Wednesday, September 03, 2014

Nature Communications: Respiratory Transmission of Avian H3N8 In Ferrets


Photo Credit Wikipedia


# 9035


For those who aren’t completely overwhelmed by the plethora of zoonotic pathogens that have been coming out of the woodwork over the past few years, we’ve a new study today on an avian influenza virus – first isolated in New England seals back in 2011 (see New England Seal Deaths Tied to H3N8 Flu Virus)  –  that finds it is not only well adapted to mammalian hosts, that it can also be easily transmitted between ferrets via the respiratory route.

This H3N8 virus is of a different lineage than the Equine/Canine H3N8 virus, although they are cousins. 


Until it landed in seals, this H3N8 strain was an avian adapted virus.  That is, that it bound preferentially to the kind of receptor cells commonly found in the digestive and respiratory tracts of birds; alpha 2,3 receptor cells.


In 2010, in mBio: A Mammalian Adapted H3N8 In Seals, we saw the first hints that this virus had recently adapted to bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.

From the accompanying mBio press release New influenza virus from seals highlights the risks of pandemic flu from animals.


The mBio® study analyzed the DNA of a virus associated with a die-off of 162 New England harbor seals in 2011. Autopsies of five of the seals revealed they apparently died from infection with a type of influenza called H3N8, which is closely related to a flu strain that has been circulating in North American birds since 2002. Unlike the strain in birds, this virus has adaptations to living in mammals and has mutations that are known to make flu viruses more transmissible and cause more severe disease. The virus also has the ability to target a receptor called SAα-2,6, a protein found in the human respiratory tract.

Moscana says the study raises two concerns about flu. First, this strain is a novel virus that infects mammals and may well pass from animal to animal, a combination of traits that make it a potential threat to humans. Also, the possibility that a bird flu virus would infect seals hadn't been widely considered before, highlighting the fact that pandemic influenza can crop up in unexpected ways. She emphasizes the need for readiness.


Fast forward a couple of years, and today we have a study conducted by the USGS and St. Jude Children’s Research Hospital  appearing  in Nature Communications, that looks at the transmissibility of this emerging virus. 


In their words, they found  `the virus has an increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells.


A triple threat, in any league. And if that weren’t enough, testing of human sera for neutralizing antibodies finds little evidence of population wide immunity to this strain. 


All of this becomes even more concerning when you consider the history of H3N8 in humans.


The H3N8 virus is thought to have sparked the 1900 influenza pandemic. Since then it has continued to circulate in birds and pigs, and is considered a prime candidate to mount a return engagement someday again (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).


First the Abstract (the full article is behind a pay wall), then a press release with additional details from the USGS.


Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal

Erik A. Karlsson, Hon S. Ip, Jeffrey S. Hall, Sun Woo Yoon, Jordan Johnson, Melinda A. Beck, Richard J.  Webby & Stacey Schultz-Cherry Article number:


Published 03 September 2014

The ongoing human H7N9 influenza infections highlight the threat of emerging avian influenza viruses. In 2011, an avian H3N8 influenza virus isolated from moribund New England harbour seals was shown to have naturally acquired mutations known to increase the transmissibility of highly pathogenic H5N1 influenza viruses. To elucidate the potential human health threat, here we evaluate a panel of avian H3N8 viruses and find that the harbour seal virus displays increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells.

Analysis of a panel of human sera for H3N8 neutralizing antibodies suggests that there is no population-wide immunity to these viruses. The prevalence of H3N8 viruses in birds and multiple mammalian species including recent isolations from pigs and evidence that it was a past human pandemic virus make the need for surveillance and risk analysis of these viruses of public health importance.


From the USGS we have the following press release.



Avian Flu in Seals Could Infect People

Released: 9/3/2014 5:00:00 AM

Contact Information:
U.S. Department of the Interior, U.S. Geological Survey
Office of Communications and Publishing
12201 Sunrise Valley Dr, MS 119
Reston, VA 20192

The avian flu virus that caused widespread harbor seal deaths in 2011 can easily spread to and infect other mammals and potentially humans.

A new study by the U.S. Geological Survey and St. Jude Children’s Research Hospital shows that the avian influenza H3N8 strain that infected New England harbor seals could be transmitted to other mammals through the air without physical contact. Transmission by respiratory droplets through coughing, for example, is the main way influenza viruses spread among people. The study also showed that current seasonal flu vaccines do not protect against this seal virus, meaning a new vaccine would be necessary if there ever was an outbreak in humans.

"The ability to transmit through the air is an important step in the path toward any influenza virus becoming pandemic," said USGS scientist Hon Ip. "The lack of protection against the seal virus from the annual seasonal vaccine highlights the risks posed by this H3N8 group of viruses."

The article, led by St. Jude in collaboration with the USGS and the University of North Carolina at Chapel Hill, was published today in the journal Nature Communications and is available online.

The scientists tested a sample of the influenza virus taken from an infected harbor seal in New Hampshire in 2011, and found that the virus was closely related to influenza viruses from wild birds. However, the H3N8 virus isolated from the seal contained mutations that allowed it to reproduce efficiently in human lung cells, cause disease in mice and infect ferrets through the air.

"Findings from this study highlight the need for continued surveillance and study of avian influenza genetics, particularly in areas like coastal regions where wild birds, wild mammals and human populations come into contact with each other,” said USGS scientist Jeff Hall.

H3N8 viruses, common in wild birds, have been associated with ongoing outbreaks in dogs and horses and have also been detected in pigs, donkeys and now seals. Beginning in September 2011, more than 160 young harbor seals were found dead or dying along the New England coast as a result of this infection. In previous H3N8 mortality events, up to 20 percent of the local seal population died.

For more information on zoonotic diseases, or diseases that spread between animals and humans, please visit the USGS National Wildlife Health Center website.


Up until a few years ago most researchers would have said that birds and pigs are the most likely source of the next global health threat. Today, we look at bats, horses, dogs, camels and yes – even seals - as possibly sparking the next pandemic.


For more on the different strains of H3N8 (including canine and equine versions), and influenza in seals,  you may wish to revisit:


EID Journal: Equine H3N8 In Mongolian Bactrian Camel
Study: Dogs As Potential `Mixing Vessels’ For Influenza
The 2009 H1N1 Virus Expands Its Host Range (Again)