Lecture 15- Resp Viruses

Question 1

Respiratory Syncytial Virus (RSV)

Answer 1

Cause of bronchiolitis
Peak incidence in winter months
More- slide 4

Symptoms;
-similar to common cold
- 2 to 3 days= symptoms peak + can become more severe; rapid shallow breathing, rasping/persistent cough, faster than normal heartbeat + chest wall retractions

Question 2

Respiratory Syncytial Virus (RSV)

Answer 2

Cause of bronchiolitis
Peak incidence in winter months
More- slide 4

Symptoms;
-similar to common cold
- 2 to 3 days= symptoms peak + can become more severe; rapid shallow breathing, rasping/persistent cough, faster than normal heartbeat + chest wall retractions

Question 3

Influenza

Answer 3

Acute infectious disease; mild to severe symptoms, fatal
Influenza virus; A, B or C
^outbreaks occur in winter - cold + dry, virus more stable at low temp + small droplets in winter due to low humidity
Vaccine for high-risk individuals

Question 4

Influenza A

Answer 4

Most virulent
Infects human + animals; ducks, chickens, pigs, etc
Cause of worldwide pandemics
Subtypes; H1N1, H5N1 Etc

Disease profile; slide 11 + 12

Question 5

Influenza B + C

Answer 5

Infects humans
Less common than influenza A
Mutation rate 2-3x lower than A
Type B= pandemics don’t occur
Type C= less common

Question 6

Uncomplicated ‘Normal’ flu

Answer 6

Fever 38-40 degrees
Headache
Photophobia, tears, ache
Dry cough, nasal discharge
GIT symptoms

Question 7

Pulmonary complications

Answer 7

Croup = young children; cough, difficulty breathing
Viral pneumonia
Secondary bacterial infection; streptococcus pneumoniae etc
Build up of fluids + lack of ciliary clearance provide a good environment for bacteria
Complications= COPD/ Heart disease patients

Question 8

Infection + Recovery

Answer 8

Virus infects the epithelial respiratory cells
-Cells die due to viral infection + impact of immune system; interferon + cytotoxic cells T cells
-Efficiency of ciliary clearance reduced
-Impaired function of mucus
-Reduced clearance of infections agents
-Gaps in the epithelium allow pathogen access

Recovery;
- interferon may play a role by decreasing virus production
- symptoms of flu due to efficient induction of interferon
- cell-mediated immune response is importation in viral clearance
- antibody response not significant until after virus has been cleared
- repair of epithelium begins quickly but may take time

Question 9

HA (hemagglutinin) protein

Answer 9

-Involved in attachment + membrane fusion
-Receptor binding site on the virus is in a pocket + not exposed to the immune system
-antigenic domains are on surface+ can be altered without changing the receptor
-allows immune avoidance

Question 10

NA (neuraminidase) protein

Answer 10

NA protein digests sialic acid
Present on cell surface
Promotes virus binding + endocytosis
Removal of sialic acids= easier for the virus to diffuse away once they leave the cell
Also involved in penetration of the mucus layer

Question 11

Influenza virus evolution

Answer 11

Antigenic shift;
-changes in H + N spikes
-probably due to genetic recombination between different strains infecting same cell

Antigenic drift;
-mutations in genes encoding H/N spikes
-may involve only 1 AA
-allows virus to avoid mucosal IgA antibodies

Question 12

Seasonal vs pandemic

Answer 12

Epidemic/seasonal;
-annual, minor changes in genes + drift NOT shift

Pandemic;
-shift NOT drift, human A strain acquire genes from animal strains

Question 13

Antivirals

Answer 13

2 neuraminidase (NA) inhibitors approved in UK
Oseltamivir (Tamiflu) + Zanamivir (Relenza)

Question 14

COVID-19

Answer 14

Mild-moderate illness in people (cold/flu)

4 genera; alpha, beta, gamma- + delta-
-beta= most clinically important genera, 5 subgenera- s29

Single-stranded positive-sense RNA viruses

Question 15

SARS- Severe Acute Respiratory Syndrome

Answer 15

Two outbreaks- 2002 + 2004
Highly contagious, life-threatening form of pneumonia crossed over from small animals
Cases; s30

Disease; Covid-19
Virus; SARS CoV2, approx 6m deaths worldwide

Start of pandemic -s35

Question 16

Receptor-binding domain (RBD)

Answer 16

RBD= in the spike protein bind to the ACE2 receptor
RBD= most variable part of the coronavirus genome
6 RBD AA= critical for binding to ACE2 receptors + the host range of SARS- CoV- like viruses

• improve receptor binding
• computational analyses suggests it is still not ideal
• strong evidence for natural selection + intermediate host

Question 17

Angiotensin converting enzyme- II (ACE2)

Answer 17

COVID- used the ACE2 enzyme on the cell surface as a receptor
Stops ACE2 doing the job it’s meant to do
Has a range of functions + is present on a range of cells not just the lungs
Negative regulator of the renin-angiotensin system (RAS) ; modulates systemic fluid-salt-balance and bp, expression promotes dilation of blood vessels
^why diabetic + hypertensive individuals are at a greater risk

Question 18

Cell entry and the immune response

Answer 18

Use of ACE2 entry point= avoids some antiviral interferon pathways- instead a range of proinflammatory mediators are stimulated; e.g. IL-6 + IL-8
^recruit neutrophils to the site + generated an inflammation response- pneumonia
*inhibits the development of regulatory T-cells = dampen immune response
*reduces effectiveness of cytotoxic t-cells that would kill the infected cells

Question 19

Disease progression

Answer 19

Slides 40-42

Question 20

Complications + long-term complications of Covid

Answer 20

43-45

Question 21

Cytokine storm

Answer 21

Rest of slides