Eggshell Layer Makes Bird Virus Highly Infectious

Researchers have likely solved the mystery question of why human-to-human transmission of avian influenza viruses is much lower than from birds to humans. They discovered that in birds an eggshell-like mineral outer layer forms around the virus and provided an explanation of how this would increase the virus’ infectiveness.

The study, by researchers from Zhejiang University (Hangzhou, Zhejiang Province, China), also found that these mineralized viruses are more robust and heat stable than the native viruses.

Avian flu is a highly infectious disease among birds that has developed into a serious threat to human health. Close contact with diseased birds or their feces is considered to be the primary source of infections in humans. Transmission between humans is limited, however, which has indicated that these viruses cannot directly infect humans. Previously it was assumed that these viruses crossed the species barrier as a result of mutation, or recombination with DNA from another pathogen, but more recent results demonstrated that avian flu viruses isolated from infected humans have the same gene sequences as those from birds.

So how is it that humans catch the disease from birds? The researcher team, working with Dr. Ruikang Tang, professor at Zhejiang University, claims this is because the viruses acquire a mineral “shell” in the bird intestines. They discovered that viruses can become mineralized under calcium-rich conditions. Naturally, the digestive tract of birds—the primary location of avian flu viruses—provides just such a calcium-rich environment so that the birds can make eggshells. In humans, avian flu viruses infect the airways and are then found in bodily fluids, where the calcium concentration is too low for mineralization.

Experiments with a solution that imitates the bird intestine environment allowed the researchers to demonstrate that 5-6 nm thick shells of a calcium phosphate (CaP) mineral form around H9N2 and H1N1 viruses. In both cell cultures and mice, these mineralized viruses proved to be significantly more infectious and deadly than the native viruses.

The mineralized shell changes the electric surface potential of the viruses. This causes mineralized viruses to adsorb much more efficiently onto the surfaces of future host cells. The mechanism for uptake into the host is also different. Normally, the virus docks at receptors on the cell surface and is then brought into the cell. The mineral layer inhibits this—but clearly stimulates very efficient uptake on its own by mainly physical (physics-based) rather than chemical means. Furthermore: within the cell, the mineralized viruses enter into lysosomes, whose slightly acidic environment dissolves the mineral shell and releases the viruses.

This new information explains why humans are more likely to catch avian flu from birds than from their fellow humans, and may help in the development of new approaches to battling avian flu.

The study, by Zhou H et al, was published August 18, 2017, in the journal Angewandte Chemie International Edition.

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