1. 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

2. Introduction to Influenza: From: Bird Flu: A Virus of our own Hatching http://birdflubook.com/a.php?id=56

4. 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

5. 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

6. 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.

7. 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

8. 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)

9. Examples of different subtypes and the species they infect:

10. 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:

11. 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/

12. 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.

13. 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

14. 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

15. 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.

16. What happened here? An estimated 20-40 million people died during the1918-1919 Influenza Pandemic. Learn more about the 1918 and other influenza pandemics

17. The “Bird Flu”: H5N1 Avian Influenza

18. 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

19. http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1#mediaviewer/File:H1N1_versus_H5N1_pathology.png. H1N1 vs H5N1 infection in humans

20. 622 cases: 371 deaths

21. 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

22. 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

23. 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/