L18: Influenza

Question 1

What is a virus?

Answer 1

Piece of genetic material in a protective coat/capsule

Question 2

What does the genetic material in a virus do?

Answer 2

Small or large contains all the information necessary for the virus to replicate but requires host machinery

Question 3

What is influenza?

Answer 3

Acute viral infection of the respiratory tract (nose, mouth, throat, bronchial tubes and lungs)
Highly infectious
Carriers may have mild or no symptoms

Question 4

When do most cases of influenza occur?

Answer 4

8-10 week period over winter

Question 5

What is the structure of influenza virus?

Answer 5

Orthomyxovirus–> spherical, enveloped viruses containing a segmented, negative strand RNA genome

Question 6

What is the influenza genetic material like?

Answer 6

ssRNA containing 8 genes
Coding for 11 proteins
Including 3 RNA polymerases (high error rates)

Question 7

What are the antigens found on the surface of the influenza virus?

Answer 7

Haemagglutinin (H)- 18 types- binds to cells of the infected person
Neuraminidase (N)- 11 types- releases the virus from the host cell surface

Question 8

How many types of influenza virus are there?

Answer 8

3 types A, B, C
A is the most severe–> causes pandemics and epidemics with significant mortality
B can be vaccinated against–> causes severe disease
C mild disease no seasonality

Question 9

Compare and contrast type A, B and C influenza virus?

Answer 9

Type A–> most severe, 8 gene segments, 10 viral proteins, M2 unique
Found in humans, swine, equine, birds and marine mammals
Antigen shift and drift
May cause large pandemics with significant mortality in young persons

Type B–> 8 gene segments, 11 viral proteins, NB unique
Humans only
Antigenic drift only, two main lineages cocirculate
Severe disease–> older adults or persons at high risk

Type C–> 7 gene segments, 9 viral proteins, HEF unique
Humans and swine
Antigenic drift only, multiple variants
Mild disease without seasonality

Question 10

How does the influenza virus replicate?

Answer 10

Negative sense single strand RNA–> needs transcribing to positive sense strand to be useful
Positive sense single strand RNA–> translated into lots more positive sense single strand RNA
OR
Negative sense single strand RNA–> converted into mRNAs–> translated into viral proteins

Then viral proteins and ssRNA assembled into nucleocapsids (viral proteins form a ‘shell’ around the ssRNA)
Nucleocapsids then leaves host cell and spreads to other people

Question 11

How is influenza transmitted?

Answer 11

Transmitted from person to person via respiratory route (coughing, sneezing, inhaling)
Three potential modes
1- Small particle aerosols (<10 micrometres mass diameter)- remain suspended in air for many hours
2- Large particles or droplets will typically fall to the ground within 3m of the infected person- infects individuals in direct contact
3- Viral particles could land on surfaces, where influenza viruses remain infectious- infect others through indirect contact

Question 12

What are the barriers to influenza virus tranmission?

Answer 12

Barriers to entry via the respiratory route

1) Respiratory epithelial cells covered by a thick glycocalyx and tracheobronchial mucus that can trap virus particles
2) Ciliated respiratory epithelial cells continually sweep mucus up from the lower respiratory tract into the upper respiratory tract, where it is usually swallowed
3) in the lung immunologic defenses include secretory IgA, Natural killer (NK) cells and macrophages

Question 13

How does the virus enter the cells?

Answer 13

Gets passed respiratory barriers
Influenza virus has Hemagglutinin protein on the surface
Neu5Ac (NANA) residues- sialic acid on glycoprotein/glycolipid which acts as a receptor for influenza virus
Entry then occurs via receptor-mediated endocytosis
Virion released into the cytoplasm

Question 14

How does the virus leave cells?

Answer 14

Virus replicates inside the host cell
Pushes out into the plasma membrane of the host cell
Haemagglutinin and neuroaminidase coat the outside of the cell
Haemagglutinin remains attached to the glycoprotein on the outside of the host cell
Neuroaminidase cleaves the sialic acid releasing the cell
Virus infected cell can then go and infect other cells

Question 15

What are the symptoms and complications of influenza?

Answer 15

Fever, headache, confusion, dry cough, sore throat, nasal congestion, mylgia and fatigue
Complications–> meningitis/ encephalitis, pneumonia, sinusitis/bronchitis/pharyngitis

Question 16

What is the time course of influenza virus A infection?

