It is because bird flu viruses attach to receptors, or molecules on cells, in different regions of the respiratory system from human influenza viruses.

Receptors act like doorways that allow the virus to enter the cell, multiply and infect other cells. Humans have receptors for avian viruses, including H5N1, but they are found deep within the lungs.

Cells in the upper airway in humans lack the receptors targeted by avian flu viruses, which limit their ability to spread from person to person.

"For the viruses to be transmitted efficiently, they have to multiply in the upper portion of the respiratory system so that they can be transmitted by coughing and sneezing," said Dr Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison, who led the research team.

The H5N1 bird flu virus has killed 103 people and infected 184 since late 2003. People infected with the virus, which has spread from Asia to Europe, the Middle East and Africa, have had close contact with diseased birds.

Scientists fear the virus could mutate into a pandemic strain that could become highly infectious and capable of killing many millions of people.

"Our findings provide a rational explanation for why H5N1 viruses rarely infect and spread from human to human, although they can replicate efficiently in the lungs," Kawaoka and his team said in a report in the journal Nature.

MULTIPLE MUTATIONS

Professor John Oxford, a virologist at St Bartholomew's and the Royal London Hospital, Queen Mary's School of Medicine and Dentistry in London, said the research provides a reasonable explanation for the small number of human cases.

"This gives some meaning to the great conundrum at the moment, the fortunate conundrum of why this virus is not going from human to human," Oxford said in an interview

"It looks like a deep scientific study into that and we need more of those studies."

Kawaoka and a team of researchers in Japan infected human tissue with bird flu viruses. Their findings suggest that strains of H5N1 circulating in birds would have to undergo several key genetic changes to become easily transmissible in humans.

"The virus has to mutate to recognize human virus receptors which are in the throat," Kawaoka told Reuters.

"Certainly, multiple mutations need to be accumulated for the H5N1 virus to become a pandemic strain."

Scientists do not know how far the H5N1 has mutated to become a pandemic strain but Kawaoka's findings show the importance of looking for changes in virus recognition of human receptors.

The changes or mutations must occur in the hemagglutinin protein, the "H" in the virus designation, for avian H5N1 viruses to recognize human receptors, according to the researchers.

"Identification of H5N1 viruses with the ability to recognize human receptors would bring us one step closer to a pandemic strain," Kawaoka added.