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INTRODUCTION TO
INFLUENZA
The (Ferret) Sneeze Heard Around The World: The
Case Of The Bioengineered Bird Flu
Case Study for AAC&U STIRS Project
Jill M. Manske
University of St. Thomas
Introduction to Influenza:
From: Bird Flu: A Virus of our own Hatching
http://birdflubook.com/a.php?id=56
THE INFLUENZA VIRUS:
-Has an RNA genome (8
genes)
-Highly variable virus
-Lipid envelope with
protein spikes
-Relatively unstable at
room temperature (half
life = a few hours)
-There is a species
barrier due mostly
structure of HA protein
What are the “H” and the “N” of
Influenza Viruses?
• HEMAGGLUTININ (HA) - The “H” in influenza names
• On the surface of the virus
• Functions as the receptor for the virus to bind to the host cell
• There are 17 different subtypes of HA (representing the numbers,
H1, H5, etc. in influenza naming)
• HA elicits an immune response and is part of the influenza vaccine
• NEURAMINIDASE (NA) - The “N” in influenza names
• On the surface of the virus
• Functions as an enzyme to let the new viral particles out of the host
cell
• There are 10 different NA subtypes
• NA is also part of the influenza vaccine
Important Note:
• The species which different types of influenza viruses are able to
infect are determined by HA receptor binding to different forms
of the receptor present on the host cell
• This provides a considerable species barrier between birds and
humans which is not easily overcome.
• Pigs provide a "mixing pot" - able to be infected by both types of
virus & thus allowing the passage of avian viruses to humans.
Types, Subtypes, Strains
• Types: Based on structure of internal proteins
• Type A: infects humans, birds, pigs, horses, other animals.
Wild birds are natural hosts
• Further Classified by Subtype (based on HA and NA
proteins) and strains based on antigenic drift (more later)
• Pandemics are associated with Type A
• Type B: Usually found in humans
• Classified by strain only
• Not associated with Pandemics
• Type C: Human infections rare
Classification(naming) of influenza strains:
•Type A, B or C/place isolated/number of isolate/year
isolated
•In the case of influenza A, also: HA subtype (H) and
NA subtype (N)
•For example, the three strains for the 2013/2014
vaccine are:
•A/California/7/2009 (H1N1)pdm09-like virus
•A/Texas/50/2012 (H3N2)
•B/Massachusetts/2/2012-like virus
•Quadravalent vaccine has additional
B/Brisbane/33/2008)
Examples of different subtypes and the
species they infect:
How the Flu Virus Changes: Antigenic shift
and drift
Flu viruses constantly
change and mutate.
Antigenic drift refers to
changes to the flu virus
that happen slowly over
time.
Antigenic shift results
when two different flu
strains combine and infect
the same cell and their
genomes combine. This
results in a sudden change
in the virus. This can result
in a pandemic strain.
More information can be found at:
CDC: How influenza viruses change
Example: Viral Reassortment of the 2009 H1N1
Pandemic Influenza Virus
A(H1N1)pdm09
Triple
reassortment:
7 genes from
avian and swine
1 gene from
human H3N2
http://www.virology.ws/2009/06/29/reassortment-of-the-influenza-virus-genome/
Spread Of The Virus
•Person to person via particle aerosols that can
get into respiratory tract.
- Can spread up to about 6 feet away
•Infectious about 1 day before symptoms and 5-7
days after symptoms.
- May be longer than 7 days in children
•The incubation period is short: - symptoms
appear 1 – 4 days after infection
•Viral titers (amounts) are usually high so there
are enough infectious virions in a small droplet to
start a new infection.
Seasonal Influenza:
• Seasonal influenza follows a predictable season
• Most people have some immunity due to previous
exposure to influenza viruses
• Seasonal influenza viruses change slightly
through antigenic shift
• Ahead of each influenza season we develop a
vaccine
• WHO estimates that worldwide seasonal
epidemics result in 3-5 million cases of severe
illness and 250,000-500,000 deaths every year
Pandemic Influenza
• Human influenza pandemics are a part of our
history
– 11 in the past 300 years
• Novel influenza virus subtype emerges in
humans with:
– little or no human immunity
– transmission of the virus to humans by
humans
– moderate to severe disease occurrence
What Happens After You Inhale Influenza Virus?
• After influenza viruses are inhaled, HA spikes on their
•
•
•
•
•
•
surfaces bind to molecules on the surface of cells lining
the respiratory tract.
Then the viruses are engulfed into the cell.
The viral components are released into the cell
The virus replicates its viral RNA and makes viral
proteins.
Newly formed viral particles migrate through the cell and
begin to bud through the cell membrane
The NA molecules on the surface of the new viruses allow
them to exit from the host cell
The newly formed viruses are released and find new cells
to invade.
What happened here?
An estimated 20-40 million people died during the1918-1919 Influenza Pandemic.
Learn more about the 1918 and other influenza pandemics
The “Bird Flu”: H5N1 Avian Influenza
The “Bird Flu”: H5N1 Avian Influenza
• Highly Pathogenic avian influenza (HPAI) H5N1 infection
•
•
•
•
is rare in humans
More than 600 cases have been reported since 2003.
Infection can lead to severe disease. Of the reported
cases, 60% of infected people died.
Most Cases of H5N1 in people have been linked to
contact with infected poultry
In the majority of cases, the person got HPAI H5N1 virus
infection after direct or close contact with sick or dead
infected poultry.
Source: CDC- Highly Pathogenic Avian Influenza in People. More
information
H1N1 vs H5N1 infection in humans
http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1#mediaviewer/File:H1N1_versus_H5N1_pathology.png.
622 cases: 371 deaths
Vaccines:
How to make flu vaccine?
Choose virus &
inject into fertilized
egg
2. Incubate egg and
allow for viral
replication
3. Collect allantoic
fluid from the egg full of live virus
4. Deactivate and
chop virus-- mix with
other strains for
seasonal vaccine
1.
http://www.niaid.nih.gov/SiteCollectionImages/topics/flu/Reassortment_HiRes.jpg
In the past few decades…
• 1973- WHO begins to recommend composition of
vaccine
• 1999- 2 sets of recommendations:
• Southern and Northern hemispheres
http://usatoday30.usatoday.com/news/health/2009-04-27-swine-flu-vaccine_N.htm
Today’s Vaccine Options
• 2013-14 Northern Hemisphere composition:
• Trivalent:
• A/California/7/2009 (H1N1)pdm09-like virus
• A(H3N2) virus (A/Texas/50/2012)
• B/Massachusetts/2/2012-like virus
• Quadrivalent
• Above three..
• B/Brisbane/60/2008-like virus
• Vaccines containing cell-cultured virus
http://news.harvard.edu/gazette/story/2009/
10/seasonal-flu-vaccine-update/