Photo Credit NIAID
# 8276
Not so very long ago, if someone spoke of `bird flu’, the understanding was they were talking about the H5N1 virus, which first appeared in Hong Kong in the mid-1990s. Sure, there were other avian influenza viruses – mostly low pathogenic (LPAI) varieties – that usually resided quietly in wild birds and waterfowl.
But H5N1, while only rarely jumping to humans, carried with it a staggering mortality rate (60% among known cases), and was considered the one to watch.
Along the way, we saw warning signs that other avian viruses might pose a threat, however. In 2007, in It Isn't Just Bird Flu, I wrote:
Other influenza viruses with pandemic potential exist out there, among them are H9N2, which infected two children in Hong Kong in 1999 and another in 2003, H7N7 which infected 89 people (1 death) in the Netherlands in 2003, and H10N7 which infected two infants in Egypt in 2004.
Beyond Influenza we also watch for SARS, which broke out of China in 2003, and infected 8000 people worldwide, killing roughly 800. SARS wasn't as easily transmitted as influenza, but it does have pandemic potential.
Since then, the list of novel flu viruses that could pose a public health threat has grown significantly, partly due to an increase in new reassortants, and partially due (I’m sure) to our ability to better detect new viruses.
Influenza A subtypes are categorized by two proteins they carry on their surface; their HA (hemagglutinin) and NA (neuraminidase). There are 17 known HA proteins, and 10 known NAs, making many different subtype combinations possible, although only a few are known to infect humans.
We also see variations within individual strains due to antigenic drift, which comes about when errors are made in the replication of the virus. Over a period of a few hours, millions of copies of a virus can be produced in a single host, and invariably some of these copies are `flawed’, and contain amino acid substitutions somewhere in the virus’s genetic code.
Most of the time, these changes either do nothing, or make the virus less viable. With millions of copies being generated, a few `duds’ hardly makes a difference to the virus, or the host.
But every once in awhile, out of millions of failures, a more biologically `fit’ virus will emerge. One that replicates better than either its parents or its siblings - and if it is also easily transmissible - it can take off as a new, emerging variant or (if it is genetically distinct enough) as a new clade.
And indeed, the H5N1 virus continues to produce new clades, and variations within those clades. The result that we are not just looking at one H5N1 virus in circulation, but dozens – each on its own evolutionary journey.
Since the H5N1 virus was first identified in 1996 it has expanded into more than 20 different clades and subclades, and various versions of the virus now circulate in different parts of the world (see Differences In Virulence Between Closely Related H5N1 Strains). You can see the evolution of the virus through 2011 in the chart below.
NOTE: Not all of these clades continue to circulate.
There are other H5 avian viruses of concern, including H5N2, H5N3, and the recently emerged H5N8 virus in Korea, which – for now, at least – only appears to infect poultry and wild birds.
Just about a year ago, the H7N9 virus appeared in China (although we did not learn of it until March 31st, 2013), a reassorted avian virus that owed much of its internal gene structure to the H9N2 virus. Since then, it has spread across eastern China, and jumped to humans, at a remarkable rate.
Reassorted viruses come about when a host (bird, swine, human, etc) is infected with two different influenza viruses that swap genes and produce a biologically fit hybrid.
This process is called Antigenic Shift, and it can result in an abrupt change in the behavior of a virus. While rare, as every virologist will tell you, Shift Happens.
This week alone we’ve seen published articles warning on the pandemic potential of the H10N8 virus, and a group of H6 avian viruses.
On Wednesday, in Lancet: Clinical & Epidemiological Characteristics Of A Fatal H10N8 Case, we looked at a report on the first known human infection with this novel avian virus, where the authors cautioned, `The pandemic potential of this novel virus should not be underestimated.’
And yesterday, the Journal of Virology ran a report called H6 influenza viruses pose a potential threat to human health, issuing similar warnings. CIDRAP NEWS summarized their findings last night in:
Study shows H6 avian flu may bind well to human cells
About a third of H6 avian flu strains tested were able to recognize human-type receptors, a sign that they may pose a threat to human health, according to a study yesterday in the Journal of Virology. The study also found that the strain replicated well in mouse lungs and transmitted fairly well among guinea pigs.
Chinese, Thai, and Japanese researchers, including Yoshihiro Kawaoka, DVM, PhD, who also has a lab at the University of Wisconsin, tested H6 viruses isolated from live-poultry markets in southern China from 2008 through 2011.
They found that, of 257 H6 strains tested, 87 (34%) recognized human-type receptors. Sequencing of 38 representative viruses revealed 30 different genotypes, "indicating that these viruses are actively circulating and reassorting in nature," the researchers wrote.
And indeed, last May in Taiwan CDC Reports Human Infection With Avian H6N1, we saw the first known H6 human infection.
So far, H10N8 and H6N1 have a minuscule track record when it comes to infecting humans, and so it is very difficult to gauge their true potential, particularly when you compare them to H7N9 and H5N1, which have infected hundreds of people.
Still, they bear watching.
Added to this rogues gallery of viral contenders, in the past year or so we’ve also looked at such unusual flu stories as:
Hong Kong: Isolation & Treatment Of An H9N2 Patient
China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs
mBio: A Mammalian Adapted H3N8 In Seals
PLoS Pathogens: New World Bats Harbor Diverse Flu Strains
And this is just a partial list, and doesn’t even touch on the swine varieties of influenza, or the constant evolution of seasonal flu strains.
While I can’t predict what any of these influenza viruses will do, it’s a pretty safe bet that we’re going to see more unusual flu viruses emerge over the next few years.Admittedly, most will probably only pose a limited threat to humans.
But their emergence should inspire governments, agencies, businesses, organizations, and communities to dust off, update, and test their pandemic preparedness plans (see DNI: An Influenza Pandemic As A National Security Threat & Pandemic Preparedness: Taking Our Cue From The Experts).
Because, honestly, it only takes one of these viruses to turn pandemic to ruin your entire day.
