How bird flu infection is blocked by human cells decoded

Researchers have found how the bird flu virus, which kills 60 per cent of the people it infects, is blocked by human cells, an advance that may lead to better approaches for stopping the potentially pandemic disease.

The researchers from The Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC) in Germany have found a way to assess whether people who suddenly become infected with a bird flu virus represent the first signs of a large scale disease outbreak.

The study, published in the journal Nature Communications, noted that avian influenza A viruses (IAVs) -- such as H5N1, H7N9, and H5N6 -- are unable to transform infected human cells into effective virus factories since they do not produce enough of the matrix protein M1 following infection.

The researchers said the infectious agent requires this protein to export the many copies of its genetic material from the cell nucleus -- an essential process for building new viruses.

The study explained that each member of the IAV family is named after two prickly proteins on the virus'' surface.

One of the proteins is hemagglutinin (H), which enables the virus to infect human and animal cells where it can multiply, and the other is neuraminidase (N), which helps the virus'' offspring to extract themselves from the infected cell.

Citing waterfowls as an example, the researchers said, there are 16 known hemagglutinin subtypes and nine known neuraminidase subtypes, resulting in at least 144 possible H and N combinations for infecting this bird.

They added that these combinations in the viruses are constantly changing and adapting to new avian hosts - like chickens, and also mammals like horses, pigs, and humans.

"Hemagglutinin in humans and birds have a slightly different chemical structure, for example, which makes it more difficult for an avian influenza virus to infiltrate a human cell than a bird''s cell," explained study co-author Matthias Selbach from MDC.

The researchers infected sets of lab-grown surface cells from lungs, separately with a bird flu virus, and a human flu virus.

Then they measured the quantity of all newly produced proteins.

On finer analysis, the researchers found that much larger quantities of the matrix protein M1 was produced in the lung cells infected with the human virus.

They said the M1 protein is responsible for exporting the replicated viral genetic material -- RNA -- from the nucleus of the infected cells, and then assembling it with other newly produced viral proteins to form flu virus offspring.

The scientists then found that the RNA of bird flu viruses remained trapped in the nucleus of human cells they infected since these had too little M1 protein.

The genetic material of the bird flu virus was far less capable of breaking out of the cell nucleus than the RNA of the human flu virus, they said.

"How pathogenic an avian flu virus is and whether or not it has pandemic potential depends, of course, on many factors. A study on cell cultures cannot cover all these factors," Selbach said.

However, the researchers said it might be useful in the future to include an analysis of this RNA segment in the risk assessment of IAVs.