/ 7 February 2004

Bird flu: The mutation risk

The big worry in the bird-flu scare is that the virus, at present a low-scale killer, could mutate into a pathogen that could claim millions of lives.

But how could this happen? And is it a serious risk? A virus is essentially a parasite: it enters a cell, hijacking its metabolic and reproductive machinery in order to replicate and to do this successfully it has to adapt to the creature it infects.

Most viruses do not mutate all that much — but influenza, like the human immunodeficiency virus (HIV), is a notorious exception.

”Influenza viruses have an inherently high rate of mutation, which means that they are very flexible genetically and can adapt to a new environment,” Maria Zambon, head of the flu laboratory at Britain’s Health Protection Agency, said in an interview.

Flu viruses mutate in two ways: a slow, low-key change that usually is a minor public-health problem; and a fast, highly important genetic transformation, which is the source of the alarm today.

The big leap, called a genetic reassortment, occurs when one type of virus swaps genes with a related virus.

That way it can gain characteristics that it did not have before, becoming able for instance to leap to other species, become more virulent or contagious.

At present, H5N1, the name for the bird-flu virus, is transmitted from poultry to humans — most likely through airborne faeces that carry the bug — but cannot be transmitted from humans to humans.

The big concern is that H5N1 would mingle with the ordinary flu virus, perhaps in someone who is suffering from influenza, or with an intermediary animal such as the pig, which can harbour both avian and human flu viruses.

That way, a mass killer could emerge: a virus that is both lethal and contagious.

A mutated bird-flu virus erupted among humans in 1918, killing as many as 40-million people, and lesser pandemics occurred in 1957 and 1968.

Ranged against H5N1, say virologists, are four genetic and environmental obstacles that discourage it from becoming established in a human population:

  • Its viral replication in human cells may be inefficient. There may be too few viral offspring emerging from infected cells to create a big ”viral load” that can be spread through coughing or sneezing, as the human flu virus does so well.
  • The avian virus is unable to lock on effectively to human cells, or more accurately certain types of human cells. The spike that enables it to lock on to the cell receptor is the wrong shape.
  • Avian viruses’ natural home is the gut of birds, where the temperature is a balmy 37 degrees Celsius. The human respiratory tract, though, is 33 degrees to 34 degrees Celsius. That coolness could have an impact on how well the virus reproduces.
  • Bird viruses are well adapted to evading the immune system of birds by skirting the molecular tripwires that unleash antibodies and white blood cells that destroy invaders. But they do not yet have this in humans.

For H5N1 to spread efficiently among humans, ”you are probably going to need changes in more than one gene”, said Zambon.

Given that the virus only has 10 genes, that might seem to be a major obstacle.

But Zambon is cautious, noting that very little is known about exactly which genetic changes can switch on a virus’ virulence.

”We’ve had the genetic sequence of the human influenza strain for over 30 years, and we still can’t work out, in a relatively small genome, what it is that’s important in causing people to die,” she said.

A 2000 study by United States-based researchers found that a specific strain of H5N1 that killed six out of 18 infected people in Hong Kong in 1997 had a few mutations in one gene, PB2.

Those tiny changes were enough to transform it into an extremely virulent agent.

”Because the influenza virus constantly mutates, and because only a few changes can make a non-pathogenic virus highly pathogenic, we should assume that an outbreak of any new strain or subtype is potentially dangerous to humans,” said lead researcher Yoshihiro Kawaoka. — Sapa-AFP