How flu viruses change

The World Health Organisation has raised its global alert level, signalling the swine flu virus is spreading from human to human in community outbreaks. The threat of a global flu pandemic is growing. We take a look at how flu viruses change, leading to pandemics.

Swine influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.

The genetic make-up of influenza viruses A and B can and does change in two ways: a slight change known as antigenic drift and dramatic changes known as antigenic shift. Both result in new virus strains.

Like antigens of many other viruses, the surface proteins of flu viruses change periodically. These changes circumvent human antibodies and complicate vaccine development.

1. Small changes in the flu virus (antigenic drift)
Influenza A and B are classified by two surface antigens, haemagglutinin (H) and neuraminidase (N). These antigens are continually undergoing slight changes through what is technically known as antigenic drift. This is due to random copying errors in the viruses' genetic material during replication.

Persons with antibodies stimulated either by previous infection or vaccination are not protected from infection with new strains of the flu virus.

So despite a previous bout of flu, every year, but definitely every 3 years, the A and B viruses have changed sufficiently that they are no longer properly recognised by our immune systems, and one can be re-infected, with all the symptoms of flu again. This is why there are regular epidemics of winter flu.

2. Drastic changes in the flu virus (antigenic shift)
At irregular intervals of ten years or more, there is a drastic change in the influenza A virus when it replaces one of its genes with a new gene from a bird influenza virus. This is technically known as "antigenic shift".

Thus, when a gene of a bird influenza virus lands up in a human influenza virus, no human has appropriate immunity to this altered influenza A. The altered influenza A virus can be regarded as a "new" and very potent virus. A pandemic - a worldwide epidemic - of influenza will most probably follow.

The twentieth century saw pandemics of influenza A (as a result of antigenic shift) in:

  • 1918, known as the Spanish flu even though it originated from Boston (Look at a map to show the spread of the epidemic in South Africa),
  • 1957 (Asian flu),
  • 1968 (Hong Kong flu),
  • 1976/77 (Russian flu - the strain that caused this pandemic was identical to the one that circulated in the 1950's, and this pandemic primarily affected people younger than 25 years who had not been exposed to the 1950's flu virus), and
  • 1997 (Sydney flu).

Researchers have recently determined that the very virulent flu virus that caused the 1918 flu pandemic, was a H1N1 (where H1= hemagglutinin1, N1= neuraminidase1, two surface antigens) influenza virus. Virologists are still baffled why it caused such a severe pandemic - this remains a mystery. The closest known strain was Swine Iowa 30 - the pig flu virus isolated in 1930. Farmers in 1918 discovered that something was making their pigs very sick. Every autumn thereafter the American hog population got severe flu.

The virus probably came to people from pigs, not from birds. But research showed that the human viruses and the pig flu of 1930 may share a common avian ancestor. This suggests that sometime before 1918, a bird virus could have entered the pig population and, through reassortment, produced the pathogenic 1918 flu virus known to man.

This is how new pandemics will start: when parts of a bird virus get incorporated into a human virus, directly from a bird or via a pig.

The close proximity of humans, birds and pigs may enhance the possibility for this mixing of virus genes of different species.

A recent scare of a potential new killer virus
Small wonder that in 1997 Hong Kong doctors became frantic when they discovered that a 3-year old boy died from a pure avian virus against which most humans have no defense. It was a H5N1 avian virus, not readily transmittable, but if it reassorted with a common human strain it could have produced a new human influenza virus easily transmittable and very lethal.

In the end this avian virus infected 18 people and killed six, but luckily it did not lead to the birth of a new human influenza virus strain. This incident followed after 6 800 chickens died six months earlier on three farms in Hong Kong's rural territories, showing that this strain was deadly in birds.

This time it was not the start of a new epidemic.

The outbreak highlighted the success of the surveillance network. It also showed how dangerously mutable influenza viruses can be, and that they can be as deadly as Ebola or other killer viruses.

It is impossible to predict when the next pandemic will occur, but most scientists believe it is 100% certain that there will be one sometime.

In 1918, when transportation was still by rail and boat and painfully slow, the pandemic circled the globe in a matter of months. Travelling by jet, a new killer virus could circle the globe in 4 days, not 4 months as in 1918.

Flu pandemics then and now

 What happenedWhat could happen
World population1,8 billion6,7 billion
Primary mode of transportationTroop ship, railroadJets
Time for virus to circle globe4 months4 days
Preventative measuresGauze masks, disinfectantsVaccines (yet to be developed)
TreatmentsBed rest, aspirinSome antiviral drugs
Estimated death20+million60 million?

Read more:
Swine influenza
Save the Pigs!

Sources: AP, US Centers for Disease Control and Prevention (CDC)
Reviewed (2006) by Dr Jane Yeats MBChB, BSc(Med)(Hons)Biochem, FCPathSA(Virology).

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