strain that can infect humans

Question 22

How does genetic exchange in viruses take place?

Answer 22

If a human is infected by two strains of a virus, they can enter the cell and nucleus independently. They are then copied and copies of both viral RNA’s can become micxed up. The mixture is then reassembled and packaged into a capsid that is released from the host cell. Multiple different genetic exchange products / new strains can be made and released from the cell.

Question 23

Once a virus has been taken up into the hosts lipid bilayer, how does it escape and enter cytoplasm?

Answer 23

The endosome contains proton pumps which gradually decrease the pH from 7 to 5. The M2 ion channel is also a proton pump which channels the protons into the virion, further lowering pH.
The lower pH results in fusion of the viral envelope with the endosome membrane and release of the viral genome into cytoplasm.

Question 24

How does Amantadine stop Influenza?

Answer 24

Blocks the M2 ion channel and interferes with the life cycle

Question 25

What is the role of Neuraminidase?

Answer 25

Enables viral release from host cell by cleaving sialic acid on host cell and from mucin to allow access to new target cells.

Question 26

How do Sialic-acid Mimic drugs work?

Answer 26

Mimic the natural ligand for NA, sialic acid.

Acts as a neuraminidase inhibitor.

Question 27

What are the main receptors for human rhinovirus (HRV)?

Answer 27

Intercellular Adhesion Molecule -1 (ICAM-1) and Low Density Lipoprotein Receptor (LDLR)
They are expressed on epithelial cells
HRV up-regulates ICAM-1 surface expression in infected cells. (positive feedback).

Question 28

What are adenovirus receptors?

Answer 28

Adenovirus recognises CAR, CD46 and several integrins recognising RGD loop.

Question 29

What kind of drugs are Tamiflu and Relenza?

Answer 29

Sialic Acid Mimic Drugs (Neuraminidase Inhibitors)