2. Virion Structure and Organization
RNA envelope virus
Endemic in waterfowl; epidemic in humans
Genome composed of eight RNA segments (7 in influenza C)
Proteins hemaggluttinin (HA) and neurominidase (NA); 17 H and 10 N
Influenza C structurally different, compositionally similar
Copycat virus: Rhinovirus ; RSV

3. History The “Spanish Flu” of 1918
Killed as many as 25 million in the first 25 weeks, whereas HIV/AIDS killed 25 million in the first 25 years
Killed ~5% of human population

4. Visualization of blotted membrane by X-ray film and data analysis
Infection and Replication
Infection and Replication
1)Influenza virus attaches to the surfaces of epithelial cells (mainly in respiratory areas)
2) HA is important for the attachment of the virus to the sialic acid receptors of human cells, and NA is important for the release. M2 channels are important for viral changes
3)Soluble host cell proteases cleave the HA into two parts, HA1 and HA2. This activates the virus (this is a key step)
4) The virus is internalized by early endosomes by clathrin mediated endocytosis
5) In late endosomes, the pH drops triggering the conformation of the cleaved HA molecules. HA1 opens up and allows HA2 to form a triple alpha helix bundle which extends to the endosomal membrane. This causes the fusion of the viral and endosomal membrane
6) The viral genome is then released into the cytosol
7) The 8 segments make their way into the cell nucleus, and the production of the new virus begins. The virus is polyadenylated and capped and exported and translated like host mRNA.
8) Just hours after the initial infection, thousands of viral daughter cells bud off through M1 matrix complex,
9) NA has receptor-destroying activity, cleaving sialic acid. The daughter cells go off and infect neighboring cells.
10) We have generated antibodies capable of fighting off the virus. They specifically bind to HA and are internalized with the virus. When the pH drops in late endosomes, the antibodies remain bound to a highly conserved epitope of HA. The antibodies now block the conformational change HA preventing viral fusion. The trapped virus degrades
11) Some cells also prevent the initial cleavage of HA preventing host proteases from activating the virus
Visualization of blotted membrane by X-ray film and data analysis

5. Three Types/Naming the Virus
Symptoms
Epidemic
Vaccine
Genetic Drift
Genetic Shift
Pandemic
Animals
A (most common)
Resp/Constit.
yes
Birds. Pigs. Horses. dogs B no C
Resp
Pigs, dogs
H- something, N-Something
Standard Nomenclature
Type (family), species isolated from (if non-human), location, isolate #, isolate yr, HA/NA subtype
A/Panama/2007/1999 (H3N2)

6. Evolution of Influenza
Antigenic Shift
Antigenic drift

7. Symptoms and Diagnosis
Abrupt
3-7 days
Respiratory
Stuffy nose
Sore throat
cough
Constitutional
Fever/chills
Body aches
fatigue
CDC definition (Influenza-like illness ILI): sore throat or cough AND fever
Quick way to distinguish cold from flu
Cold viruses don’t have constitutional symptoms

8. Treatment Testing for Flu Antiviral Drugs for Influenza
Don’t usually test unless 
need for further testing
to figure out what kind of medication to prescribe
need to know the type for infection control
Rapid Test
Antiviral Drugs for Influenza
Amantadine and Rimantadine  block M2
Oseltamivir (pill) and Zanamiver (powder) block Neuraminidase (NA)– Age Restriction
Why treat patient?
High risk
<2 yo , > 65 yo
Pregnant
Chronic Disease (weak immune system)
Severe Disease/ hospitalization

9. Prevention Wash hands Don’t touch your face Avoid sick people Vaccine
 University of Michigan
Placebo vs. dead virus
VE (Vaccine Efficacy)  60%-70%
2014 VE= 61% According to the CDC
 TIV and LAIV Vaccines
Making Flu Vaccine Steps
Strain (WHO)  Manufacturing Eggs (millions) safety (FDA) Distribution Clinics YOU!

10. Flu Surveillance
Hospitalized per year (global): 3,000,000-5,000,000 ; (US) 200,000
Die per year (global): 250, ,000 ; (US) 3,000-49,000
Weekly US MAP (CDC)
Flu Doctor  HospitalCounty  StateUS (Atlanta)

11. Current Research Upper Respiratory area – Human virus receptor
Lower Respiratory area- Avian virus receptor
Current Research
How to prevent new pandemics of influenza viruses—H5N1 outbreak
Some H5N1 viruses are adhesive to human upper respiratory tissue
Study showed that bronchiolar area may be site of viral receptor specificity change
To prevent pandemic, must stop avian human transmission and get rid of prolonged infection of patient

12. References
Ahmed R, Oldstone MB, Palese P. Protective immuniity and susceptibility to infectious diseases: lessons from the 1918 influenza pandemic. Nature Immunol 2007; (March 17):
Bouvier NM, Palese P. The Biology of influenza viruses. Vaccine 2008 (March 17): D49- D53
Centers for Disease Control and Prevention. (2014) Seasonal Influenza (Flu). Retrieved from
Shinya,K. et al. Avian flu: influenza virus receptors in the human airway. Nature 440, (2006).
Stegmann T. Membrane fusion mechanisms: the influenza hemagglutinin paradigm and its implications for intracellulare fusion. Traffic 2000; 1 (March 20):
Uyeki T: Human Infection with Highly Pathogenic Avian Influenza (H5N1) Virus: Reviews of Clinical Issues. (2009) Clinical Infectious Diseases : Retrieved from
World Health Organization. (2014) Health topics: Influenza. Retrieved from