Thursday, May 16, 2013

The 2009 H1N1 Virus Expands Its Host Range (Again)



Credit Wikipedia



# 7279


While we wait for the next shoe to drop with nCoV and H7N9, there are other infectious disease related stories of note – including a UC Davis study, published yesterday in PLoS One, that finds the 2009 H1N1 influenza virus managed to jump to aquatic mammals.


As you’ll see, this isn’t the first time that marine mammals have been infected with influenza - but this time - there is considerable mystery attached to how they came to be infected.


While we normally think of birds, pigs and humans (and less commonly, horses and dogs) as the normal hosts of influenza viruses, there are other species that have shown the ability acquire and potentially spread certain strains of the virus as well.


The (formerly) pandemic H1N1 2009 flu virus has been documented in humans, swine, turkeys, skunks, ferrets, cats, and dogs. While in That Touch Of Mink Flu I wrote about 11 farms in Holstebro, Denmark that were reported to be infected with a variant of the human H3N2 virus.


Less commonly reported - camels, whales and seals have all been shown to be susceptible to influenza viruses (cite Evolution and ecology of influenza A viruses R.G. Webster et al.)


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.


Seals have also been shown susceptible to influenza B (cite Influenza B virus in seals. Osterhaus AD, Fouchier , et al.).


And more recently, in November of 2011 concerns were raised over the discovery that an influenza A strain  – (eventually identified as avian H3N8) – was infecting and killing seals in New England (see mBio: A Mammalian Adapted H3N8 In Seals).


So there is ample precedent for finding influenza viruses in marine mammals, but this marks the first time that a human pandemic strain has been found in one. 


Given that Elephant seals can reach colossal size (bulls can exceed 14ft in length and 5,000 lbs), they can be territorial and aggressive, and they spend 80% of their lives at sea, these marine mammals have very few opportunities for direct human contact.


Which leads to the question of just how these seals managed to acquire the virus?


First a link to the open access study, then some excerpts from the UC Davis press release, then I’ll be back with a little more.


Research Article

Pandemic H1N1 Influenza Isolated from Free-Ranging Northern Elephant Seals in 2010 off the Central California Coast

Tracey Goldstein equal contributor mail, Ignacio Mena equal contributor, Simon J. Anthony, Rafael Medina, Patrick W. Robinson, Denise J. Greig, Daniel P. Costa, W. Ian Lipkin, Adolfo Garcia-Sastre, Walter M. Boyce


Interspecies transmission of influenza A is an important factor in the evolution and ecology of influenza viruses. Marine mammals are in contact with a number of influenza reservoirs, including aquatic birds and humans, and this may facilitate transmission among avian and mammalian hosts.

Virus isolation, whole genome sequencing, and hemagluttination inhibition assay confirmed that exposure to pandemic H1N1 influenza virus occurred among free-ranging Northern Elephant Seals (Mirounga angustirostris) in 2010. Nasal swabs were collected from 42 adult female seals in April 2010, just after the animals had returned to the central California coast from their short post-breeding migration in the northeast Pacific. Swabs from two seals tested positive by RT-PCR for the matrix gene, and virus was isolated from each by inoculation into embryonic chicken eggs. Whole genome sequencing revealed greater than 99% homology with A/California/04/2009 (H1N1) that emerged in humans from swine in 2009.

Analysis of more than 300 serum samples showed that samples collected early in 2010 (n = 100) were negative and by April animals began to test positive for antibodies against the pH1N1 virus (HI titer of ≥1:40), supporting the molecular findings. In vitro characterizations studies revealed that viral replication was indistinguishable from that of reference strains of pH1N1 in canine kidney cells, but replication was inefficient in human epithelial respiratory cells, indicating these isolates may be elephant seal adapted viruses.


Thus findings confirmed that exposure to pandemic H1N1 that was circulating in people in 2009 occurred among free-ranging Northern Elephant Seals in 2010 off the central California coast. This is the first report of pH1N1 (A/Elephant seal/California/1/2010) in any marine mammal and provides evidence for cross species transmission of influenza viruses in free-ranging wildlife and movement of influenza viruses between humans and wildlife.

From UC Davis, a link to a press release, and a few excerpts.


H1N1 discovered in marine mammals

May 15, 2013

Scientists at the University of California, Davis, detected the H1N1 (2009) virus in free-ranging northern elephant seals off the central California coast a year after the human pandemic began, according to a study published today, May 15, in the journal PLOS ONE. It is the first report of that flu strain in any marine mammal.


“We thought we might find influenza viruses, which have been found before in marine mammals, but we did not expect to find pandemic H1N1,” said lead author Tracey Goldstein, an associate professor with the UC Davis One Health Institute and Wildlife Health Center. “This shows influenza viruses can move among species.”




“H1N1 was circulating in humans in 2009,” said Goldstein. “The seals on land in early 2010 tested negative before they went to sea, but when they returned from sea in spring 2010, they tested positive. So the question is where did it come from?”

(Continue . . . )


For now that question remains unanswered. 


There is speculation that seabirds might have carried the virus from land out to sea where these seals may have been exposed, or that discharge from cruise ships may have been involved. 


But these are merely guesses.


As to why this might be important?  


Regular readers of this blog are aware that avian influenza strains bind preferentially to the kind of receptor cells commonly found in the digestive and respiratory tracts of birds; alpha 2,3 receptor cells.


Human (and mammalian adapted) influenzas – on the other hand - bind to the kind of receptor cells that line the surfaces of the human upper respiratory system; alpha 2,6 receptor cells.


It turns out that some seals – like pigs – have both types of receptor cells (cite).


If infected by two different strains simultaneously, they could potentially act as a `mixing vessel’ for influenza strains, and produce a hybrid (reassorted) virus. 




The operative word being `potentially’. No one really knows how big a threat any of this really poses. We’ve no evidence of any influenza epidemic ever originating from aquatic mammals.


But the authors of yesterday’s study – via the press release – warn:


The findings are particularly pertinent to people who handle marine mammals, such as veterinarians and animal rescue and rehabilitation workers, Goldstein said.


They are also a reminder of the importance of wearing personal protective gear when working around marine mammals, both to prevent workers’ exposure to diseases, as well as to prevent the transmission of human diseases to animals.


With each passing year we learn more about about just how versatile, variable, and incredibly adaptable influenza viruses really are.


A trend that virtually guarantees plenty of avenues of new research for years to come.