Influenza

Question 1

1. Which influenza strain causes most human disease?

2. Which other strains also contribute?

Answer 1

1. A; about 70%

2. B &C: about 20-30%

Question 2

1. How is influenza spread?
2. Why is it more prevalent in winter?
3. How is influenza normally resisted?

Answer 2

1. sneezing; virus suspended in secretions
2. less humidity, so droplets are suspended in air longer; in warmer months, humidity is higher, so droplets become heavy and drop to ground
3. mucus layer (barrier to flu virus entrance), cilia beating “up and out”; alveolar macrophages

Question 3

Influenza Symptoms and Recovery

1. What are symptoms associated with?
2. What is important in viral clearance?
3. When does the antibody response develop?

Answer 3

1. efficient induction of interferon
2. interferon production and cell mediated immune response
3. not significant until after virus has been cleared

Question 4

Influenza Pathogensis

1. What cells does it infect?
2. What happens next?
3. What happens to airways?

Answer 4

1. lung epithelia
2. infected epithelia and macrophages produce proinflammatory cytokinesl exuberant immune responses cause lethargy, muscle aches, fever
3. necrotic infected cell debris and inflammatory infiltrates occupy the airway –> impeded breathing

Question 5

Influenza Pathogenesis: 1. What happens to infected cells? why?

2. What does 1 cause?
3. What is rare in influenza?

Answer 5

1. death due to either virus or interferon
2. reduced efficacy of ciliary escaltor, reduced clearance of infectious agents from respiratory tract, gaps in protective epithelium –> access to cells for other pathogens which can lead to bacterial pneumonia
3. viremia

Question 6

What are possible complications for the following age ranges?

1. infants
2. Age 65
3. What other groups may be at risk for longer infection periods?
4. What should be considered for these pts?

Answer 6

1. smaller airway passages
2. less developed or waning immunity
3. pregnant, morbidly obese, asthma, COPD, immunosuppresion
4. antiviral therapy

Question 7

Virion

1. Gross morphology
2. genome
3. Function of NP protein
4. Function of M1 protein

Answer 7

1. pleiomorphic: can be filamentous or oblong
2. 8 segments of negative strand RNA
3. coats RNA
4. Matrix protein that helps give virion rigidity

Question 8

5. Function of M2 protein
6. Function of HA protein
7. Function of NA protein

Answer 8

5. ion channel
6. binds to sialic acid on cells
7. neuraminidase that cleaves sialic acid on cells that have already been infected

Question 9

Hemagglutinin Protein

1. Structure
2. What binds sialic acid?
3. Where do Ab bind?

Answer 9

1. 3 stems (HA2) and 3 large globules (HA1)
2. each large globule can bind sialic acid
3. several epitopes on bulbous part

Question 10

How do virions release genome?

Answer 10

Influenza virus particles enter cells by receptor-mediated endocytosis;
endosome has H+ which enter through the M2 pore;
This causes the vRNA to become free;
then the membranes fuse and vRNA is released into the cytoplasm

Question 11

1. Where does the viral RNA go in the cell?
2. What does it do there?
3. Why isn’t there viremia?

Answer 11

1. the nucleus
2. it has a polymerase that cleaves host mRNA to create primers to create template RNA that makes the viral proteins
3. virus enters and exits on the apical side of the cell due to presence of viral proteins on the apical side; this restricts virus to airways

Question 12

1. What are the largest outbreaks called?
2. Smallest?
3. Ones in the middle?
4. Antibody patterns re: pandemics

Answer 12

1. pandemic
2. endemic
3. epidemic
4. Antibodies to a certain strain continue to rise after a given pandemic; the next pandemic usually has a different Ag, so the antibodies to the first pandemic drop, and those to the second pandemic rise

Question 13

1. What happens when influenze replicates?
2. why?
3. What does this mean practically?
4. What is this called?
5. What structure does this occur in?

Answer 13

1. errors are translated
2. RNA-dependent RNA replication is error prone
3. structures can be altered making them antigenically distinct
4. drift
5. hemagglutinin spikes; can create epidemic virus

Question 14

1. Apart from error-prone replication, what can cause influenza pandemics?
2. What time scale do influenza A antigenic types reappear on?

Answer 14

1. RNA segment reassortment –> dramatically altered antigenicites
2. roughly equivalent to 1 human generation

Question 15

1. When are influenza virus vaccines effective?
2. What are they classified/characterized by? (5)
3. What is the virus grown in?
4. How is vaccine administered?
5. What is the ideal target/role for antibodies?

Answer 15

1. if they represent the currently circulating virus strain
2. Serotype (A, B, or C); host of origin, geography location of isolate, strain number and year of isolation, HA and NA subtypes
3. Chicken eggs
4. IM
5. block influenza HA protein activity, which prevents virus entry/membrane fusioin

Question 16

What are the two main types of anti-influenza drugs?

Answer 16

Block M2 proteins; block neuraminidase

Question 17

Mechanism of M2 blocking drugs

Answer 17

Blocks M2 pores so H+ doesn’t enter the virion; RNA is not released from virion proteins so the infection is blocked at the entry stage; genome is basically inert

Question 18

Mechanism of neuraminidase blocking drugs

Answer 18

prevent cleavage of sialic acid on already infected cells; this means that newly released virions tend to re-infect cells that have already been infected; this slows virus dissemination, shortening disease and recovery time