Stertz

Question 1

How many major proteins encoded by IAV ?

Answer 1

11.

Question 2

Entry mode for IAV ?

Answer 2

Receptor mediated endocytosis.

Question 3

Reminder, who does the cap snatching?

Answer 3

PB2 binds the caps and PA cuts them.

Question 4

How is splicing done for IAV?

Answer 4

Basically to make the few accessory proteins they just use the cellular machinery. It’s not super efficient with viral transcripts tho, so you get both variants of the protein produced.

Question 5

Stronger binding HA to sialic acids require, as a consequence…

Answer 5

… A more active NA.

Question 6

What’s the evolutionary plasticity of HA compared to MeV glycoproteins ?

Answer 6

It’s reaaally super loose. It can handle a shit ton of mutagenesis without any problems, whereas Measles just hates it.

Question 7

What’s a subtype of IAV referred to?

Answer 7

Type of HA and NA, and there’s no cross reactivity of antibodies between subtypes.

Question 8

What’s the fun little thing about H7N9 receptor binding ?

Answer 8

It’s an avian strain that binds quite well to human sialic acids.. Pandemic much ?

Question 9

what’s the error rate of IAV RdRp ?

Answer 9

10 000 nucleotides 1 error.

Question 10

what are the two approaches to generate a potentially universal IAV vaccine ?

Answer 10

Chimeric HA approach or headless HA approach.

Question 11

Name a neuraminidase inhibitor and a PA inhibitor

Answer 11

Oseltamavir (NA)

Baloxavir (PA)

Question 12

Are HAV, HBV and HCV all part of the same happy family ?

Answer 12

No - A is a picorna, B a Hepadna and C a Flavivirus. Even their genomes are different, as HBV has a dsDNA genome.

Question 13

So HBV is a bit shit. Only 5% of infected people don’t clear the virus and get symptoms… However it has another, more grave effect, which is it ?

Answer 13

HBV infection increases the risk of Hepatocellular carcinoma at all stages of infection - might be due to its DNA integration or of persistant liver damage sustained during chronic infections.

Question 14

Give a structure overview of HBV virions.

Answer 14

Small (40 nm) enveloped virus, with three glycoproteins: LMS (Large Middle Small).
3kb genome. partially dsDNA.

Question 15

What is CCC DNA ?

Answer 15

Covalently Closed Circular DNA. it’s the template for transcription by the polII.

Question 16

HBV has a tiny genome (3kb). how does it optimise transcription ?

Answer 16

Firstly, it has a few alternative start codons (L/M/S).
ORF are overlapping (FS).
An unique Polyadendylation signal is used for all transcripts!

Question 17

What’s a bit special about HBV packaging, regarding the genome?

Answer 17

The RNA is packaged in the particle, and inside of it reverse transcription starts.

Question 18

What are the two treatments available to fight HBV infection, and what’s their main aim symptom-wise?

Answer 18

You can either use pegylated interferon, which has a low risk of getting countered by the virus but gives serious side effects, or using nucleoside/tide analogs, that have little side effects but induce resistance.

The goal is to limit the risk of developing carcinomas in chronic infections, as these treatments do no cure the infection.

Question 19

what’s the favored hypothesis regarding HCV carcinoma induction?

Answer 19

Probably more likely because of the sustained damage of the liver, as it’s an RNA virus that doesn’t integrate anywhere.

Question 20

How’s HCV maximising the potential of its 9.6kb genome?

Answer 20

Its (+) RNA genome makes a single polyprotein - cellular proteases can cut the first few proteins out, then the viral protease gets released and takes over for the rest.

Question 21

Once uncoated, what does HCV do ?

Answer 21

It creates those weird double-membraned vesicles wih all the enzymes embedded in.

Question 22

What were older treatments against HCV ?

Answer 22

Interferon + Ribavirin, and Protease inhibitors.

Question 23

What are current treatments against HCV ?

Answer 23

combination of protease, polymerase and NS5A inhibitors. super efficient with minimal side effects.
Unfortunately, it’s quite expensive and theres not vaccine, like for HBV.

Question 24

What’s the def of serotypes ?

Answer 24

Essentially it’s a strain that can be targeted by certain antibodies but not other from other strains.

Question 25

What are the two types of vaccination ?

Answer 25

Passive, where you transfer directly components of the immune response to the patient (Rabies, Ebola). Usually after exposure. Ex; monoclonal antibodies.
Active, where you induce the immune response in the patient.

Question 26

How can viruses be attenuated for vaccine use, and how does that translate into its biology?

Answer 26

Attenuation through serial passaging in nonhuman cells.

Can have either loss of fitness, different tropism, temperature sensitivity or loss of immune response modulators.

Question 27

Can an attenuated virus from a vaccine revert to its former self ?

Answer 27

in the case of the live polio vaccine, yes. Its neurovirulence is lost, but it can revert back to a transmissible, virulent virus.

Question 28

What’s the pros and cons of a live vaccine ?

Answer 28

Pros: they give a potent and long immune response through both T and B cells reponses.
Cons: May revert, and there’s a chance of transmit weird undiscovered viruses from the cultures the attenuated ones are made in.

Question 29

How are inactivated viruses made?

Answer 29

Wt virus inactivated with formalin: it’s fast and safe but not the most efficient.

Question 30

Examples of inactivated vaccines:

Answer 30

Rabies, Polio Salk, HepA.

Question 31

Besides live and inactivated virus vaccines, what other options are available ?

Answer 31

Fractionation (purified subunits)

Cloning-based: DNA vaccines, or virus vector based, or protein expression.

Question 32

What are the severe limitations of IAV vaccines ?

Answer 32

Limited efficiency, strain specificity, annual production, and lag phase for pandemics.

Question 33

Give an example of a viral vector-based vaccine and its advantages.

Answer 33

Advantages: good immune response with no virulence. Example: VSV + Ebola vaccine.

Question 34

What’s the things to take into account when making the mRNA vaccine ?

Answer 34

It must be a bit modified to be less immunogenic, and packaged into liposomes or nanoparticles.