S10 Influenza

Question 1

What two general things do viruses consist of?

Answer 1

• a delivery system - protects the virus against degradation in thee environment and contains structure used to bind to target cells in the host
• payload - contains the genome and enzymes necessary to initiate the first steps of virus replication

Question 2

What is flu?

Answer 2

An acute viral infection of the respiratory tract (nose, mouth, throat, bronchial tubes and lungs).

It is highly contagious, even those with mild/no symptoms can infect others

More common in winter

Question 3

What type of virus is the influenza virus? What is it’s structure?

Answer 3

Orthomyxovirus

Spherical, enveloped virus containing a segmented*, negative stand RNA genome

• each segment codes for one polypeptide

Question 4

What are the 2 surface antigens on influenza virus?

Answer 4

• Haemagglutinin (H) - binds to cells of infected person

* Neuraminidase (N) - releases virus from host cell surface

Question 5

What are the types of influenza viruses?

Answer 5

Influenza A
Influenza B
Influenza C

Question 6

What are the natural hosts of Influenza A, B and C?

Answer 6

A - humans, swine, equine, birds, marine mammals

B - humans only

C - humans and swine

But don’t often see transmission from animal to human

Question 7

What is antigenic drift?

Answer 7

Minor changes (natural mutations) in the genes of flu viruses that occur gradually over time (so can cause seasonal epidemics)

Question 8

Which influenza is most severe, important?

Answer 8

Influenza A - most likely to cause a large pandemic with significant mortality for young people

Question 9

What are the main animal reservoir for influenza A?

Answer 9

Birds, particularly wildfowl

• birds migrate

Question 10

What are the clinical manifestations of influenza B?

Answer 10

Less severe disease with smaller outbreaks, usually effects older population

But the burden of disease is mostly in children

Question 11

How does the influenza virus replication?

Answer 11

1. Negative ssRNA
2. Transcribed into positive ssRNA
3. Translated into more negative ssRNA
4. Negative ssRNA assembled into nucleocapsid

Or

2. ssRNA leads to mRNA due to RNA polymerase in virus
3. Viral proteins produced
4. Viral proteins assemble into a nucleocapsid

Question 12

How is influenza virus transmitted?

Answer 12

From person to person via respiratory route - coughing, sneezing, inhaling

• small-particle aerosols - remain suspended in air for many hours
• larger particles or droplets - typically call to ground within 3m of infected person so infect individuals in direct contact
• viral particles could land on surfaces and remain infectious - indirect contact

Question 13

What are the barriers to entry via the respiratory route?

Answer 13

• respiratory epithelial cells covered in thick glycocalyx and tracheobrnchial mucus that can trap particles
• ciliates respiratory epithelial cells sweep mucus up from lower respiratory tract into upper respiratory tract, then swallowed
• in the lungs we have immunological defences including secretory IgA, NK cells and macrophages

Question 14

How does the influenza virus enter cells?

Answer 14

1. The virus have Hamagglutinin protein on surface
2. NANA residue (sialic acid on glycoprotein/lipid on host cell surface acts as a receptor for virus
3. Entry via receptor-mediated endocytosis

This occurs in upper respiratory tract

Question 15

How does the influenza virus leave the host cell?

Answer 15

1. H protein attached to sialic acid/receptor

2. Neuraminidase cleaves the bind between H protein and sialic acid

Question 16

What are the symptoms of influenza?

Answer 16

• fever, headache, confusion
• dry cough, sore throat, nasal congestion
• nausea, vomiting, diarrhoea (more common in kids)
• myalgia (muscle pain), fatigue

Question 17

What are the complications of influenza?

Answer 17

• MENINGITIS/ENCEPHALITIS, febrile convulsions
• pericarditis, myocarditis
• SINUSITIS/BRONCHITIS/PHARYNGITIS, PNEUMONIA
• increased maternal complications, increased risk of prematurity, lower birth weight, myositis, rhabdomyolysis

Question 18

What is the incubation period of influenza A virus?

Answer 18

1-5 days, average 2-3 days

Question 19

What are the sudden onset symptoms?

Answer 19

Fever
Chills
Headache
Muscle/joint pain
Extreme fatigue
Dry cough
Sore throat 
Stuffy nose

Question 20

How does someone normally overcome influenza A?

Answer 20

Usually self-limiting

Recovery time 2-7 days

Question 21

Who are the risk of complications of influenza most serious in?

Answer 21

• young children (under 6 months)
• older people (over 65 years)
• underlying health conditions - respiratory disease, cardiac disease, long-term neurological conditions, immunosuppression
• pregnant women
• morbid obesity (BMI of 40+)

Question 22

How do you diagnose influenza?

Answer 22

Tests e.g. antigen detection, viral RNA/nucleic acid detection

But usually diagnose based on symptoms and clinical assessment

Question 23

What are the treatments for influenza?

Answer 23

• antivirals - usually not used due to resistance - inhibits viral uncoating after uptake (A) e.g. rimantadine
• Neuraminidase inhibitors - inhibit viral release from infected cells and causes aggregation of viral particles (A and B) e.g. oseltamivir (Tamiflu)
• prevention - formalin-inactivated vaccine (injection), live vaccine (nasal spray) (A and B)

Question 24

What is the life cycle of influenza virus?

Answer 24

6 hours - lots of potential for errors e.g. viral RNA polymerases

Leads to mutations, genetic variation and resistance

Question 25

What does this mean the WHO have to do in terms of vaccines for influenza?

Answer 25

Monitor virus epidemiology worldwide to make recommendations on the strains predicted to be circulating in the future, so need to adapt vaccines to this

Question 26

Describe the changes in the influenza A virus.

Answer 26

Have dramatic changes in the antigenic properties of H and/or N proteins, occurs infrequently, there’s a change in subtype - surface antigens (H and N) from different species

Question 27

What is antigenic shift?

Answer 27

Major changes in the genes of flu viruses that occur suddenly when two or more different strains combine. Results in a new subtype and can cause widespread epidemics/pandemics

Question 28

How does the reassortment of influenza genes (antigenic shift) occur?

Answer 28

1. There are influenza A viruses in many animals e.g. horses, pigs, wild migrating waterfowl 2. Reassortment can occur between influenza A viruses that can infect different animal and avian species e.g. pigs can be infected by human- and avian-specific influenza viruses 3. In environment where pigs, birds and humans coexist, it’s possible for a pig to be simultaneously infected with multiple influenza subtypes 4. Reassortment can occur within one host animal e.g. pig, mRNAs encoding H and N antigens are reassorted into unique combinations 5. Reassorted virus has the potential to spread among humans, birds and pigs

Question 29

What are the consequences of antigenic shift?

Answer 29

Leads to a new subtype of influenza virus so immune systems of many may have no defence against the new subtype, can lead to: * epidemic - prevalent among people/community at a special time and produced by special causes, not generally present in the affected locality * pandemic - epidemic over large area, usually worldwide

Question 30

How does flu actually kill people?

Answer 30

The immune system overreacts - T cells attack and destroys tissues in which the virus in replicating e.g. the lungs Can get opportunistic secondary infection e.g. bacterial infections by Strep or Staph e.g. in the lungs

Question 31

How did the Spanish flu kill people?

Answer 31

Virus jumped species This triggered a violent response in the human host lead to a “cytokine storm”