H7N9 adaptation to humans – evidence for ongoing human to human transmission

From The University of Wisconsin-Madison News, April 12, 2013

A genetic analysis of the avian flu virus responsible for at least nine human deaths in China portrays a virus evolving to adapt to human cells, raising concern about its potential to spark a new global flu pandemic.

The collaborative study, conducted by a group led by Masato Tashiro of the Influenza Virus Research Center, National Institute of Infectious Diseases, and Yoshihiro Kawaoka of UW-Madison and the University of Tokyo, appears in the current edition (April 11, 2013) of the journal Eurosurveillance. The group examined the genetic sequences of H7N9 isolates from four of the pathogen’s human victims as well as samples derived from birds and the environs of a Shanghai market.

“The human isolates, but not the avian and environmental ones, have a protein mutation that allows for efficient growth in human cells and that also allows them to grow at a temperature that corresponds to the upper respiratory tract of humans, which is lower than you find in birds,” says Kawaoka, a leading expert on avian influenza.

[snip]

Although it is too early to predict its potential to cause a pandemic, signs that the virus is adapting to mammalian and, in particular, human hosts are unmistakable, says Kawaoka.

From CNN, April 12, 2013 [hat-tip, Pixie]

One concerning mutation, known as “Substitution Q226L,” was found in two of the first three victims. Past experiments have shown it to make viruses — including the H5N1 bird flu virus — more likely to infect ferrets, which are commonly used in flu research. The same mutation was also found in the viruses that caused the 1957 and 1968 flu pandemics.

A second mutation, known as “PB2 E627K,” was found in all three virus samples.

According to Dr. Ron Fouchier, a Dutch virologist, this mutation allows the virus to reproduce at much lower temperatures than a standard avian influenza virus. The change lets it grow in a human respiratory tract, which is cooler than the virus’ natural home: a bird’s gastrointestinal tract.

In mice, Fouchier said, the mutation makes the infection as much as 1,000 times more virulent.

A number of other mutations were found as well, including changes that are characteristic of viruses found in mammals.

“Known normal bird viruses have to adapt substantially to infect people, but not these,” said Fouchier, who said the changes are enough that he would no longer call the H7N9 strain “bird flu.”

For a virus to adapt to humans, such an adaptation must confer a selective advantage to the viruses tuned to infect humans rather than birds. The only way that I can see that happening is if the virus is being passaged from one human to the next. That would mean that the virus is likely already moving human to human. I would be interested if anyone can think of an alternative explanation for these results.

References

Eurosurveillance, Volume 18, Issue 15, 11 April 2013
Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013
T Kageyama, S Fujisaki1, E Takashita, H Xu, S Yamada, Y Uchida, G Neumann, T Saito, Y Kawaoka, M Tashir

New England Journal of Medicine, April 11, 2013
Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus
Gao et al.

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