Fu Virus binding to Receptor Cells – Credit CDC
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Although birds or pigs first come to mind when thinking about hosts for novel flu viruses in the wild, many other mammals are susceptible to infection (see Virology: Experimental Infection of Peridomestic Animals With Avian H7N9), including marine mammals like seals and whales.
These outbreaks likely happen more often than we know, but some documented examples include:
- During the winter of 1979-1980 seals were found suffering from pneumonia on the Cape Cod. In that instance, the culprit turned out to be an H7N7 influenza. (see Isolation of an influenza A virus from seals G. Lang, A. Gagnon and J. R. Geraci)
- In 1984 influenza subtype H4N5 – a strain previously only seen in birds – was determined to be behind the deaths of a number of New England seals in 1982 and 1983 (cite Are seals frequently infected with avian influenza viruses? R G Webster et al.)
- And in 1995, in the Journal of General Virology, authors R. J. Callan, G. Early, H. Kida and V. S. Hinshaw wrote of the The appearance of H3 influenza viruses in seals during the early 1990s.
- In November of 2011, we saw a die off of seals in New England that was eventually tied to an H3N8 avian Flu Virus. In 2012's mBio: A Mammalian Adapted H3N8 In Seals, we saw further evidence that this virus had recently adapted to better bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.
- In 2013 we saw a report (and a study) from UC Davis showing the human 2009 pandemic H1N1 virus had jumped to wild California Elephant Seals just one year after that virus emerged (see The 2009 H1N1 Virus Expands Its Host Range (Again)).
- And in 2017, during the HPAI H5N8 epizootic in Europe, that emerging subtype (clade 2.3.4.4.B) was found in Grey seals in the Baltic Sea (see EID Journal: Highly Pathogenic Avian Influenza A(H5N8) Virus in Gray Seals, Baltic Sea).
The biggest incident in recent memory, however, came in northern Europe (mostly Denmark and Germany & Sweden) in 2014, when as many as 3,000 harbor seals reportedly died from avian H10N7 (see Avian H10N7 Linked To Dead European Seals), prompting warnings to the public not to touch seals.
Although known human infections with avian H10N7 are limited, over the years a few have been documented.
- In 2004, the first known H10N7 human infections were reported among two Egyptian toddlers, as described in the WHO/CDS/CSR/RMD report Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt.
- And again, in 2012, in EID Journal: Human Infection With H10N7 Avian Influenza, we looked at a limited outbreak among workers with only mild symptoms at a chicken farm in Australia.
- While not H10N7, we saw three severe infections (2 fatal) with an H10N8 virus in China over the winter of 2013-2014.
Although the number of reported H10 infected humans remains small - possibly due to a lack of surveillance and testing - in 2014's BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China, we saw evidence that some people may have been infected with the H10N8 virus in China before the first case was recognized.
In the spring of 2019, in JVI: Aerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in Ferrets, we looked at research that found a `. . . . gull-origin H10N7 virus can be transmitted between ferrets through the direct contact and aerosol routes, without prior adaptation.'These researchers noted that these viruses `. . . showed high binding affinity to human-like glycan receptors. . . ', the authors recommended that avian H10 viruses be monitored closely, as they have some pandemic potential.
Of note, these gull-origin viruses were isolated in 2015, and showed genetic similarities to the H10N7 viruses that were isolated in the 2014 outbreak in Northern European seals.
All of which brings us to a new research paper - published yesterday in Cell Host & Microbe - that finds the avian H10N7 virus in the 2014 seal outbreak mentioned above adapted to its newly acquired mammalian host, allowing it to bind preferentially to α2,6-linked (mammalian) receptor cells, and to spread via respiratory droplets or aerosols among the seal population.
Follow the link to read the full study, as I've only included the abstract. A link, and some excerpts from the press release follow, after which I'll have a brief postscript.
ARTICLE| VOLUME 28, ISSUE 4, P602-613.E7, OCTOBER 07, 2020
Hemagglutinin Traits Determine Transmission of Avian A/H10N7 Influenza Virus between Mammals
Sander Herfst 5,Jie Zhang 5,Mathilde Richard, James C. Paulson , John J. Skehel, Ron A.M. Fouchier 8
DOI:https://doi.org/10.1016/j.chom.2020.08.011
Highlights
• Adaptation to seals led to transmission of avian A/H10N7 virus between mammals
• Three substitutions in HA altered receptor-binding preference and changed stability
• Receptor-binding specificity substitutions are located in the 220-loop of the HA
• A/H10N7 mammal transmission requirements resemble those for A/H5N1 and other viruses
Summary
In 2014, an outbreak of avian A/H10N7 influenza virus occurred among seals along North-European coastal waters, significantly impacting seal populations. Here, we examine the cross-species transmission and mammalian adaptation of this influenza A virus, revealing changes in the hemagglutinin surface protein that increase stability and receptor binding.
