Emerging infectious diseases

Question 1

List 3 animal reservoirs that have played an important role in recent emerging viruses and provide one viral example for each.

Answer 1

• Birds: west nile virus? (bird plague)
• Bats: SARS-Cov-1
• Rodents: viruses in Arenaviridae e.g. Lassa fever etc

Question 2

List the 9 factors effecting disease emergence.

Answer 2

1. Microbial: virulence, evolution & adaptation
2. Social/behabioural: STD, HIV
3. Demographics: overcrowding, urbanistation
4. International travel & trade
5. Changing ecosyst.: deforestation, global warming
6. Economic development & land use: farming
7. Modern medicine: organ transplant, antibiotically resistant strains
8. Breakdown of public health measure: war, famine, poverty, inequality
9. Intent to harm: bioterrorism

Question 3

What are the primary and intermediate hosts that led to the emergence of the SARS-CoV-1?

Answer 3

Primary: Bats
Intermediate: Civets

Question 4

What mutation, in which viral protein lead to SARS-CoV-1 emergence?

Answer 4

Deletion in receptor binding domain of S protein (spike) = 2x AA ∆es

Question 5

What is the major difference between Bat SL-CoV and Human SARS-CoV-1?

Answer 5

Bat has no affinity to ACE2 receptor in humans (civets, bats), unlike the human SARS

Question 6

What is the main reason for SARS-CoV-2 spreading greater than SARS-CoV-1?

Answer 6

1: only spread when symptomatic
2: Can spread even if asymptomatic or pre-symptomatic

Question 7

Describe the replication cycle for SARS-CoV-2. 7 steps)

Answer 7

1. Receptor binding domain on S1 binds to ACE2
2. Conformational ∆ in spike = body of virus brought closer to cell
3. Transmembrane serine protease 2 (TMPRSS2) cleaves S1 from S2
4. Entry
5. Transcription => mRNA
6. translation => packaging & assembly
7. budding out

Question 8

Why is it thought that the Pangolin is the intermediate host for SARS-CoV-2?

Answer 8

bc the receptor binding domain of human & pangolin CoV are similar to each other

Question 9

What were the effects of the D614G mutation for the SARS-CoV-2.

Answer 9

Aspartate (D) –> Glycine (G)
=> change conformation in receptor binding domain = Higher AFFINITY to ACE2 receptor

Question 10

Name the mutations in the RBD for the UK, South African and Brazilian variants. Which mutations seems to be most important and why?

Answer 10

UK: N501Y
Brazil.: N501Y, E484K
S.Africa: N501Y, E484K, K417N
*N501Y: Inc binding affinity to ACE2 (direct interaction)= more infectious = spread more

Question 11

Why is the omicron variant of SARS-CoV-2 thought to be less pathogenic (although it spreads more rapidly)?

Answer 11

• same affinity to ACE2 as original SARS-Cov2 & less than delta
• infects cells in URT = less pathogenic