W28 - Viral pandemics and influenza

Question 1

the 2 viruses responsible for pndemics in the 21st century are:

Answer 1

the 2 viruses responsible for pndemics in the 21st century are = SARS-CoV-2, infleunza

Question 2

How many pandemic influenzas took place in the past?

Answer 2

4!

Question 3

How many people died as a result of the 1918 Spanish flu pandemic?

Answer 3

50 million

Question 4

The natural reservoir of influenza A virus is…

Answer 4

Ducks (aquatic birds)

Question 5

What are the 2 spike proteins in influenza virus?

Answer 5

1. Haemagglutinin (HA)
2. Neurominidase (NA)

Question 6

Why can’t avian influenza viruses infect humans too well?

Answer 6

Avian influenza viruses (in ducks) are not evolved to spread too well between humans and also cause too severe of a disease in humans because viruses are intracellular and so the adapt to their host usually. the identity of cellular machinary in birds will be diff to humans = this is called host gene barrier

Question 7

What is an imp mutation that avian influenza needs to hve to be able to replicate/spread in humans?

Answer 7

mutation in PB2 subunit => changes ANP32 protein

Question 8

What is antigenic shift?

Answer 8

Influenza virus have 8 gene RNA segments, which means if 2 strains co-infect and replicate in the same cell, you could get a mixing of genetic content = reassorted virus with new host range and replication cabalities = antigenic shift

google definition: antigenic shift, genetic alteration occurring in an infectious agent that causes a dramatic change in a protein called an antigen

Question 9

Antigenic shift will lead to adapted influenza virus that has the potential to cause pandemics - T or F?

Answer 9

False - Antigenic shift is not sufficient for evolution of a pandemic virus.

The virus will be able to infect human/mammalian cells, but it needs to become adapted to being spread from human-to-human

Question 10

Human influenza viruses transmit between people in…

Answer 10

airborne droplets

Question 11

What limits avian influenza to transmit between humans?

Answer 11

Avian flu HA can bind to human receptors in deep lungs (hence cause severe disease and death, for example amongst those working in poultry markets), however it cannot bind well to receptors in the URT, so can’t spread between humans.

It needs to acquire affinity for human receptors to be able to penetrate mucus and infect epithelial cells

Question 12

Describe pH & its relationship with avian influneza entry + airborne droplets

Answer 12

virus floats in through air, lands on receptor, endocytosed => the virus expeirences this mildly acidic environment of early and late endosome, this triggers virus to release its genome and start replicating. the HA component is pH sensitive

airborne droplets => the first droplet is mildly acidic, but as water evaporates, the concentration of ions, including H+, will increase = the pH goes LOW (ACIDIC). avian influenza viruses are very fragile in pH and they become inactivated in the air before they are picked up by next individual.

Question 13

Name 3 main adaptations avian influenza needs to have to be able to infect humans

Answer 13

1. Polymerase change
2. HA change (to bind better to URT)
3. Altered ability to survive low pH

Question 14

Several antiviral drugs already exist for influenza, and are licensed for use in the clinic. However unlike HAART for HIV we don’t use them together. T or F?

Answer 14

true - they are not licensed to be used in combination

Question 15

What is the MOA of neuraminidase (NA) inhibitors?

Answer 15

the virus uses NA to bud out of infected cells

• if patient is taking an NA inhibitor drug, that drug would be blocking the NA = the virus would be tethered to the cell surfce = halt viral replication and virion woul be picked up and killed.

Question 16

NAI drug name (1)

Answer 16

tamiflu

Question 17

MOA of new anti-influenza drug Baloxavir

Answer 17

targets and blocks polymerase by inhibiting polymerase acidic (PA) endonuclease

Question 18

The influenza vaccine given to those at greater risk of complications from flu in the UK is

A) A live attenuated virus

B) A purified fraction containing HA and NA of an inactivated virus

C) A purified HA protein expressed in insect cells

D) An immunoglobulin fraction from sera of immune patients.

Answer 18

B) A purified fraction containing HA and NA of an inactivated virus

Question 19

Who is the live attenuated flu vaccine given to?

Answer 19

The live attenuated, cold adapted virus limited to URT is given to children, and causes a humoral and cellular immune response

Question 20

Universal flu vaccine - what will it target?

Answer 20

bnAbs which target the stalk region which is preserved amongst strains

Question 21

What type of virus is a coronavirus?

Answer 21

RNA genome, single-stranded + sense RNA

enveloped virions

Question 22

SARS and SARS Cov 2 bind to cells via…

Answer 22

ACE2

Question 23

The most likely origin of SARS CoV2 is:

1. Wild waterfowl
2. Horseshoe bats
3. Created in a laboratory
4. Pangolins

Answer 23

Horseshoe bats most likely (Cov with 99% similarity has been found in bats)

Pangolins (Cov with 96% similarity)

Question 24

A COVID patient in ITU is most likely to benefit from

1. Kaletra, a combination of lopinavir and ritonavir usually used to treat HIV
2. Hydroxychloroquine, an antimalarial
3. Remdesivir a nucleoside analogue
4. Dexamethasone, a steroid.

Answer 24

4. Dexamethasone, a steroid.

Question 25

There is loss of vaccine effectiveness against symptomatic disease from omicron infection - T or F?

Answer 25

True

efficacy against delta was near 90-ish%

efficcy against omicron falls to 70-ish%