Sunday, September 29, 2019

BioRxIv: Avian H3N8 With Multiple Mammalian-Adaptive Mutations in a Rescued Grey Seal


Human influenza pandemics over the past 100+ years are all believed to have stemmed from either H1, H2, or H3 viruses (see chart above). While the historical records suggest dozens of pandemics before that, those subtypes are lost to history.
The progression of human influenza pandemics over the past 130 years appears to have been H2, H3, H1, H2, H3, H1, H1 . . .
Although the next pandemic could break this repeating pattern - and come from an exotic avian H5, H7, or H10 virus - it makes sense to keep a close eye on the known repeat offenders.

H1, H2, and H3 viruses all circulate in birds, and somewhat infamously in swine, and are constantly evolving.  The 2009 H1N1 pandemic virus circulated in pigs for more than a decade before jumping species to spark the last pandemic. 
Other mammals host these subtypes as well, including dogs (H3N2 & H3N8) and horses (H3N8).
We've looked at the pandemic potential of both equine and canine influenza many times in the past, most recently:
EID Journal: Equine Influenza - A Neglected, Reemergent Disease Threat

Equine H3N8: Looking At A long-shot In The Pandemic Sweepstakes

Emerg. Microbes & Inf.: Genetic & Evolutionary Analysis of Emerging Canine H3N2

Emerg. Microbes & Infect.: Virulence, Transmissibility & Evolution of Canine H3N2 Influenza Viruses
While less well known, seals are also susceptible to a wide variety of influenza infection (see Emerg. Microbes & Inf.: Prevalence Of Influenza A in North Atlantic Gray Seals). 
These seal outbreaks have been of particular interest as they've often involved influenza subtypes (H7N7, H3N8, H10N7, H1N1) that have infected humans in the past, and in some cases the viruses they carry have shown signs of increased mammalian adaptation.   
Although the opportunities for human-seal contact are fewer than with canine or equine species, seals are far from a dead end host, making their suitability as a host for a pandemic virus of genuine interest, if not concern.
All of which brings us to a pre-print article in BioRxiv from earlier this month that looks at the detection of an avian H3N8 virus - with mammalian adaptations - in a rescued grey seal from 2017.

The full paper - which is very much worth reading - can be accessed at the link below.  I've only posted the Abstract.   I'll have a postscript when you return.
Detection of H3N8 influenza A virus with multiple mammalian-adaptive mutations in a rescued Grey seal (Halichoerus grypus) pup
Divya Venkatesh, Carlo Bianco, Alejandro Núñez, Rachael Collins, Darryl Thorpe, Scott M. Reid, Steve Essen, Natalie McGinn, James Seekings, Jayne Cooper, Ian H. Brown, Nicola S. Lewis
This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF


Avian Influenza A Viruses (IAV) in different species of seals display a spectrum of pathogenicity, from subclinical infection to mass mortality events. Here we present an investigation of avian IAV infection in a 3-4 month old Grey seal (Halichoerus grypus) pup, rescued from St Michael’s Mount, Cornwall in 2017.
The pup underwent medical treatment, but died after two weeks; post-mortem examination and histology indicated sepsis as the cause of death. IAV NP antigen was detected by immunohistochemistry in the nasal mucosa, and sensitive real-time reverse transcription polymerase chain reaction assays detected trace amounts of viral RNA within the lower respiratory tract, suggesting that the infection may have been cleared naturally. IAV prevalence among Grey seals may therefore be underestimated.
Moreover, contact with humans during the rescue raised concerns about potential zoonotic risk. Nucleotide sequencing revealed the virus to be of subtype H3N8. Combining a GISAID database BLAST search and time-scaled phylogenetic analyses, we inferred that the seal virus originated from an unsampled, locally circulating (in Northern Europe) viruses, likely from wild Anseriformes.
From examining the protein alignments, we found several residue changes in the seal virus that did not occur in the bird viruses, including D701N in the PB2 segment, a rare mutation, and a hallmark of mammalian adaptation of bird viruses. IAVs of H3N8 subtype have been noted for their particular ability to cross the species barrier and cause productive infections, including historical records suggesting that they may have caused the 1889 pandemic.
Therefore, infections such as the one we report here may be of interest to pandemic surveillance and risk, and may help us better understand the determinants and drivers of mammalian adaptation in influenza.
        (Continue . . . )

Most of the influenza's evolution goes on out of our sight, and without our knowledge.  Despite billions of attempts, nearly all of these genetic field experiments will fail, as most of these mutated viruses are unable to compete against established strains.
A few times each century, however, this rolling of the genetic dice produces a new, and biologically `fit' virus against which humans have little or no immunity, and another pandemic erupts. 
So obscure or not, we monitor emerging viruses like this one with considerable interest.