18 June 2008
Avian Influenza Subtype H7 Has Pandemic Potential, Scientists Say
Highly pathogenic H5N1 avian flu still kills birds, people in some nations
Washington -- The most recently reported human case of highly pathogenic H5N1 avian influenza -- a 16-month-old boy from Dhaka in Bangladesh and that country’s first confirmed human infection -- brings total cases since 2003 to 383, with 241 deaths.
The child survived and human infection seems to be slowing in most countries, but the virus still is taking a toll among wild and domesticated birds. According to Animal Health Status Worldwide in 2007 and Early 2008, a report from the World Organisation for Animal Health (OIE) in Paris, 61 countries or territories reported H5N1 infections in birds between 2003 and May 2008.
“In 2008 (up to the end of May),” the report reads, “12 countries/territories had notified the reoccurrence of [highly pathogenic avian influenza] subtype H5N1 following its previous eradication, thus indicating that the virus is continuing to circulate.”
No other epizootic -- an epidemic among animals -- has lasted so long, OIE said in the report, or spread so far, so fast. But H5N1 is not the only avian flu virus subtype that could pose a long-term threat to birds and people.
“H5 and H7 subtypes are highly lethal in poultry,” Terrence Tumpey, senior microbiologist in the influenza division at the U.S. Centers for Disease Control and Prevention (CDC), told America.gov.
“There are low-pathogenic versions in this group,” he added, “but they also have the ability to mutate to high-pathogenic forms that are lethal for poultry. And, of course, it’s the H5N1 subtype viruses in Asia that are jumping from poultry to humans.”
H5N1 has been the subject of intense research around the world, Tumpey said, “but far less is known about the H7 virus infection in humans and the potential of this subtype to cause a pandemic.”
Before 2002, only a few H7 flu cases were documented in people, he said. Since 2002, several H7 outbreaks have occurred in poultry in the United States (H7N2, single case), Canada (H7N3), the United Kingdom (H7N2) and the Netherlands (H7N7), resulting in 100 confirmed cases of H7 flu in people and one death.
A May 27 study by Tumpey, Jessica Belser of CDC and Emory University in Georgia, and colleagues, published in the Proceedings of the National Academy of Sciences, describes how some North American H7 flu viruses have acquired properties that closely resemble human flu viruses and potentially could spread to animals that do not have immunity to the viruses.
FLU VIRUS ABCs
There are three types of flu viruses -- A, B and C. Influenza viruses can infect people, birds, pigs, horses, seals, whales and other animals, but wild birds are their natural hosts. “A” type viruses mutate much faster than B and C types, so they are divided into subtypes based on two proteins on the virus surface -- hemagglutinin (HA) and neuraminidase (NA).
There are 16 HA subtypes and nine NA subtypes, and subtypes are named according to their HA and NA surface proteins. The letters H and N in subtype names like H5N1 or H7N2 refer to these proteins.
In the body, flu viruses attach to host cells in the respiratory system when the HA protein binds to one of two forms of a chemical called sialic acid (SA) -- alpha 2-3 SA or alpha 2-6 SA.
“Sialic acid is basically just sugars linked to each other,” Tumpey said, “and they’re either linked in a 2-3 fashion or a 2-6 fashion. It’s just little differences in the linkage that allows the virus to attach to our respiratory cells.”
According to the study, avian flu viruses mainly bind 2-3 linked SA, and human viruses bind 2-6 SA. The three flu viruses that caused pandemics in 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2) each had an HA with a 2-6 binding preference, even though scientists think those viruses originated from avian (2-3) viruses. Seasonal flu also binds alpha 2-6.
H7 STUDY
From an evolutionary standpoint, Tumpey said, “influenza has been happy living in the guts of migratory birds and binding to 2-3. You can think of human infections as a mistake, really. We’re considered aberrant hosts because the virus is coexisting in the guts of migratory birds and the problems start when it gets out.”
When avian flu begins infecting new hosts like domesticated bird species, it can change. When it moves into people, it can change again.
“The virus makes mistakes when it replicates,” Tumpey said, and if it changes enough it could turn into an alpha 2-6 binding type virus, which is “present predominantly in our upper respiratory tract. [People] have very little alpha 2-3. So if a virus decides to make that receptor switch and recognize the 2-6, we think it might spread more efficiently.”
In their study, Tumpey, Belser and colleagues did two main things -- they examined the virus 2-3 and 2-6 binding properties, and they used ferrets to see how well the H7N2 virus could spread from an infected animal to an uninfected animal. They found the virus was transmissible by direct contact, and suggested that strong alpha 2-6 binding is an essential component of transmissibility in human flu viruses.
The finding was important because avian flu virus subtypes, including H5N1, are transmitted only by direct contact and not through the air.
Most scientists, Tumpey added, believe that characteristic has to change -- that a virus must be easily transmissible, through the air, from person to person -- before it can cause a pandemic.
Tumpey said more research is needed to assess the pandemic potential of H7 flu viruses.
The full text of the study of North American influenza viruses is available at the Proceedings of the National Academy of Sciences Web site.
