Monday, August 08, 2016

Emerg. Microbes & Inf.: Prevalence Of Influenza A in North Atlantic Gray Seals

Gray Seals - Credit Wikipedia


Aquatic birds are considered the natural reservoir for influenza A viruses.  Other species (intermediate hosts) like humans, pigs, and horses may contract and spread the virus, but in its natural host the virus is generally asymptomatic or mild.

With the exception of the recently discovered subtypes H17N10 and H18N11 in bats, all known subtypes of Influenza A have been detected in birds. 

Over the past dozen years our knowledge of the host range for influenza A has grown markedly, including two emerging canine flu (H3N8 & H3N2) viruses, H3N8 in camels, avian flu in tigers, Skunks and Rabbits with Avian Flu and several epizootics of influenza A in marine mammals (see PLoS One: Pathology Of A/H10N7 In Harbor Seals).

The seal outbreaks have been of particular interest as they've involved influenza subtypes (H7N7, H3N8, H10N7, H1N1) that have infected humans in the past, and in some cases they have shown signs of increased mammalian adaptations.  

Up until now, it has been assumed that marine mammals are an intermediate or `spillover' host for the influenza A virus - impacted much in the same way as humans, horses, and pigs.  

But we've new research, published this week in Emerging Microbes and Infections, that raises the intriguing possibility that Gray Seals might be a natural wild reservoir for the virus.

First a link, and the abstract, to the study.  Then I'll be back to discuss some of their findings.

Emerg Microbes Infect. 2016 Aug 3;5(8):e81. doi: 10.1038/emi.2016.77.

Prevalence of influenza A virus in live-captured North Atlantic gray seals: a possible wild reservoir.

Puryear WB1, Keogh M2, Hill N1, Moxley J3, Josephson E4, Davis KR1, Bandoro C1, Lidgard D5, Bogomolni A6, Levin M7, Lang S8, Hammill M8, Bowen D8, Johnston DW3, Romano T2, Waring G4, Runstadler J1.


Influenza A virus (IAV) has been associated with multiple unusual mortality events (UMEs) in North Atlantic pinnipeds, frequently attributed to spillover of virus from wild-bird reservoirs. To determine if endemic infection persists outside of UMEs, we undertook a multiyear investigation of IAV in healthy, live-captured Northwest Atlantic gray seals (Halichoerus grypus).
From 2013 to 2015, we sampled 345 pups and 57 adults from Cape Cod, MA, USA and Nova Scotia, Canada consistently detecting IAV infection across all groups. There was an overall viral prevalence of 9.0% (95% confidence interval (CI): 6.4%-12.5%) in weaned pups and 5.3% (CI: 1.2%-14.6%) in adults, with seroprevalences of 19.3% (CI: 15.0%-24.5%) and 50% (CI: 33.7%-66.4%), respectively. Positive sera showed a broad reactivity to diverse influenza subtypes.
IAV status did not correlate with measures of animal health nor impact animal movement or foraging. This study demonstrated that Northwest Atlantic gray seals are both permissive to and tolerant of diverse IAV, possibly representing an endemically infected wild reservoir population.

Essentially, they found a high level of influenza A infection in the sampled seal population, but with little or no sign of illness.  Grey seals - unlike the unusual mortality events with Harbor seals - appear to carry the virus without ill effect.

The authors write:

An in vivo study using experimental infection with a seal-derived H7N7 found that while harbor seals developed disease, gray seals and harp seals (Pagophilus groenlandicus) were resistant to disease,7 reminiscent of the low pathogenicity seen in avian natural reservoirs.15

Also impressive was the array of Influenza A viruses detected in this study.  Again from the study:

The most frequently recognized subtypes were pH1N1, seal H3N8, H13 and H16. However, a large proportion of seropositive pups recognized H6, adults frequently recognized H2N3, and animals from Sable Island had a strong response to H4N6. 

Nearly all animals tested recognized the seal-derived H3N8 that was identified during the 2011 UME in harbor seals in the Gulf of Maine. This strongly suggests that although gray seals were not impacted by the UME, they were likely exposed and either H3N8 specific antibodies have been maintained for 4 years or more, or the virus continues to circulate.

Also of particular interest, all groups of animals sampled on Cape Cod showed a moderate to strong reactivity against human pandemic H1N1; however animals from Sable Island did not. This is reminiscent of the recent report of the human population established pH1N1 infection found within northern elephant seals (Mirounga angustirostris) in California.2

Although the study is relatively small, and the results open to interpretation (you'll want to read the full report), the authors write:

Reservoir hosts are often defined as being a long-term host for a pathogen in which infection is well tolerated and maintained at a subclinical level.17, 18, 19
As a reservoir host does not typically show signs of disease, it provides a mechanism for the pathogen to be maintained and evolve, and from which spillover into new populations can occur. 

In contrast, a spillover host is typically exemplified by strong and acute immune activation, disease progression and morbidity or mortality.17 Ongoing endemic infection is a key indicator of a reservoir host, particularly when coupled with asymptomatic infection and minimal long-term fitness costs. 

Mammalian reservoir hosts are of particular importance in that they can provide a mixing vessel and/or source of mammalian adaptation for IAV. When avian-specific variants acquire the ability to infect mammalian hosts, either through incremental mutations, or genomic reassortments brought about by coinfection with multiple viruses, there is a risk for human pandemic infection.20, 21, 22 As epizootic instances become more frequent, understanding the dynamics involved in interspecies transmission becomes increasingly important.

While we have to use words like `may', and `possibly', and `could', this study suggests that Grey Seals might represent a natural mammalian reservoir for influenza A viruses.

The concern being that if they are a natural host, the viruses they carry have greater opportunities to evolve and accrue mammalian adaptations.

Evolutionary changes that could conceivably make it easier for one of them to someday jump to humans.