INTRODUCTION TO INFLUENZAThe (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 Hatchinghttp://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

CDC: How influenza viruses change

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:

Example: Viral Reassortment of the 2009 H1N1 Pandemic Influenza Virus

A(H1N1)pdm09Triple 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

• 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

Pandemic Influenza

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

http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1#mediaviewer/File:H1N1_versus_H5N1_pathology.png.

H1N1 vs H5N1 infection in humans

622 cases: 371 deaths

Vaccines:How to make flu vaccine? 1. 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 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/