The H7N9 Bird Flu is Highly Virulent, Mutates Fast, Research Suggests

As authorities report the arrival of H7N9 bird flu in central China, two new studies show that the virus can change quickly, and may be more infectious than previous strains.
The H7N9 Bird Flu is Highly Virulent, Mutates Fast, Research Suggests
A technician conducts tests at the Kunming Center for Disease Control in Kunming City, Yunnan Province, on April 10, 2013. (ChinaFotoPress/Getty Images)
4/14/2013
Updated:
4/14/2013

Two new cases of bird flu were reported in Henan Province on Sunday, bringing the number of people infected to over 50—13 of whom have died, according to state mouthpiece Xinhua—and marking the first occasion that the dangerously malleable virus has been reported to have spread to central China.

Chinese and international scientists have been busy studying the virus now that the entire genome has been sequenced. New research shows that H7N9 can change rapidly, potentially producing mutations that make it more infectious.

Scientists in Shenzhen found that a protein that binds H7N9 to its host’s cells could be mutating up to eight times faster than in a typical flu virus.

Dr. He Jiankui at South University of Science and Technology of China and colleagues found rapid mutation in hemagglutinin in one of the samples, with nine of 560 amino acids changed in a very short time period, compared with only one or two in a standard flu virus.

“It happened in just one or two weeks,” Dr. He told the South China Morning Post. “The speed may not have caught up with HIV, but it’s quite unusual for a flu.”

“We don’t know whether it will evolve into something harmless or dangerous,” Dr. He added. “Our samples are too limited. But the authorities should definitely be alarmed and get prepared for the worst-case scenario.”

In another paper, published in the New England Journal of Medicine, Chinese researchers described H7N9 as a “novel reassortant influenza A” virus with genetic similarities to strains found in three different birds–a Beijing finch, and ducks from Zhejiang Province and Korea.
 
The scientists are unsure how the new strain developed, as there is no evidence the reassortment took place in a mammalian host. Given the similarity of the human virus to the three avian strains, it is more likely to have been transmitted directly by birds.

Two of the three victims sampled were known to have had contact with live birds before they developed the disease. Although it causes little harm in poultry, the team noted that H7N9 can lead to “severe human infection,” with fever and coughing the most common early symptoms. The three Chinese later suffered acute respiratory distress syndrome, septic shock, and multiple organ failure.

As the virus shows no or only mild symptoms in birds, there is potential for “a ‘silent’ widespread epizootic [epidemic in animals] in China and neighboring countries,” wrote two flu scientists at the U.S. Centers for Disease Control and Prevention in an accompanying editorial.

They believe that H7N9 may be better adapted to infecting mammals than other bird flus, and say many experts are concerned that pigs could also be susceptible, thus acting as another reservoir for H7N9.

“Because this H7N9 virus has not been detected in humans or animals previously, the situation raises many urgent questions and global public health concerns,” they wrote.

A mutation called “Substitution Q226L,” found in two of the deceased, renders viruses more likely to infect ferrets, often used in flu research. This mutation also occurred in the viruses that caused flu pandemics in 1957 and 1968.

All three samples contained another mutation called “PB2 E627K,” which allows H7N9 to replicate in much cooler conditions than a standard bird flu, for example in the human respiratory tract, which is cooler than bird stomachs, where the virus is normally found.

Dutch virologist Ron Fouchier told CNN that this mutation in mice makes the disease up to 1,000 times more virulent. He believes that several other mutations present mean that the virus is not actually a bird flu. “Known normal bird viruses have to adapt substantially to infect people, but not these,” he said.

In the editorial, the U.S. researchers noted that the victims did not receive antiviral medication until the disease was well-developed, and earlier treatment could help prevent fatal secondary bacterial infections like pneumonia.

“The coming weeks will reveal whether the epidemiology reflects only a widespread zoonosis [infection between species], whether an H7N9 pandemic is beginning, or something in between,” they concluded.

“The key is intensified surveillance for H7N9 virus in humans and animals to help answer important questions. We cannot rest our guard.”

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