Sunday, January 14, 2018

Virology: The Zoonotic Potential Of Multiple Subgroups of Clade H5N8 Virus


Ever since clade H5N8 first emerged in South Korea as a major bird flu threat in January of 2014, many governments around the world have been quick to reassure that - unlike its cousins H5N1 and H5N6 - the H5N8 virus poses no threat to human health.
And while it is true we haven't seen a human infection with this particular subtype, past performance is never a guarantee of future results. 
The CDC's Influenza Risk Assessment Tool (IRAT) ranks H5N8 in the middle of the pack among the 14 novel viruses with pandemic potential they currently track, ranking its threat in the low-moderate range (less than 5).
H5N8: [A/gyrfalcon/Washington/41088/2014]
In December 2014, an H5N8 highly pathogenic avian influenza virus was first isolated from a sample collected in the United States from a captive gyrfalcon.Subsequently this virus was isolated from wild birds, captive wild birds, backyard flocks and commercial flocks in the United States.This virus (clade is similar to Eurasian lineage H5N8 viruses that have been isolated in South Korea, China, Japan, the Netherlands, the United Kingdom and Germany in late 2014-early 2015.There have been no reports of human cases.
Summary: The average risk score for the virus to achieve sustained human-to-human transmission was in the low-moderate range< (less than 5). The average summary risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission fell in the low-moderate range (less than 5).

This current lack of infectivity among humans, while welcome, may not last forever. Clade H5N6 has infected humans, and these HPAI H5 viruses have proven themselves to a promiscuous lot, reassorting at the drop of a gene segment, generating not only new genotypes, but new subtypes as well (see DEFRA: Update #12 On HPAI H5Nx In UK/Europe).

Over the past 12 months we've seen a number of studies that have looked at the potential for H5N8 or its spinoffs to evolve into a human health threat.  A few include:

J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade 
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions

Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice
Perhaps most telling of these came last September in J. Virulence : Altered Virulence Of (HPAI) H5N8 Reassortant Viruses In Mammalian Models, which found:
Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.
Last October, in J. Virulence Editorial: HPAI H5N8 - Should We Be Worried?
reviewed and summarized the literature, and found enough reasons to be concerned over the future evolutionary path of H5N8, stating that:

The extensive distribution of HPAI H5N8, as well as the gene reassortment with other circulating avian viruses already observed for H5N8 suggests there is a potential risk for human cases of H5N8 infections.
We've a new study, published in the journal Virology (alas, mostly behind a paywall) that finds some differences between distinct subgroups of H5N8 viruses isolated in South Korea.
While none were well adapted to human hosts, one (H2102) was a bit closer than the others.

First the abstract, then I'll return with a bit more.
Evaluation of the zoonotic potential of multiple subgroups of clade influenza A (H5N8) virus
Yu-Na Lee1, Eun-Kyoung Lee1, Byung-Min Song, Gyeong-Beom Heo, Sang-Hee Woo, Sun-Ha Cheon, Youn-Jeong Lee,  Show more rights and content


  • H2102 HPAIV (H5N8) caused relatively severe disease in mice at high doses.•
  • All H5N8 viruses replicated restrictively in the respiratory tract of ferrets.•
  • All H5N8 viruses displayed a HA phenotype that was poorly adapted to mammals.•
  • H2102 HPAIV (H5N8) showed higher replication kinetics at 33 °C than other strains.•
  • H5N8 HPAIVs have not yet acquired all features required for mammalian adaptation.

Clade H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs in South Korea; group A evolved further into four subgroups. 

Here, we examined the zoonotic potential, both in vivo and in vitro, of genetically distinct subgroups of H5N8 HPAIVs isolated in South Korea. 

When compared with other subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe disease in mice at high doses. In ferrets, all H5N8 viruses replicated restrictively in the respiratory tract and did not induce significant clinical signs of influenza infection.
In vitro studies, all viruses displayed a hemagglutinin phenotype that was poorly adapted for infection of mammals, although the H2102 virus exhibited higher replication kinetics at 33 °C than the others. 

Although H5N8 HPAIVs have not yet acquired all the characteristics required for adaptation to mammals, their ability to evolve continuously underscores the need for timely risk assessment.

Since clade H5N8 erupted on the Korean peninsula it has spread rapidly around the world via migratory birds (currently being reported in Africa, Russia, The Middle East, China and parts of Asia), and as it has, it has evolved (via reassortment) into scores of distinct genotypes, and has produced several new subtypes (H5N6, H5N5, H5N2, H5N1, etc.).
Other amino acid changes continue to occur -  due to antigenic drift or host adaptation - that futher propell these diverse H5N8 genotypes down their individual evolutionary pathways. 
While none of this means there is a human adapted H5N8 virus in our future, one can't ignore the possibility either. 

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