• Influenza viruses (IFVs) belong to the family Orthomyxoviridae
• Influenza A virus (IFAV) belongs to the genus Influenzavirus A
• Influenza B virus (IFBV) belongs to the genus Influenzavirus B
• Influenza C virus (IFCV) belongs to the genus Influenzavirus C
• Enveloped with pleomorphic structure ranging in diameter from 20 - 120nm
• Single stranded, negative sense, segmented, RNA (ssNSRNA) genome
• Influenza (the illness in humans) has many faces including seasonal (A: H3N2, H1N1; B), Avian (A: H7N7, H5N1..), swine and Pandemic (A: H1N1, H2N2, H3N2..?).

• The viral proteins are encoded by a multipartitie (many bits) RNA genome.
  
  
  
  
  
  
• Influenza viruses are divided into 3 groups determined by the ribonucleoprotein (RNP) antigen.
  A - This group is the cause of epidemics and pandemics and has an avian intermediate host (IH).
  B - This group causes epidemics and has no IH
  C - This group does not cause epidemics and causes mild disease
  
• Virus strains are eventually named according to influenza virus type, town where first isolated, number of isolates, year of isolation and major type of important proteins e.g. Influenza B/Hong Kong/330/2001.

PROTEINS

Haemagglutinin (HA)
• 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

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

• 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
  

• 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
  

• 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 (cases of a disease increase beyond what is normal or expected in an area or population) and pandemics (a very widespread epidemic but not necessarily resulting in more severe illness) are due to the appearance of new IFV strains against which we have insufficent immunity.
  
• In the 20th century there were three IFV pandemics in 1918-1919, 1957-1958 and 1968-1969.
• 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. Oseltamavir is a neuramindase inhibitor
  
  
• 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;

1. Fedson,DS, Pandemic Influenza and the Global Vaccine Supply. CID 2003;36:1552-1561