Lecture 6: Influenza Flashcards
What is the structure of the influenza virus
It is made of chunks of viral RNA enclosed in the membrane that it stole from a cell. On the outside they have proteins sticking out from the surface of the membrane called Antigens- (hemagglutinin and neuraminidase)
Why can a flu strain be a pandemic strain
This is a new strain depending on the H,N combination of the virus subtype
Why can a flu strain be a pandemic strain
This is a new strain depending on the H,N combination of the virus subtype
How does pandemic strain influenza A kill (spanish flu) and who did it affect the most
Causes an overreaction of the body’s immune system causing lots of cytokines. Inflammation of the lungs great so people drown in fluid. Affects younger people with good immune response.
What are the 7 main steps of the virus life cycle
- Virus adheres to the healthy cell membrane
- Virus gets endocytosed
- Virus membrane fuses with vesicle membrane to release RNA outside nucleus
- Viral RNA hijacks the genetic machinery of the cell to duplicate RNA.
- Viral proteins are made- antigens + RNA
- Viral proteins assemble near the cell membrane where it buds cell membrane into a new virus
- New virus adheres again but is cleaved off to be released.
What are the 7 main steps of the virus life cycle
- Virus adheres to the healthy cell membrane
- Virus gets endocytosed
- Virus membrane fuses with vesicle membrane to release RNA outside nucleus
- Viral RNA hijacks the genetic machinery of the cell to duplicate RNA.
- Viral proteins are made- antigens + RNA
- Viral proteins assemble near the cell membrane where it buds cell membrane into a new virus
- New virus adheres again but is cleaved off to be released.
What is the role of Hemagglutinin
It binds to sialic acid receptor on healthy cell membrane of the lungs, promoting the endocytosis of the virus (molecular recognition)
What is the role of Neuriminidase
In a new virus, it is an enzyme that will recognise the sialic acid carbohydrate part of the sialic acid receptor binding to hemagglutinin and cleave sialic acid away from the rest of the chain so the virus that can leave
What is the structure of the sialic acid receptor
Membrane protein with galactose at the bottom connected to a sialic acid at the top through a glycosidic bond.
What causes the host range restriction
The glycosidic bond between sialic acid receptors in humans is 2-3 whereas in birds its 2-6 and this affects whether…
What causes the host range restriction of birds vs humans
The glycosidic bond between sialic acid and galactose in receptors in humans is 2-6 (bent) DIFFERENT to in birds its 2-3 (linear) and this affects whether a Hemoglutinin can recognise it and bind.
What is the difference between the types of flu of humans and birds, and why can’t humans catch bird flu directly from birds
Birds can catch any type H1-16, N1-9 whereas Humans can only catch H1,N1 H2N2 H3N2 so cannot get some of the bird flus. Humans only have bird flu receptors in the lungs while the upper nasal tract has only human receptors so only easy to get it from bird slaughter.
What caused bird Flus
to affect humans and make pandemic viruses
(the role of domesticated animals in the spread of influenza pandemic strains)
Pigs have both types of receptor (bird and human) within the respiratory tract. It is also at the right temperature for bird flus. So it can catch bird virus and the human virus. This can cause a mixing of the viral RNA in the host cell to produce a combination Virus which is the pandemic strain.
Describe the process how neuraminidase inhibitors were designed using protein structures to guide the design process.
- See how the natural substrate binds in the binding pocket of neuriminidase (sialic acid)
- Look for opportunities in the pocket to make inhibitor with stronger affinity
- Make sure it is strong enough that you don’t need don’t
How does Relenza and Tamiflu treat influenza
These are inhibitors of the neuriminidase with 10,000 stronger binding than sialic acid due to the replacement of OH with arginile (positively charged). These stop viruses from spreading further and infecting more cells.
