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New flu in China reveals its avian origins

H7N9 influenza genes came from three bird viruses

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A new type of bird flu that has killed 11 people in China combines genes from three existing influenza viruses, scientists report April 11 in the New England Journal of Medicine.

Since Chinese officials confirmed March 29 that three people had contracted H7N9 avian influenza, the virus has sickened 43 people. Of those still alive, many have severe illness, while others developed only mild symptoms. So far, the virus does not seem to spread from person to person, but health officials are closely watching more than 1,000 people who have been in contact with sick people for signs of illness.

The virus is a relative of ones found in birds, and some of the sick people had contact with poultry. But so far, health officials haven’t found the source of the infections.

Other avian influenzas, such as H5N1, are deadly to chickens and other birds. Poultry deaths give public health officials a head’s up on where human cases may appear, says Ana Fernandez-Sesma, a viral immunologist at Mount Sinai Hospital in New York. 

But a genetic analysis of the viruses isolated from the first three patients to contract the illness suggests why it has been difficult to find an animal reservoir: The virus probably doesn’t make birds sick. As a result, it spreads stealthily through poultry populations, study coauthor Rongbao Gao of the Chinese Center for Disease Control and Prevention and colleagues report.

By comparing the DNA of the viruses from the patients to other influenza viruses, the researchers discovered that this new H7N9 is a mix of three different bird flu viruses.

A protein called hemagglutinin (which gives the virus name its H), helps the virus grab on to cells in the respiratory tract. That protein most closely resembles that from an H7N3 virus isolated from a duck in China’s Zhejiang province, the researchers found.

The virus’s neuraminidase protein (the N in the name), which helps the virus escape from infected cells, is similar to those from an H7N9 virus in a Korean wild bird. Although the Korean bird virus is also an H7N9 virus, its hemagglutinin protein is quite different from the one found in the sick people.

The new virus’s remaining genes probably came from an H9N2 virus similar to one found in Beijing in finchlike birds called bramblings.

The three viruses could have infected a single bird and swapped genes, producing the new strain. Or the mixing could have happened in several steps. Such reassortments are common among influenza viruses and create new versions that host immune systems haven’t learned to fight. Mutations may then allow the bird viruses to infect mammals and to spread more easily.

The virus that infected the first patient, an 87-year-old man from Shanghai, has several mutations not shared by the viruses isolated from seven other people with the new flu. That may mean at least two versions of the virus have infected people.

But Fernandez-Sesma says there is not enough data to support the conclusion. “A bird doesn’t give you just one virus,” she says. “You have a cloud of viruses,” each with slightly different sets of mutations.

Particularly worrisome is that the version of the virus infecting all but the first Shanghai man contains a mutation that helped laboratory-created versions of another flu — the H5N1 virus that kills many people it infects but doesn’t spread person to person — able to spread through the air among ferrets. (Ferrets are often used as proxies for humans in infectious disease studies.) That mutation, known as Q226L, makes the virus better at grabbing human cells and has been found in naturally occurring pandemic strains.  The H7N9 virus also has other mutations that allow it to live in mammalian cells and some that render flu viruses more deadly in mice.

The mutations help explain why the virus is now able to infect humans, but the findings don’t mean that H7N9 is poised to become a pandemic strain, Fernandez-Sesma says. Other avian viruses carry similar mutations but don’t have the ability to spread easily from person to person. “It must be a really very hard property to acquire for avian viruses,” she says.

Because people have not contracted H7N9 before, most people in the world would probably harbor no immune protection and would be susceptible to the new virus, Timothy Uyeki and Nancy Cox of the U.S. Centers for Disease Control and Prevention write in an accompanying editorial. No vaccines are available, but the virus is susceptible to some antiviral drugs.

Note: This story was edited April 12, 2013, to update the death toll and H7N9 cases and to add additional comment.

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