Lecture 4 Antivirals against influenza virus Flashcards
Name the 3 components that classify the influenza virus
RNA
-ve stranded
segmented
Orthomyxoviridae
How many flavors of influenza are there?
4 - influenzavirus A-D
Which is the most common influenza in humans?
Influenzavirus A
What flavor does the Australian flu come under?
Influenzavirus B
What is the lipid bilayer of the virus made from?
plasma membrane of the previously infected cell
Which variant M glycoproteins does influenzas A-C encode for?
Influenza A = AM2 protein
Influenza B = BM2 protein
Influenza C = CM2 protein
What is the difference between low pathogenicity seasonal flu and high pathogenicity influenza strains?
low pathogenicity seasonal flu - mild and common type of flu
high pathogenicity influenza strains - rare and severe, can cause deaths
name 2 examples of high pathogenicity influenza strains
Avian influenza (H5N1)
Spanish influenza (H1N1)
How is influenza virus transmitted?
Droplet inhalation - a sneeze, cough, breathing = small droplets enter the resp tract
Direct contact - sneezing, coughing and breathing = droplets on surfaces called fomites, contact between surfaces and mucosal cells, mediated by contaminated hands/fingers
What are the symptoms of the influenza virus?
Upper resp tract cells affected
Symptoms have rapid onset (24h after contact), peak at day 3, persist for 8/9 days
Tiredness
Sore throat
Runny nose
Headache
Fever Cough
Muscle aches
What are the 3 membrane proteins on the influenza virus?
M2 protein - specific to flavor of Influenza
Neuraminidase (NA)
Haemagglutinin (HA)
What shape is the influenza virus?
Rod-shaped
What is the matrix protein?
The sheet beneath the membrane
Describe the influenza virus life cycle
Virus binds sialic acid receptor via HA, becomes internalised → Low pH membrane fusion via HA → segments released into cytoplasm → segments imported into nucleus → RNA synthesis → RNA/RNP export → virus assembly at plasma membrane → release of viron
Explain step 1 virus attachment of influenza virus
HA recognizes sialic acid on the surface of ciliated epithelial cells HA binds to sialic acid via galactose protein
Explain step 2/3 virus entry of influenza virus
The virus is inside the endosome.
Escapes when virus envelope (matrix layer) fuses with endosome membrane - mediated by HA protein changing confirmation due to low pH 8.
RNA protein segments still cannot get out - release is mediated by M2 proteins forms a pore = influx of H+ ions
Matrix protein layer breaks down and segments are released.
Explain step 8 virus release of influenza virus
The virus now needs to infect new cells and needs to make sure that HA on released viruses does not bind to the receptor on the old cell as this would mean the virus does not spread.
Therefore, NA cleaves sialic acid from the previously infected cell (essential role).
Why is a new vaccine needed for influenza every year
The influenza virus rapidly mutates
Every year there is a different strain of the virus
Why is a stockpile of antiviral medication for influenza needed despite there being vaccines?
A vaccine is slow to make - 9 months
If a pandemic occurred then it would not be quick enough to make a vaccine
Antiviral would work against many strains
Name the 2 ways that influenza virus mutation occurs
Antigenic drift
Antigenic shift
What is antigenic drift?
- When enzyme genes are copied, mistakes are made
- Incorporation of single nucleotide changes into genome
- Leads to new virus formation
What is an antigenic shift?
Occurs when 2 different viruses infect the same cell
Allows genome segments to mix when virus assembly occurs = different proteins encoded
What are the 2 current targets for influenza antivirals?
M2 protein.
Neuraminidase cleaving protein.
What are the 2 names of drugs in the adamantanes class?
Amantadine
Rimantadine
