1. Emerging Diseases Lecture 12: Influenza Virus and the 1918 Pandemic
12.1 Overview
12.2 The pathogen-Influenza Virus A
12.3: Naming System
12.4: A Disease of Birds
12.5: Antigenic Drift
12.6: Antigenic Shift
12.7: Other Outbreaks
12.8: 1918 “Spanish” Flu

2. 12.1: Overview
“Influenza” = under the influence of evil spirits or bad air
Problematic for older, younger sufferers
Viral disease but can lead to secondary bacterial infections
1000s of deaths in US
each year

3. 12.2: The Influenza pathogen
Virus called influenza virus
This is a picture of Influenza A
Note the spikes or fibers on the surface

4. Diagram of Influenza A particle
Hemagglutinin = HA or H: Neuraminidase = NA or N
There are 18 H protein subtypes (H1-H18) and 11 N subtypes (N1-N11)
Most are found in various bird species.
Only restricted sets of subtypes occur in other species (H1, H2, H3 in humans-H5 and H7 very rarely)

5. They are responsible for attaching to cells.
H proteins and N proteins are important features on the surface of the virus.
They are responsible for attaching to cells.
When your body’s immune system attacks influenza, it recognized mainly the H protein.

6. 12.3: Naming System 1) What “type” of virus (influenza A, B or C)
2) What animal species did it come from? (omitted if from humans)
3) Geographic location of origin
4) Code number of virus isolate
5) Year of isolation
6) H and N sub-type (e.g. H1N1)
Example:
Influenza A/chicken/Hong Kong/220/97(H5N1)

7. 12.4: Influenza A is a disease of birds
Wild birds transmit the disease to other wild animals, to domestic animals and to humans.

8. Transmission may be zoonotic

9. Zoonotic cycles Pigs as “mixing bowl” for new types of flu virus?
Pigs have receptors for both human and bird viruses

10. 12.5: Antigenic Drift
Single mutations
Relatively
slow and
gradual
Years
Pressure from your immune system selects mutant HA and NA proteins Accounts for most annual or seasonal flu outbreaks Not a change of subtype

11. 12.6: Antigenic shift Another mechanism for change
Major change compared to drift
“Shifts” H or N subtype
H1 can shift to H2 or other
N1 can shift to N2 or other
Generally causes worldwide or pandemic strains

12. Antigenic Shift
Double infection with 2 viruses Gene segments are shuffled “Reassortant” virus produced Population has no immunity Rapid

13. Antigenic Shift and Pandemics
All the 20th century pandemics were caused by shift viruses

14. 2009 Pandemic
In 2009 a new shift strain emerged and began to spread in spring
Called “triple reassortant” because 3 shift reshufflings of genes involved
Birds, pigs, humans involved
By fall had spread worldwide, replaced out all other flu strains

15. The 2009 Pandemic H1N1 Strain Many reassortment events
Birds, humans, pigs as hosts

16. Antigenic Drift-Summary
Much slower than antigenic shift
Gradual accumulation of mutations
No change in subtype (i.e. H1 to H2)
Drift strains circulate from year to year, changing every year.
New vaccines are needed each year.

17. Antigenic Shift-Summary
Much faster than antigenic drift
Quick, major mutation
Change in subtype (i.e. H1 to H2) almost always
Shift strains start new pandemics
Old types of vaccines are useless

18. 12.7: Other Outbreaks “Hong Kong” 1997
H5 influenza common in birds-”bird flu” or “avian flu”
1985 Lancaster PA outbreak-highly pathogenic
1997 H5N1 “jumps” into
humans: 6/18 fatal

19. Additional Outbreaks H5N1 is usually highly pathogenic in humans
HPAI = highly pathogenic avian influenza
But not easy to transmit from human to human thank goodness
Tends to occur only when much bird-human contact

20. 12.8: 1918 “Spanish” Flu

21. The 1918 virus was a mystery In 1918 viruses were not well-known
It was thought that the 1918 pandemic was caused by a bacterium
Influenza A virus not purified until 1930’s (from pigs and ferrets)
Primitive technology relative to today
Samples from 1918?

22. Armed Forces Institute of Pathology
Jeffery Taubenberger, Anne Reid
Private Roscoe Vaughan
PCR

23. Determination of H gene
Early in 1997
Private James Downs sample also positive
Publication in Science March 21, 1997
More samples?

24. Johan Hultin Had also searched for 1918 flu
Brevig Mission (aka Teller Mission) Alaska-1951
72/80 deaths
Excavate mass grave in permafrost-
Return in August 1997

25. Complete genetic sequence known
Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene
Ann H. Reid*, Thomas G. Fanning, Johan V. Hultin, and Jeffery K. Taubenberger
The “Spanish” influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.
Complete genetic sequence known
Cloned and reconstructed in separate pieces
Being tested to determine why so deadly
Mutation to provoke super immune response?