Starter Questions:

1. What did you think of this paper? Did you find it interesting? Is it important?

2. What tissues does influenza infect? What immune mechanisms are important at this site of infection?

3. This group hypothesized that increased innate immune responses might harm thehost and help the pathogen (influenza).Did this hypothesis surprise you? Why or why not?

Background

• 1918 influenza extremely pathogenic, killing ~50 million people world wide.

• H1N1 subtype…but other H1N1 subtypes are not so deadly…

• Previously shown that infection with virus containing the 1918 H1 and N1 resulted in massive macrophage and neutrophil infiltration…the cause of increased pathogenicity?

What do you guys think of this hypothesis?

• Hemagglutinin: receptor required for viral entry, binds to sialic acid reisdues on host cells.

• Neuraminidase: aids in viral release from host cells by cleaving sialic residues from surface of host cells.

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Influenza infectious cycle

Influenza strains used

Why did they decide to use the Tx/91 and 1918HA/NA:Tx/91 viruses for this paper?

rescued Tx/91

HA/NA:Tx/91

Tx/91

Fig. 1

Lung titers

Fig. 2

TX/91

1918 HA/NA:TX/91

Fig. 3

Fig. 4

ctrl antibody

Neutrophil antibody

Neutrophil antibody+clodronate liposomes

clodronate liposomes

PBS liposomes

Lung titers

Brain titers

Fig. 5

1918 influenza increases certain innate immune inflammatory responses and decreases type-I Interferon responses in infected monkeys.