To date, roughly 103 people have been infected with the H5N1 avian influenza virus--or bird flu. Yet few, if any, of them have spread the disease to other humans. A virus's ability to spread is the key to its ability to create a pandemic. New research shows that this bird flu currently lacks the protein key to unlock certain cells in the human upper respiratory tract, preventing it from spreading via a sneeze or a cough.

Virologist Yoshihiro Kawaoka of the University of Wisconsin and University of Tokyo and his colleagues tested strains of H5N1 isolated from respiratory tissue in the noses, throats and lungs of infected humans. Although regular human flu viruses bound easily with the receptors found in the nose and throat cells, H5N1 strains attached only to those receptors on cells found in the deepest regions of the lungs.

"Deep in the respiratory system, receptors for avian viruses, including avian H5N1 viruses, are present," Kawaoka explains. "But these receptors are rare in the upper portion of the respiratory system. 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."

Viruses require entry into such cells in order to replicate themselves and spread to yet more cells. Only one H5N1 strain--A/Hong Kong/213/03--showed the ability to latch onto either type of receptor and thus gain such access. The findings suggest one way in which H5N1 must mutate if it is to become a highly contagious virus, the researchers argue in their paper in today's Nature. It also reveals a way to monitor for the emergence of such a strain. "Identification of the H5N1 viruses with the ability to recognize human receptors would bring us one step closer to a pandemic strain," Kawaoka says. "Recognition of human receptors can serve as molecular markers for the pandemic potential of the [isolated strains]."