• Influenza viruses are divided into 3 groups determined by the ribonucleoprotein (RNP) antigen:

Important Proteins:

• Encoded by RNA segment #4
• Can agglutinate red blood cells - hence the nomenclature
• Cleavage by host-cell protease is required (resulting in HA1 and HA2) for infection to occur
• Influenza A strains occur according to minor or major changes in this gene. Influenza B strains change very slowly. Influenza C

• Encoded by RNA segment #6
• Enzyme that uses neuraminic (sialic) acid as a substrate
• Important in releasing mature virus from cells

Infection and Replication:

• Endocytosis follows receptor-specific virus binding to the target cell
  
• HA's conformation is altered by the low (acidic) pH inside the endocytotic vacuole causing the virus to uncoat
  
• The genome is transported to the nucleus
  
• Influenza's negative sense RNA is transcribed to positive sense to work as mRNA. This is achieved with the virus's RNA polymerase and the resulting RNA is double-stranded. From this "intermediate form" new negative sense can be synthesized for inclusion into new virions
  

Antigenic Shift:

• Reassortment of genes is a common feature of Influenza A, but not B or C
  
• When two different "A" viruses infect the same cell, their RNA segments can become mixed during replication
  
• New viruses produced in this way may survive due to a selective advantage within the population
  

Antigenic Drift:

• Constant mutations in the RNA of influenza which lead to polypeptide mutations
  
• Changes are less dramatic than those induced by Shift
  
• If these mutations affect HA or NA they may cause localised epidemics
  

• Transmission is by droplet inhalation and usually affects the upper respiratory tract
  
• Virus reproduces within the epithelium and destroys the cilia
• Epidemics and pandemics are due to the appearance of new strains so that an individual is continuously reinfected with unique strains
  
• Fewer virus particles are required to infect the lower respiratory tract than the upper
  
• One to three days after infection symptoms mediated by cytokines released from leukocytes and damaged tissues cause classic flu symptoms:
  Chills
  Malaise
  Fever
  Muscular aches
  Runny nose
  Cough
  
  
• Tissue damage may promote bronchitis and interstitial pneumonia;
  
• There is little to no associated viraemia (limited by IgG antibodies);
  
• Temperature usually decreases to normal by day three;
  
• Severity is generally proportional to the age of the sufferer;
  
• A twofold or greater rise in specific antibody titre in paired sera is diagnostic of recent infection and virus can be isolated from respiratory secretions during the initial stages of infection.
  
• Complications include:
  
  • Secondary bacterial pneumonia
    
  • Rarely indirect CNS disturbances (eg. encephalomyelitis)
    
• Vaccines based on inactivated virus or purified HA and NA proteins (from the most recent circulating strain) are available.
  
• Trials of rationally-designed drugs are in their final stages - these drugs bind to specific proteins interfering with the virus life-cycle.

• Antiviral drugs exist to treat (amantadine, rimantadine, zanamavir and oseltamivir) and prevent (amantadine, rimantadine, and oseltamivir) disease;
  
  
• Those benefitting most from the use of antivirals include those 65 years or older, children of 6-23 months of age, those with chronic medical conditions and pregnant women;
  
  
• Vaccines exist to prevent infection by influenza viruses.
  • A new vaccine strain can take months to grow, and some strains do not grow well using traditional methods;
  • When a new pandemic threat emerges, a high growth seed strain must be found quickly;
  • New methods may not need to grow "live" virus, but use reverse engineered viruses which grow well and express those parts of the virus which give us protection from infection;
  • Current vaccines provide 25 µg of the HA protein of 3 different influenza virus strains (2x FluA, 1x FluB) that are expected to be circulating for the next season;
  • In people who are already "primed", a smaller dose could be used to boost immunity;