April 30, 2013

Bird flu: to fear and not to fear
The Mix asked Ming Luo, Ph.D., professor in the Department of Microbiology to answer some common questions about bird flu.

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I find it frightening when new strains of bird flu emerge somewhere in the world. Perhaps it's the combination of having two boys, knowing enough science to realize that a global pandemic is possible and having seen too many disaster movies like Contagion, Children of Men and Outbreak.

greg h1n1 virusThe Wall Street Journal reports that, as of last Saturday night, there were 120 confirmed cases of the latest strain of bird flu, H7N9, which has caused 23 deaths so far in mainland China. Last week, the virus spread for the first time outside of the Chinese mainland, with one case diagnosed in Taiwan. The virus is probably just a few small changes away from becoming a global threat, and yet the chances of that happening are very small. It makes for an odd mix of comfort and dread.

The Mix asked Ming Luo, Ph.D., professor in the Department of Microbiology within the UAB School of Medicine, to answer some common questions about bird flu, and about why its jump from birds into humans makes it dangerous. He also updated us on his work seeking to design new drugs against flu viruses. Bottom line: a vaccine for the new bird flu would take 6-10 months to get ready, and new classes of antiviral treatments are years away. Researchers will probably one day come up with a vaccine that protects us against all flu viruses, but until then I get jumpy as each strain emerges.

Q. Why are bird flu viruses so deadly when they jump into humans?

A. When humans are infected by a virus from another species, the human immune system has had no chance to develop any immunity against it, said Dr. Luo. Our immune cells do not recognize the new invader,and so cannot quickly ramp up a massive counterattack against them. The new flu virus is also dangerous because it appears to make copies of itself very quickly once inside human cells, and to cause more severe lung damage than does a typical flu virus.

Q. What are the chances that the new virus becomes a global pandemic?

A. This new H7N9 flu virus is closer to a human flu virus than all previously known avian flu viruses, which makes it easier for the virus to jump from birds to humans, Dr. Luo said. Should a few more mutations, small random genetic changes, occur in the virus, it could result in a virus that is passed from person to person worldwide. The last such pandemic happened in 1918. That said, the spread of current H7N9 virus has largely ceased, or has at least greatly slowed down. In its current form, it is very unlikely to become transmissible from human to human, Dr. Luo said.

Q. Why are poultry versions of influenza viruses spreading now as opposed to 20 years ago?

A. Researchers see more cases of human infections by avian flu viruses because of increased density of the human population, more global travel and more consumption of live poultry in large cities in places like China.

Q. How would you rate the current government/health care surveillance systems designed to catch and isolate new cases of new flu viruses to prevent their spread? 

A. The global surveillance system worked very efficiently in this latest case. Within weeks of the first infection, the new H7N9 virus was identified, and the information was shared globally so that any new case could be identified around the world. Authorities in places like Hong Kong are shutting down and sterilizing live poultry markets, and health authorities are watching for and isolating cases.

Q. What kind of birds are spreading the virus to humans?

It looks like chickens as opposed to migrating birds, which are often the vectors that spread viruses through poultry populations.

Q. What advances have been made in the field that promise to deliver new treatments in time to prevent an influenza pandemic?

A. To develop a H7N9 vaccine will take 6-10 months, said Dr. Luo. There is always a long delay in developing a flu vaccine against a new strain. Preliminary efforts are underway to develop a universal flu vaccine, but it may take years.

A. Antiviral drugs will, in the future, represent another effective alternative to prevent and treat flu infection. Preliminary tests showed that this H7N9 virus is sensitive to currently available drugs in the class called neuraminidase inhibitors, including Tamiflu, Relenza and Peramivir, the latter of which was developed in a partnership between UAB and the company BioCryst. Many governments participate in antiviral drug stockpiling programs in case of pandemic infection.

Note: BioCryst and UAB have had a close relationship since BioCryst was founded. Former BioCryst CEO, Dr. Charles E. Bugg, was also a past director of the UAB Center for Macromolecular Crystallography. Former BioCryst CEO, Dr. J. Claude Bennett, was previously UAB President. Several of BioCryst's early drug development programs originated at UAB. Currently, BioCryst has research agreements in place with UAB focused on influenza neuraminidase and complement inhibitors.

Q. What is neuraminidase, and why do current antiviral drugs seek to inhibit it?


A. Neuraminidase is a viral enzyme located on the surface of flu virus particle. Neuraminidase inhibitors are drugs that bind to neuraminidase tightly and shut it down, which stops the ability of flu viruses to spread from cell to cell.

Q. I understand you are working to develop antiviral therapies that block the ability of influenza to fuse with and enter a human cell on the way to turning human cells into virus factories?  What progress are you making in that design effort, and what’s next?

A. Neuraminidase inhibitors target a viral protein called neuraminidase, but this protein regularly changes shape in quickly evolving viruses. These shape changes could eventually enable flu viruses with mutated proteins to become resistant to all current neuraminidase inhibitor drugs. Thus, the field is striving to develop drugs that target different viral proteins as a backup.  Dr. Luo's lab is working on fusion inhibitors that target a viral protein called hemagglutinin, and by blocking it, take away the ability of a virus to enter into human cells. In the lab, our fusion inhibitors block cell infection by many strains of influenza virus, including those already resistant to neuraminidase inhibitors. We are testing this class of novel inhibitors in animal studies.

Q. How would the viral fusion inhibitors you are working with complement neuraminidase inhibitors? 

A. Our studies already showed that influenza viruses that are resistant to neuraminidase inhibitors are sensitive to our fusion inhibitors. The two classes of inhibitors target two unrelated viral proteins so changes in one may not affect the other. When two drugs target a disease process via independent mechanisms, they can in some cases be combined in potent antiviral drug cocktails.

Note: the H7N9 name of the newly emerged bird flu strain refers to the versions of hemagglutinin (H) and neuraminidase (N) found to be specific to the virus, and more precisely, to the fragments of those proteins that trigger our immune systems to respond to them.

Q. How long before human testing can start with your clinical candidate drugs?

A. We are testing these fusion inhibitors in animal models now. If it works in an animal model, it will still take years before human testing can begin for the new drugs. We need to begin studies of new drugs long before new threats of pandemic flu appear.

For the most recent updates on bird flu, see the Disease Outbreak News bulletins from the World Health Organization.
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