Answer 16

Incubation period- 1-5 days
Clinical symptoms- 3-9 days
Most people recover within 2-7days

Question 17

Who is most at risk of complications from influenza virus?

Answer 17

• Children under 6 months
• Older people (age over 65)
• Those with underlying health conditions such as respiratory disease, cardiac disease, long-term neurological conditions or immunosupression
• Pregnant women–> perinatal mortality, prematurity, smaller neonatal size and lower birth rate
• Morbid obesity BMI> 40

Question 18

How is influenza diagnosed?

Answer 18

Usually diagnosed from symptoms and clinical presentation
Are lots of other methods available, each very with the amount of time required
Nasopharyngeal swab
Antigen detection
Immunofluroescence etc…

Question 19

What is the treatment for influenza?

Answer 19

1) Antivirals–> Inhibit viral uncoating after uptake probably through M protein–> not commonly used because of resistance–> Influenza A
2) Neuroaminidase inhibitor–> inhibits viral release from infected cells, causes aggregation of viral particles in both influenza A and B–> Tamiflu and Relenza
3) Prevention

Question 20

How is influenza prevented?

Answer 20

Vaccinations

• Formalin-inactivated vaccine (quadrivalent/trivalent) by injection of influenza A and B
• Live, attenuated (slightly changed to weaken it), cold-adapted vaccine (quadrivalent) by nasal spray for influenza A and B

Question 21

What is meant by trivalent or quadrivalent?

Answer 21

Trivalent- Vaccine 3 strain
2 influenza A strains and 1 influenza B strain

Quadrivalent- Vaccine 4 strain
2 influenza A strains and 2 influenza B strains

Question 22

How does the neuroaminidase inhibitor work?

Answer 22

Blocks the neuroaminidase activity
Prevents cleavage of sialic acid
Cell unable to move away remains tethered to host cell

Question 23

Why do genetic changes occur in the influenza virus?

Answer 23

Flu virus constantly replicating
Life cycle approx 6 hours
Viral RNA polymerase have high error rate and lack proof reading ability–> mutations
Genetic variation and resistance
Mutations often occur in surface antigens hemagglutinin and neuraminidase

Question 24

What is antigenic drift?

Answer 24

Minor changes in H and N antigens
Small point mutations
Accumulation of mutations over time
Does not involve changes in viral subtype

Question 25

What is the link between antigenic drift and vaccines?

Answer 25

Vaccines change every year to account for antigenic drift

WHO makes recommendations on the strains on influenza A and B that are predicted in the following winter

Question 26

What is antigenic shift?

Answer 26

Dramatic changes in the antigenic properties of the H and/or N proteins- occur suddenly
Occurs infrequently- maybe 10-20 years
Only influenza A
Change in subtype e.g. from H1N1 to H3N2
Surface antigens hemagglutinin and neuroaminidase from different species
Causes widespread epidemics and pandemics

Question 27

How does reassortment of antigens in antigenic shift occur?

Answer 27

1. Influenza A occurs in many animals (pig, equine, birds, humans etc…)
2. Re-assortment occurs between influenza A viruses in different species–> pigs can infected by human influenza and avian influenza
3. Possible in environments where animals and humans coexist
4. Re-assortment can occur in one host animal–> mRNAs in pig encoding H and N antigens re-assorted into unique combinations
5. Re-assorted virus can then spread among humans, birds and other pigs

Question 28

What is the major problem with antigenic shift?

Answer 28

Leads to new subtype of influenza
Not seen in population so no immune defence against it
Spreads easily due to transmission method and incubation period 1-5 days so you can be a carrier without symptoms

Question 29

Define epidemic?

Answer 29

Prevalent among a community at a special time

Produced by some special cause not generally present in the affected locality

Question 30

Define pandemic?

Answer 30

Epidemic over a very large area

Affecting a large proportion of a population- often the world

Question 31

How does flu actually kill people?

Answer 31

Body’s response to viral infection
Antibodies triggered and immune cells move to site of infection
Release of cytokines leading to local inflammation
Immune system can overreact–> produce T cells which attack and destroy the tissue in which the virus is replicating, in particular the lungs
Opportunistic secondary infection–> usually in the lungs, overwhelms the body’s immune system unable to cope