CH 105 - Chemistry and Society

1918 Pandemic and Avian Flu

01/26/2008

The following are Moodle readings (under influenza) that discuss the 1918 virus and the recent avian influenza virus

• Capturing the Killer Virus
• Structure of the 1918 Human H1
• Resurrection of the 1918 Virus - Science - Oct 05
• Resurrection of the 1918 Virus - Nature - Oct 05
• Hypothesis: Emerge of 1918 Flu in War Camps in France
• Clues to the virulence of Avian Flu
• Alarm over bird flu mutations
• Avian Flu: Crying Wolf?
• As SE Asian farms boom, stage set for pandemic

What Happened in 1918?

Background

1918 "Spanish" flu Distinguishing features:

• influenza epidemics kill about 50,000 in the US each year (about the same number of American troops that died in the Vietnam war).  The 1918 flu pandemic killed about 650,000 Americans and about 20-40 million worldwide. 
• Mortality rate high (2.5%) compared to 0.1% for modern epidemics
• most deaths in U shape curve as function of age (very young and very old die);  1918 flu had W shape with high death rate among 15-34 year olds.
• Isolated communities like Alaskan Eskimos mortality rates above 70% (most in 15-34 year olds).

Statistics

Credit:  Influenza 1918 - The American Experience

Credit:  Influenza 1918 - The American Experience

• Outbreak map and death statistics, US
• The American Experience: Influenza 1918
• By comparison, war deaths in the 20th century

What Made the Virus So Deadly

Possible Reasons

• unsanitary living condition in camps with victims
• many killed by bacterial pneumonia secondary to the primary influenza infection
• virus contained variant viral proteins (such as HA and NA) that made human cells more susceptible to viral infection (HA) and to viral dispersal (NA).  Such changes in the virus may have occurred through antigenic shift, antigenic drift (see below).
• a new influenza virus jumped directly from an animal (fowl) to human
• perhaps older people had encountered a less virulent form of the same virus before and had developed some immunity to it, accounting for high percentage of death in younger people.
• the virus interacted in some different way with the immune system to make it's effects more lethal.

Characteristics of Epidemic/Pandemic Viruses

Proteins from 1918 Influenza Virus (Type A)  

1918 HA has:

• 1918 HA salic acid binding site almost identical to avian HA

• some avian H5 and H7 have additional mutation at cleavage sit of HA0 -->  HA1 and HA2.  Ordinarily cleaved by specific protease found in gut..  With mutation, more basic amino acids added, allow cleavage by other proteases, and addition organ diseases. HA1 from 1918 doesn't have the extra basic amino acids. 

1918 NA:

• Few strains that infect mice have changes in NA that allow multiple-organ infectivity.  Not seen in 1918 NA. 

Using a process called reverse genetics, individual 1918 genes can be added to present strains to make hybrid virus.  These can be used in test animals such as mice or human cells in culture.

• Add NS1 1918 gene to present influenza  Normal NS1 prevent production of a host protein called interferon (IFN) which part of host defense.  1918 NS1 more effective at blocking IFN production of the infected cell.

• Hybrids with both 1918 HA and NA:  These were lethal in mice and resulted in multiple organ problems, and a large inflammatory response in lung.

• 1918 HA alone: intensive immune response. 

Structure Files:

• 1918 Human H1 (1rd8.pdb)
• Human H3 (2hmg)
• Avian H5 (1jsm)
• Swine H9 (1jsd)

Reference:

Stevens, J. et al. Structure of the Uncleaved Human H1 Hemagglutinin from the Extinct 1918 Influenza Virus.  Science, 303, pg 1866 (2004)

Gamblin, S. The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin. Science, 303, pg 1838 (2004)

Genetic Changes in the Virus - What Caused the Pandemic

Antigenic Drift

Antigenic Shift