Chinese H7N9 Virus Making Its Way to Labs Around the World

The new H7N9 avian influenza strain that surfaced in China recently is now making its way around the world—not in humans, as far as anyone knows, but in carefully labeled, small packages sent from country to country and from lab to lab. Researchers at many institutes are still awaiting their own sample, eager to develop diagnostics and vaccines, gauge the virus’s potential to sicken animals and spread between them, and better understand its molecular makeup.

On Tuesday, the World Health Organization (WHO)—which nowupdates epidemiological info about H7N9 on Twitter first—reported three new infections with the virus and one death, bringing the total to63 cases and 14 deaths.

On Friday, WHO reported that the China Center for Disease Control and Prevention in Beijing had sent samples of the virus to all five of the so-called collaborating centers for influenza—a network of top influenza labs that work together with WHO—outside mainland China. These labs (in Tokyo, Melbourne, London, Atlanta, and Memphis) will carry out experiments themselves but are also responsible for distributing the virus further to other research labs and companies.

John McCauley, head of the collaborating center at the National Institute for Medical Research (NIMR) in Mill Hill, a suburb of London, says that he received the virus sample, named A/Anhui/1/2013, on Thursday, “packaged in multiple containers, all with secured screw tops.” It was contained in about half a milliliter of amniotic fluid, the liquid that surrounds an embryo in a hen’s egg.

In order to coax the virus into producing billions of copies, scientists use embryonated hen’s eggs that are 9 or 10 days old. The available eggs at Mill Hill were only 8 days old on Thursday and could have been difficult to infect, so scientists waited a day before seeding the virus. “Now we have 100 times the amount we were sent,” McCauley told ScienceInsider on Monday. Some of the produced virus was divided into small portions and labeled Monday evening; it will probably be sent out on Wednesday to the “more than 10 and fewer than 20″ labs that have requested it, McCauley says.

The U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, home to another WHO collaborating center, also received the virus on Thursday. Over the weekend, the virus was inoculated into hundreds of eggs, a CDC spokesperson says, in which it grew “very well.” On Monday, CDC began packaging virus samples in vials and sending them to other laboratories. Masato Tashiro, who heads a collaborating center at Japan’s National Institute of Infectious Diseases in Tokyo, says he hasn’t yet sent out any H7N9 samples.

One of the first experiments that the United Kingdom’s NIMR will conduct with the coveted virus is to put it in ferrets. Researchers will observe whether and how the virus sickens the animals, but the main point of the exercise is for the ferrets to develop antibodies, which can be harvested 2 weeks later, McCauley says. (If the virus causes very serious disease, scientists will give the animals antiviral medication to keep them alive.) The antiserum can be used to develop diagnostic tools; McCauley also wants to check whether the antibodies recognize candidate vaccine viruses against H7 flu strains that have been produced in the past.

Across the North Sea, virologist Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, says that he will also put the virus in ferrets as soon as his H7N9 shipment from NIMR arrives. One of the first things to study, besides pathogenicity, is whether the virus is “airborne,” Fouchier says—that is, transmissible through aerosols or tiny droplets between ferrets in adjoining cages. If it’s not, Fouchier says that he’s interested in finding out which mutations might make it easily transmissible between ferrets, the kind of experiments that raised a huge controversy when his lab reported them in H5N1. “It’s clearly a critical question,” Fouchier says, adding that the studies would first require extensive discussion.

Fouchier says that his group will also try to infect cynomolgus macaques, “because having two animal models is better than one.” Labs at the U.S. National Institutes of Health with which Erasmus MC collaborates may use other monkey models, such as rhesus macaques and African green monkeys, Fouchier says. “We usually coordinate in a situation like this.”

Establishing how serious a disease the virus causes in ferrets will be vital in later efforts to produce a vaccine, says Richard Webby, who heads the WHO collaborating center at St. Jude Children’s Research Hospital in Memphis, Tennessee, where the virus also arrived on Thursday. Vaccine manufacturers commonly use a virus constructed from the backbone of a less infectious flu strain together with the hemagglutinin and neuraminidase genes of the strain they want to make a vaccine against. “There will be a requirement to show that [vaccine strains] are attenuated compared to the wild-type virus,” Webby says. The early ferret experiments will help to show that.

The different WHO collaborating centers are duplicating some of the work on purpose, McCauley says. Unlike lab mice, ferrets are not inbred, genetically identical animals, and just like humans, different ferrets might react differently to the virus. “We do not want to rely on one or two animals in the whole world,” McCauley says.

Even without the real virus in hand, researchers have been able to experiment with a synthetic look-alike. Two days before he got the H7N9 sample, Webby had received a package in the mail from a company that produces genes on demand; they contained the hemagglutinin and neuraminidase genes, synthesized using the H7N9 sequences made available online by Chinese scientists. Stitching these genes into a standard lab strain called PR8 gives researchers an approximation of the actual virus and allows preliminary experiments, for instance to test if existing antibodies bind to the virus. Fouchier’s lab ordered the same two genes from what he calls a “phone and clone company.” But for pathogenesis and transmission studies, he says, “you really need the full virus.”

*Update, 10:40 a.m. on 17 April: A list sent to ScienceInsider by Yuelong Shu, director of the China CDC, shows that his agency has sent H7N9 not just to the WHO collaborating centers, but also to the National Institute for Biological Standards and Control in the United Kingdom, the Centre for Health Protection in Hong Kong, the Food and Drug Administration in the United States, and the Centers for Disease Control in Taiwan. “Any other institutes interested in the virus, please send a request to China CDC,” Shu adds in the e-mail.

Source: ScienceMag, ScienceInsider, by Kai Kupferschmidt and Martin Enserink, With reporting by Dennis Normile, 16/april/2013

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