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Introduction to Influenza

This case study explores the characteristics and transmission of the influenza virus, with a focus on the bioengineered bird flu strain. It discusses the role of the H and N proteins, the species barrier between birds and humans, and the concepts of antigenic shift and drift. The study also highlights the spread of the virus, seasonal influenza, and the occurrence of pandemic strains.

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Introduction to Influenza

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  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

  3. 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

  4. 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

  5. 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. Important Note:

  6. 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

  7. 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)

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

  9. 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

  10. 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/

  11. 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.

  12. 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

  13. 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

  14. 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.

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

  16. The “Bird Flu”: H5N1 Avian Influenza

  17. 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

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

  19. 622 cases: 371 deaths

  20. Vaccines:How to make flu vaccine? • Choose virus & inject into fertilized egg • Incubate egg and allow for viral replication • Collect allantoic fluid from the egg - full of live virus • Deactivate and chop virus-- mix with other strains for seasonal vaccine http://www.niaid.nih.gov/SiteCollectionImages/topics/flu/Reassortment_HiRes.jpg

  21. 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

  22. 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/

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