Viral pandemics Influenza and Coronaviruses

Question 1

What are three requirements for a virus to become a pandemic?

Answer 1

A pandemic virus will have novel antigenicity.

A pandemic virus will replicate efficiently in human cells.

A pandemic virus will transmit efficiently between people.

Question 2

What is the natural reservoir of influenza A viruses?

A. Pigs

B. Chickens

C. Ducks

D. Tigers

Answer 2

C. Ducks

Question 3

Which protein in human cells can support influenza replication?

Answer 3

ANP32 proteins are essential host cofactors that support influenza polymerase activity.

Question 4

How can influenza polymerase utilise shorter mammalian ANP32?

Answer 4

Influenza polymerase can adapt to utilize shorter mammalian ANP32 homologues by mutation in PB2 subunit.

Polymerase adaptation to mammals can be achieved by a single amino acid change in PB2 E627K.

Question 5

What needs to change in order for virus to successfully infiltrate humans?

Answer 5

Incoming virus needs to penetrate mucus and infect epithelial cells.

Question 6

What contributes to incompatibility of avian-origin influenza virus with human respiratory tract?

Answer 6

Low acidic pH of URT followed by neutral pH of LRT

Question 7

Why is influenza A currently incompatible with human-human transmission?

Answer 7

Avian influenza HA must adapt for transmission in humans by acquiring affinity for human receptors.

Influenza entry is pH dependent and HA protein is pH sensitive.

Question 8

Are antiviral medications for influenza used together or separately?

Answer 8

Antiviral medications for influenza are NOT licensed to be used together (like HAART).

Question 9

What are examples of neuraminidase inhibitors?

Answer 9

Oseltamivir

Zanamivir

Question 10

What do new influenza antivirals target?

Answer 10

Polymerase acidic protein endonucleases.

Question 11

What is an example of a polymerase acidic protein endonuclease inhibitor?

Answer 11

Baloxavir

Question 12

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 12

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

Question 13

What are the two types of influenza vaccine given in the UK?

Answer 13

Inactivated vaccine

Live attenuated vaccine

Question 14

What are features of the inactivated influenza vaccine?

Answer 14

Split or subunit- HA rich

Given to those at risk

Short term strain specific immunity mediated by antibody to HA head

Question 15

What are features of the live attenuated influenza vaccine?

Answer 15

Cold adapted virus limited to URT

Given to children

Broader more cross reactive immunity including cellular response

Question 16

What is the major influenza viral antigen?

Answer 16

Haemagglutinin

Question 17

What is the structure of a influenza spike protein (HA)?

Answer 17

Question 18

Where do most broadly neutralising Abs (bnAb) target?

Answer 18

HA stalk/stem

Question 19

To which parts of HA do current influenza vaccines generate a response?

Answer 19

Current vaccines generate specific Ab responses raised against immunodominant HA1 epitopes at five antigenic sites (Sa, Sb, Ca1, Ca2, Cb).

Question 20

What are coronaviruses?

Answer 20

RNA genomes, single stranded positive sense RNA, very large genomes.

Enveloped virions. 100nm

Nidovirales - A nested set of mRNAs from one large genome

Question 21

Which coronaviruses have caused disease in humans?

Answer 21

OC43, 229E, NL-63 and HKU-1 cause 20-30% common colds

SARS and MERS are zoonotic

Question 22

What do SARS and SARS-CoV2 bind to?

Answer 22

Angiotensin Converting Enzyme 2

Question 23

What causes the severe effects of coronavirus?

Answer 23

Virus dissemination

Immunopathology

Question 24

A COVID patient in ITU is most likely to benefit from:

A. Kaletra, a combination of lopinavir and ritonavir usually used to treat HIV.

B. Hydroxychloroquine, an antimalarial.

C. Remdesivir a nucleoside analogue.

D. Dexamethasone, a steroid.

Answer 24

D. Dexamethasone, a steroid.

Question 25

Why is dexamethasone used in COVID patients on ventilation?

Answer 25

Cheap and extensively used steroid.

RECOVERY trial found Dex was effective in those receiving oxygen or ventilated.

Reduced deaths in illest cohort by 1/3.

Now standard of care in UK.

Question 26

Which monoclonal antibodies have been trialed against COVID?

Answer 26

Regeneron

Sotrovimab

Question 27

Which small molecule antivirals have been trialed against COVID?

Answer 27

Molnupiravir: Targets polymerase, nucleoside analogue.

Paxlovid: Targets protease.

Question 28

Why is the COVID vaccine not effective against the Omicron variant?

Answer 28

Omicron has a large number of Spike mutations that affect antibody neutralization.