Monday, July 30, 2018

BMC Vet.: Novel Reassortant H1N2 & H3N2 Swine Influenza A Viruses - Chile


As mentioned in yesterday's blog (see Michigan: Pigs At Fowlerville Family Fair Test Positive For Swine Flu) - while surveillance in most of the world is marginal at best - we know that many different variants of swine influenza circulate in pigs around the globe.
Nearly all of these viruses contain genetic contributions from swine, avian, and human flu viruses - aka are `triple reassortants' - and as they circulate and co-mingle in swine, they continue to evolve down numerous evolutionary pathways.
This was the process by which the last H1N1 pandemic virus emerged in 2009, and there is little reason to doubt it could happen again someday.  For this reason we pay particular attention whenever a swine flu virus shows an ability to jump to humans.

In the fall of 2011 a new strain of swine H3N2 appeared in American pigs. What set this virus apart from earlier swine H3N2 viruses was that it was a triple reassortant swine virus which had picked up (via reassortment) the matrix (M) gene from the 2009 H1N1 pandemic virus.

The CDC has speculated that:
`This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’CDC HAN 2012
Since then, swine viruses carrying the 2009 H1N1 M gene have become more common around the world, and we've seen this M gene turn up in other novel flu viruses as well (see Canine H3N2 Reassortant With pH1N1 Matrix Gene).

Increasingly, we're seeing novel swine flu viruses in the wild being described as `human-like', which arguably brings them closer to becoming a species jumping strain. From 2015's J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs.
The authors described both of these novel subtypes as “. . . virulent and can sustain onward transmission in pigs, and the naturally occurring mutations in the HA were associated with antigenic divergence from H3 IAV from human and swine’ and goes on to warn that  ``. . . the potential risk of these emerging swine IAV to humans should be considered”.
Also in 2015, in EID Journal: Influenza A Viruses of Human Origin in Swine, Brazil, we looked at surveillance in Brazil that uncovered multiple new lineages of swine influenza viruses that were related to seasonal influenza viruses that had circulated in humans more than a decade ago.
Three years ago, in Novel Human-like Influenza A Viruses Circulate in Swine in Mexico and Chile - published in PloS Currents - researchers reported finding:

Results: Our analysis identified multiple IAV-S lineages that appear to have been circulating undetected in swine for decades, including four novel IAV-S lineages of human seasonal virus origin that have not been previously identified in any swine populations globally.

We also found evidence of repeated introductions of pandemic H1N1 viruses from humans into swine in Mexico and Chile since 2009, and incursions of H1 and H3 viruses from North American swine into Mexico.
As the lines between human and swine flu viruses continue to blur, we have a new report - published last week in BMC Vet Research - that examines how these recently discovered human-like swine viruses isolated in Chile replicate in the guinea pig model.
Infection of novel reassortant H1N2 and H3N2 swine influenza A viruses in the guinea pig model

Rodrigo Tapia, Victoria García, Juan Mena, Sergio Bucarey, Rafael A. Medina and  Víctor Neira

Veterinary Research201849:73

© The Author(s) 2018

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. 

Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses. 

Influenza A virus (IAV) has economic and public health relevance, being considered ubiquitous in the swine industry worldwide [1, 2]. There was limited information about IAVs circulating in swine population around the world, but the pandemic H1N1 (pdmH1N1) lineage that emerged in 2009 underscored the need to increase the surveillance and research of IAV in swine (IAV-S) [3].

In Chile, novel IAVs-S of the H1 and H3 subtypes have been recently identified in commercial swine farms, which are genetically divergent from IAVs described in other countries. These novel IAV-S lineages were most closely related to human seasonal H1N1 and H3N2 viruses from the late 1980s and early 1990s and were named: Chile H1 human I, Chile H1 human II, Chile H3 human I, and Chile H3 human II [4]. 
To date, phylogenetic analyses have been based on hemagglutinin (HA) sequences only, highlighting the need for additional studies to fully characterize these viruses, including the evaluation of their zoonotic potential.
These results demonstrate that novel reassortant H1N2 and H3N2 IAVs-S with pandemic internal genes were able to infect, replicate and be shed efficiently in the upper respiratory tract of guinea pigs without prior adaptation. These viruses were compared with a pdmH1N1 virus, lineage that has been well studied in the guinea pig model since its emergence in 2009 [7, 8, 20]. 

Overall, all viruses had similar shedding kinetics except that both H1N2 viruses showed higher shedding titers than pdmH1N1 and H3N2 viruses. On the other hand, only animals inoculated with the H3N2 virus showed titers at 7 dpi. Using guinea pig model, Sun et al. [21] reported similar shedding kinetics for H1N2 and H3N2 IAVs-S isolated in 2006 in China and a pdmH1N1 virus isolated from human in 2009, where H3N2 IAVs-S took a longer time to clear from the nasopharyngeal cavity than pdmH1N1 and seasonal human viruses.

This is of importance, since the respiratory system of guinea pigs has anatomical and physiological characteristics comparable to those of humans [11] along with a similar IAV receptor distribution [21]. Hence, these results suggest that these novel reassortant IAVs-S might be capable of replicating efficiently in other mammal hosts, such as humans.
        (Continue . . . )

Admittedly, the primary thrust of this short report revolves around the advantages of using guinea pigs - instead of mice and ferrets - for characterizing novel flu swine flu viruses.

But it also provides us with a useful update on the 2015 Chilean swine flu report, and reminds us of the tremendous diversity of novel flu viruses that continue to circulate- and evolve - in swine herds around the globe.

For more on the swine-origin flu viruses, you may wish to revisit:
J. Virology: Pathogenesis & Transmission of H3N2v Viruses Isolated in the United States, 2011-2016
JVI: Divergent Human Origin influenza Viruses Detected In Australian Swine Populations
Emerg. Infect. & Microbes: Novel Triple-Reassortant influenza Viruses In Pigs, Guangxi, China

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