Session 10: Influenza

Question 1

Flu is an acute viral infection of what?

Answer 1

Respiratory tract (nose, mouth, throat, bronchial tubes and lungs)

Question 2

Give some features of influenza virus.

Answer 2

Highly infectious illness which spreads rapidly in closed communities. Resp. tract infection Even people with mild or no symptoms can infect others Mostly during winter

Question 3

Structure of influenza virus (orthomyxoviruses)

Answer 3

Spherical, enveloped containing a segment negative ssRNA genome. Include 3 RNA polymerases with high error rates.

Question 4

Influenza have two surface antigens. Which?

Answer 4

Haemagglutinin (H) 18 types Neuraminidase (N) 11 types

Question 5

What does H antigen do?

Answer 5

Binds to cells of the host of the infected person.

Question 6

What does N antigen do?

Answer 6

Releases the virus from the host cell surface

Question 7

Why is it important to not that the 3 RNA polymerases of influenza virus have high error rates?

Answer 7

It means that mutations are likely to occur.

Question 8

What types of influenza viruses are there? (3 main groups)

Answer 8

Influenza A Influenza B Influenza C

Question 9

Natural host range of Influenza A.

Answer 9

Humans, swine, equine, birds, marine, mammals. However animal -> human transmission is not likely.

Question 10

Natural host range of Influenza B.

Answer 10

Humans only

Question 11

Natural host range of Influenza C.

Answer 11

Humans and swine

Question 12

Epidemiology of Influenza A.

Answer 12

Antigenic shift and drift

Question 13

Epidemiology of Influenza B.

Answer 13

Antigen drift only

Question 14

Epidemiology of Influenza C.

Answer 14

Antigenic drift only

Question 15

Clinical manifestations of Influenza A.

Answer 15

May cause large pandemics with significant mortality in young persons.

Question 16

Clinical manifestations of influenza B.

Answer 16

Severe disease generally confined to older adults or persons at high risk.

Question 17

Clinical manifestations of Influenza C.

Answer 17

Mild disease without seasonality.

Question 18

Features of influenza A.

Answer 18

Cause outbreaks most years and are the usual cause of epidemics and pandemics. Live and multiply in different animals and may spread between them.

Question 19

Features of influenza B.

Answer 19

Tend to cause less severe disease and smaller outbreaks and predominantly found in humans. Specifically in children.

Question 20

Explain replication of the influenza virus.

Answer 20

It all stems from a negative ssRNA which is read and processed by RNA-dependent RNA polymerase (RdRp). The negative ssRNA can therefore turn into two strands of mRNAs or a positive ssRNA they are effectively the same thing and have two different fates. +ssRNA can turn into 4 strands of -ssRNA to become the new -ssRNA in a new virus. The mRNAs code for viral proteins which will assemble the nucleocapsids. This all happens in the cytoplasm.

Question 21

Three potential modes of transmission of influenza virus.

Answer 21

Influenza virus is transmitted from person to person via resp- route and therefore coughing, sneezing and inhaling.

1) small-particle aerosols which can remain in air for many hours non-direct contact.
2) larger particles or droplets will typically fall to the ground within 3 m of the infected person and infect individuals in direct contact.
3) Viral particles could land on surfaces where the influenza virus can remain and be infectious for hours and infect others through non-direct contact.

Question 22

Barriers to prevent entry of the influenza virus via the respiratory route.

Answer 22

Resp. epithelial cells covered by a thick glycocalyx and tracheobronchial mucus that can trap the virus particles.

Mucociliary escalators

In the lungs immunologic defenses include secretory IgA, NK cells and macrophages

Question 23

How does the influenza virus enter cells?

Answer 23

H antigen binds to host.

NANA residues act as receptors for influenza virus and forms an endocytotic vesicle.

This means that the virus enters via receptor-mediated endocytosis.

Question 24

How does the influenza virus leave the cells?

Answer 24

Neuraminidase (N antigen) cleaves the binding that H antigen has with the host cells glycoprotein.