The seal A/H10N7 virus was aerosol or respiratory droplet transmissible between ferrets. Compared with avian H10 hemagglutinin, seal H10 hemagglutinin showed stronger binding to the human-type sialic acid receptor, with preferential binding to α2,6-linked sialic acids on long extended branches. In X-ray structures, changes in the 220-loop of the receptor-binding pocket caused similar interactions with human receptor as seen for pandemic strains. Two substitutions made seal H10 hemagglutinin more stable than avian H10 hemagglutinin and similar to human hemagglutinin.
Consequently, identification of avian-origin influenza viruses across mammals appears critical to detect influenza A viruses posing a major threat to humans and other mammals.
NEWS RELEASE 7-OCT-2020
A 2014 seal flu illustrates how avian flu viruses can adapt to spread between mammals
CELL PRESS
In 2014, an avian influenza virus caused an outbreak in harbor and gray seals in northern Europe, killing over 10% of the population. In a study appearing October 7 in the journal Cell Host & Microbe, researchers pinpoint the mammalian adaptation mutations that appeared during the outbreak in seals. They show that these mutations also made the virus transmissible via the air in ferrets and that similar mutations play a recurring and consistent role in making avian influenza viruses more transmissible between other mammal species.
"Usually, these occasional introductions of avian influenza viruses in seals, like in humans, are 'dead ends' because the virus is not transmissible from one individual to another," says first author Sander Herfst, an assistant professor of Molecular Virology and Virus Evolution at Erasmus MC. "However, sometimes these viruses adapt to the new host and acquire the ability to be transmitted between individuals."
The strain of avian influenza virus responsible for the outbreak, of the H10N7 subtype, first caused viral infections in harbor and gray seals along the coast of western Sweden and eastern Denmark in spring of 2014, killing more than 500 individuals. From there, it spread south toward the coasts of western Denmark and Germany, and finally the Netherlands, resulting in the death of an additional roughly 2,000 seals. Researchers believe the initial outbreak was likely caused by a seal coming into contact with birds or their droppings, but how it passed between seals is unknown.
"Transmission from seal to seal is likely to have occurred via aerosols or respiratory droplets, most probably whilst the seals are resting on land. However, direct contact transmission between seals can also not be excluded because seals are highly social and interact with each other regularly," says Herfst.
(SNIP)
In their investigations of the mutations to the seal virus and associated phenotypes that resulted in efficient transmission between ferrets, Herfst and his team found key mutations in the virus hemagglutinin--a protein on the surface of influenza viruses that plays an important role in binding to host cells. These changes, they say, affected the stability of the hemagglutinin and in addition led to the virus preferring to bind to mammal virus receptors in the respiratory tract, rather than avian. Interestingly, these hemagglutinin preference mutations occurred in viruses isolated in the late phases of the seal outbreak, suggesting that increased adaptation to a mammalian host occurred after the virus began its initial spread.
This is not the first time these kinds of mutations have been observed in influenza viruses. In fact, they have been present in prior pandemics. "The mutations that we identified are similar to the ones acquired in 1957 in the first year of the H2N2 pandemic in humans. In addition, these same mutations were required to render highly pathogenic avian influenza viruses of the H5N1 subtype transmissible via the air between ferrets--a model organism for mammal influenza research," Herfst remarks.
(Continue . . . )
H10N8: Avian H10N8 [A/Jiangxi-Donghu/346/2013]
Two human infections with influenza A(H10N8) virus were reported by the China Health and Family Planning Commission in 2013 and 2014 (one each year). Both cases were hospitalized and one died. Historically low pathogenic avian influenza H10 and N8 viruses have been recovered from birds. A risk assessment of the H10N8 influenza was conducted in 2014.Birds and pigs remain the most likely source of the next influenza pandemic, but there are dozens of species out there capable of serving as intermediate reservoirs - and possibly even `mixing vessels' - for novel flu strains.
Summary: The summary average risk score for the virus to achieve sustained human-to-human transmission was low-moderate (less than 5). The average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the moderate risk range (less than 7).
So, while a long shot, it is not beyond the realm of possibility that one or more could someday make the jump to humans.
A few (of many) past blogs on some of these `outlier' flu hosts include:
Back To The Bat Cave: More Influenza In Bats