Emerging Diseases Lecture 12:

Influenza Virus and the 1918 Pandemic

12.1 Overview12.2 The pathogen-Influenza Virus A

12.3: Naming System12.4: A Disease of Birds

12.5: Antigenic Drift12.6: Antigenic Shift

12.7: Other Outbreaks12.8: 1918 “Spanish” Flu

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

12.2: The Influenza pathogen

• Virus called influenza virus• This is a picture of Influenza

A• Note the spikes or fibers on

the surface

Diagram of Influenza A particle

Hemagglutinin = HA or H: Neuraminidase = NA or NThere 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)

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 recognizes mainly the H protein.

12.3: Naming System1) 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 origin4) Code number of virus isolate5) Year of isolation6) H and N sub-type (e.g. H1N1)

Example:Influenza A/chicken/Hong Kong/220/97(H5N1)

12.4: Influenza A is a disease of birds

Wild birds transmit the disease to other wild animals, to domestic animals and to humans.

Transmission may be zoonotic

Zoonotic cycles

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

12.5: Antigenic Drift

Pressure from your immune system selects mutant HA and NA proteins

Accounts for most annual or seasonal flu outbreaksNot a change of subtype

Single mutations

Relativelyslow and gradual

Years

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

Antigenic ShiftDouble infection

with 2 virusesGene segments

are shuffled“Reassortant”

virus producedPopulation has

no immunity Rapid

Antigenic Shift and Pandemics

All the 20th century pandemics were caused by shift viruses

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

The 2009 Pandemic H1N1 Strain

• Many reassortment events• Birds, humans, pigs as hosts

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.

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

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

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

12.8: 1918 “Spanish” Flu

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?

Armed Forces Institute of Pathology

• Jeffery Taubenberger, Anne Reid

• Private Roscoe Vaughan• PCR

Determination of H gene

• Early in 1997• Private James Downs sample also positive

• Publication in Science March 21, 1997• More samples?

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

Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene Ann H. Reid*, Thomas G. Fanning, Johan V. Hultin, and Jeffery K. TaubenbergerThe “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 1918. 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 1918. 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 knownCloned and reconstructed in separate piecesBeing tested to determine why so deadlyMutation to provoke super immune response?