I just read an interesting article from the Max Delbruck Center for Molecular Medicine in the Helmholtz Association that explained why human cells are typically quite resistant to bird flu.
Bird flu (H5N1, H7N9, H5N6) does not readily spread between infected humans. In fact, most outbreaks involve only a handful to a few hundred individuals. But, on occasion, the infection can spread more easily leading to a pandemic. New research led by Dr. Matthias Selbach at the Center examined how the virus infects human cells.
There are actually 144 known possible combinations of bird flu as there are 16 hemagglutinin subtypes (the “H” in the name of the virus) and 9 neuraminidase subtypes (the “N”) known, at least in waterfowl. Suffice it to say that humans have only been infected with a handful of these combinations so far.
Dr. Selbach was quoted in the article, “Hemagglutinin in humans and birds has 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.” This quote came after research comparing infection of cells isolated from human lungs with bird flu versus a human flu virus. The research team found that while both viruses produced similar amounts of overall proteins, the human virus produced a lot more of the matrix protein, M1, compared to the bird virus. This protein is important for allowing the viral genes to exit the nucleus of cells and replicate. Confirming their suspicions that this might explain why human cells are not as susceptible to bird flu, they found that more of the genetic material (RNA) from the bird virus stayed in the nucleus of the cells compared to the human strain.
Boris Bogdanow et al. (2019): „The dynamic proteome of influenza A infection identifies M segment splicing as host range determinant“, Nature Communications, .