So during exocytosis the newly formed vesicle is still in contact with the membrane of the host cell. But the N antigen cleaves and stops this interaction.

Question 25

Symptoms of influenza.

Answer 25

Fever Headache Confusion Dry cough Sore throat Nasal congestion Nausea, vomiting and diarrhoea Myalgia and fatigue However up to 75% have no symptoms!

Question 26

Complications of influenza (most important ones)

Answer 26

Meningitis/encephalitis Otitis media Croup Sinusitis, bronchitis and pharyngitis Pneumonia

Question 27

Incubation period of influenza A virus infection.

Answer 27

1-5 days with an average of 2-3 days. Sudden onset of symptoms.

Question 28

Which people are at highest risk of serious complications of influenza?

Answer 28

Children under six months Older people over 65 People with underlying health conditions + immunosuppressed Pregnant women Morbidly obese

Question 29

Diagnostic testing of influenza?

Answer 29

Usually sample from nasopharyngeal swab. Rapid influenza diagnostic tests testing for antigens. Rapid molecular assay Immunofluorescence RT-PCR Rapid cell culture Viral tissue cell culture

Question 30

Treatments for influenza.

Answer 30

Antivirals (rimantadine, amantadine) which inhibit viral uncoating after uptake. Neuraminidase inhibitors like tamiflu and relenza. Which inhibit the viral relase from the infected cell. Prevention like formalin-inactivated vaccine for influenza A and B Live, attenuated, cold-adapted vaccine by nasal spray in influenza A and B

Question 31

Explain the genetic changes in the influenza virus. Why is mutation common? What is mutated? What kind of epidemiology does this suggest?

Answer 31

The viral RNA polymerases have high error rates and there is also lack of proofreading which means a lot of mutations will occur. The surface antigens (H and N) will be mutated. This is antigenic drift

Question 32

# Define antigenic drift. What is the consequence of antigenic drift?

Answer 32

Minor changes (natural mutations) in the genes of viruses that occur gradually over time. This causes seasonal epidemics.

Question 33

Explain antigenic drift when it comes to influenza virus.

Answer 33

Minor antigenic changes in H and N proteins that occur each year. **_The antigenic drift does not involve a change in the viral subtype._** They are simply random mutations in viral RNA and single or a small number of amino acid substitutions in H and N proteins.

Question 34

Explain antigenic shift in influenza A virus.

Answer 34

These are dramatic changes in the antigenic properties of the H and/or N proteins (antigens) This occurs very infrequently and maybe every 10 or 20 years. It is only the influenza A virus which shows antigen shift. **_There is a change in subtype of the antigen._** An example is H1N1 goes to H3N2. This means that there are surface antigens (H and N) from different species.

Question 35

Define antigenic shift.

Answer 35

Major changes in the genes of flue viruses that occur **_suddenly**_ when to or more different strains combine. This results in a _**new subtype_**. Causes widespread epidemics/pandemics.

Question 36

Why does antigenic shift happen?

Answer 36

Reassortment of different RNA segments from each species in a new capsid. There is potentially no previous immunity to the new subtype.

Question 37

How does the reassortment occur in influenza A that causes antigenic shift?

Answer 37

In environments where pigs, birds and humans co-exist. This means that a pig might get infected by two different subtypes of influenza A. This means that reassortment can occur between the two subtypes and create unique combinations.

Question 38

Consequences of antigenic shift.

Answer 38

Leads to a new subtype of influenza virus. Immune systems may not have any defence against the new subtype. Can lead to epidemics and pandemics.

Question 39

How does flu actually kill people?

Answer 39

Body's immune response to viral invasion where antibodies are triggered and immune cells move to site of infection with the release of cytokines leading to local inflammation. So one of two may happen: A) Immune system overreacts and CTLs start to attack and destroy the tissues in which the virus is replicating in lungs particularly. B) There is an opportunistic secondary infection like Streptococcus or Stapylococcus species usually in the lungs.