Influenza pandemics have been recognized for centuries, but the virus responsible was not isolated until 1933. Influenza virus particles are highly variable in shape. Mostly are spherical or oval and 80-120 nanometres (nm) in diameter, but long filamentous particles also occur (up to 2000 nm long). Different strains of virus vary in their tendency to form filaments – this property depends on the matrix protein of the virus, which lines the inner side of the virus envelope. The outer surface of the particle consists of a lipid envelope with glycoprotein spikes of two types:
Haemagglutinin (HA) and Neuraminidase (NA)
Influenza virus particles are quite fragile (they have a half-life of a few hours at room temperature), and are sensitive to drying out, sunlight and warmth. The core of the virus contains eight genome segments which consist of RNA as the genetic material plus a virus protein called the nucleoprotein or N protein.
- Influenza A viruses such as H5N1 infect a wide variety of mammals, including humans, horses, pigs, ferrets and birds. These are the main source of human infections and are associated with epidemics and pandemics. There are 15 known haemagglutinin (H) serotypes and 9 known neuraminidase (N) serotypes. Pigs and birds are believed to be particularly important reservoirs for influenza virus, generating pools of genetically and antigenically diverse viruses which may be transferred back to the human population via close contact between humans and animals.
- Influenza B viruses only infect mammals and although they cause disease, this is not generally not as severe as that cause by influenza A viruses. Unlike influenza A viruses, influenza B viruses do not have distinguishable serotypes.
- Influenza C viruses also infect mammals only, but as far as is known, do not cause disease. They are also genetically and morphologically distinct from A and B types.
Influenza viruses replicate inside host cells. Entry into the cell occurs when haemagglutinin spikes on the outside of the particle bind to receptor on the surface of the cell. This interaction can be reversed by neuraminidase spikes, which prevents the virus getting stuck on the wrong cell type.
After binding, the particle enters the cell where the RNA genome segments make their way to the nucleus. There, the proteins they encode are transcribed and expressed by three polymerase polypeptides carried in the virus particle. New virus particles which form at the surface of the cell bud out through the cell surface membrane and search for new cells to infect. Influenza virus is highly infectious and is spread is by aerosols – coughs and sneezes spread diseases. When a person becomes infected, the virus kills the cells it infects in the nose and throat. The debris released by these cells causes to body to raise an immune response and this is responsible for the symptoms of influenza: fever, chills, muscle aches and headaches. Infections usually last from 3-7 days. Deaths directly from influenza infection are rare, but damage to the lining of the respiratory tract allows secondary bacterial infections such as pneumonia to occur, which with most strains of influenza account for most deaths.
Several anti-influenza drugs exist. Amantadine and rimantadine are active against influenza A viruses (but not B viruses). Newer drugs such as Tamiflu and Relenza inhibit the neuraminidase protein of the virus.
Influenza vaccines are produced in infected hens eggs or sometimes in cell cultures. The problem is that influenza virus is highly variable and its antigenic composition changes frequently due to genetic changes. These processes are known as antigenic drift and antigenic shift. A vaccine directed against one type of influenza virus (e.g. H3N2) does not protect against infection with a different antigenic type (e.g. H5N1).
The 1918 “Spanish flu” pandemic killed between 20-40 million people. Scientists believe that another influenza pandemic is now overdue and likely to occur soon. In May 1997, a three year-old boy infected with influenza virus died in the intensive care unit of a Hong Kong hospital. This case was the first isolation of an influenza A subtype H5N1 in a human. Subtype H5 influenza viruses can cause lethal avian influenza (bird flu), a disease which can decimate flocks of domestic poultry. H5N1 influenza re-emerged in Vietnam late in 2003 and since that time has spread to many areas of the world, although it is still primarily an avian virus. Also worryingly, in March 1999 H9N2 viruses were isolated from two hospitalized children in Hong Kong. At the present time we do not know what the source of the next human influenza pandemic will be, so we are unable to prepare suitable vaccines.