Influenza

Question 1

Symptoms of influenza

Answer 1

Cough, fever, chills, muscle aches, headache, normal chest X-ray

Question 2

Duration of acute infection

Answer 2

Seven days or longer. Weakness and cough might persist for several weeks

Question 3

Incubation period

Answer 3

1 - 5 days

Question 4

Infectious period

Answer 4

5-6 days

Question 5

At-risk groups

Answer 5

Young, elderly, people with underlying chronic heart, lung, renal, metabolic condition

Question 6

Receptor bound by flu

Answer 6

Sialic acid-containing receptor on non-ciliated respiratory epithelium.

Question 7

Configuration of sialic acid

Answer 7

Bound by alpha-2-6 linkage to galactose

Question 8

Place in airways where flu particularly replicates

Answer 8

Large airways

Question 9

Factor contributing to fever

Answer 9

IL1

Question 10

Factor contributing to muscle aches

Answer 10

Interferon alpha

Question 11

Where later infection can occur

Answer 11

Ciliated epithelium of trachea and bronchi

Question 12

Bacterial pneumonia pathogenesis

Answer 12

1) Late-stage flu replicates in ciliated epithelium, deciliates it
2) Bacterial species colonise airways
- H. influenzae, staph. aureus, strep. pneumoniae

Question 13

How closely related are influenza types A, B and C?

Answer 13

Not closely related.

Question 14

Role of M1 protein

Answer 14

Capsid stability (matrix)

Question 15

Role of M2 protein

Answer 15

Ion channel.

Allows H+ into virus, causing matrix conformation change, RNPs can exit capsid

Question 16

Location of RNA-dependent RNA polymerase

Answer 16

Attached to ribonucleoprotein

Question 17

Number of ribonucleoproteins

Answer 17

Eight

Question 18

Genes encoded

Answer 18

Ten

Question 19

Total number of HA and NA subtypes

Answer 19

17HA, 10NA

Question 20

Type of genome

Answer 20

ssRNA, segmented into eight ribonucleoproteins

Question 21

Number of RNA polymerase subunits

Answer 21

Three

Question 22

Number of silalic acid receptors on HA

Answer 22

Three

Question 23

Number of sialic acid receptors on NA

Answer 23

Four

Question 24

Area of influenza replication

Answer 24

Nucleus of host cell (despite being RNA virus)

Question 25

Reason for replication in the nucleus

Answer 25

Spliceosome needed to separate gene products of RNPs with two genes

Question 26

Tryptase Clara origin

Answer 26

Clara cells, limited to respiratory tract

Question 27

Tryptase Clara role

Answer 27

Removes lysine from HA cleavage site. | Allows HA to change conformation at pH 5 in endosome, escape endosome

Question 28

Mannose-binding lectin

Answer 28

Looks just like C1a. | Can take role of C1a in complement cascade

Question 29

Role of innate immune system in influenza infection

Answer 29

Slow virus until adaptive immune system is ready

Question 30

Role of CD8+ in influenza immunity 1) 2)

Answer 30

1) Not long-lived 2) Recognise peptides from internal antigens of virus. These peptides are broadly cross-reactive between type A subtypes (NOT between A and B)

Question 31

``` Role of antibodies in influenza immunity 1) 2) 3) 4) ```

Answer 31

1) LIfelong response 2) Bind HA, NA, prevent attachment/release 3) Ab+C' lysis of infected cells 4) Preexisting antibodies neutralise input virus

Question 32

Antigenic drift

Answer 32

Formation of new strains within a subtype because of accumulated missense mutations

Question 33

Reason for greater number of mutations in RNA genomes

Answer 33

RNA genomes no more error-prone than others. | RNA-dependent RNA polymerase lacks proofreading system

Question 34

Effect of antigenic drift affecting HA/NA antibody-binding site

Answer 34

Antibodies can no longer bind/lower affinity binding. These mutations are selected FOR by natural selection

Question 35

Number of antibody-binding sites on HA

Answer 35

Five

Question 36

Duration of reverse-transcriptase PCR diagnosis

Answer 36

Hours - 1 day

Question 37

Duration of culture diagnosis (determine subtype)

Answer 37

Days

Question 38

Reverse-transcriptase PCR diagnosis: 1) 2)

Answer 38

1) RT-PCR sample | 2) Antibody strip captures nucleoprotein in lysed virus sample

Question 39

Culture diagnosis: 1) 2) 3)

Answer 39

1) 10-days eggs with embryo infected with virus 2) Allantoic fluid is sampled 3) Allantoic fluid haemagglutination tested

Question 40

Definition of seroconversion

Answer 40

Four-fold titre increase in antibodies

Question 41

Haemagglutination test

Answer 41

1) Influenza virus can bind sialic acid on red blood cells, causing them to agglutinate 2) Chicken RBCs have sample added. If virus is not present, cells sink.

Question 42

Reason for use of chicken RBCs in haemagglutination tests

Answer 42

RBCs are nucleated, so sink if there is no agglutination (as they are heavy)

Question 43

Haemagglutination-inhibition test

Answer 43

1) Antibody added to haemagglutination test. 2) If antibody can bind to flu, no haemagglutionation. Used to determine specific subtype of flu

Question 44

Influenza vaccine: 1) 2) 3)

Answer 44

1) Inactivated trivalent vaccine 2) H1N1, H3N2, influenza B strains 3) Intramuscular injection

Question 45

Influenza vaccine manufacture: 1) 2) 3)

Answer 45

1) Viruses grown in chicken eggs 2) Viruses purified from allantoic fluid 3) Virus chemically inactivated, detergent-disrupted

Question 46

Influenza vaccine effect on the immune system: 1) 2) 3)

Answer 46

1) Induces AB, not CD8+ response 2) 70% seroconversion in the healthy 3) After strains are selected, takes ~6 months to make vaccine

Question 47

Types of antiviral drugs for influenza: 1) 2)

Answer 47

1) Ion channel blockers | 2) NA inhibitors

Question 48

Ion channel blocker action: 1) 2)

Answer 48

1) Inhibit M2 channel function in the endosome | 2) H+ from pH drop cant enter virus, prevents endosomal escape

Question 49

Limitations of ion channel blockers

Answer 49

Only effective for type A influenza

Question 50

NA inhibitor action

Answer 50

1) Mimic sialic acid Zanamivir - (+)'ve guanidine binds bottom of NA pocket. Ostelamivir - Hydrophobic group fits into hydrophobic pocket in NA pocket.

Question 51

NA inhibitor limitations

Answer 51

Only effective if given within 2 days of symptoms

Question 52

NA inhibitor advantages

Answer 52

Effective for influenza types A and B