Friday, November 24, 2017

Nature Sci Rpts: H5N6 Viruses Exhibit Varying Pathogenicity & Transmissibility In Mammals

Horizontal Transmission Results - Credit Sci Rpts


One of the recurring themes in this blog is that while we talk about avian H5N6 (or H5N8, H5N1, or H7N9) as if they were single entities - in truth, each of these subtypes contains multiple (sometimes dozens of) genotypes - and within each of these genotypes can be numerous minor variants.
Novel flu viruses continually reassort, evolve, and reinvent themselves in the wild.  Which is why - over the past 14 years - the WHO has been forced to select three dozen different H5N1 candidate vaccine viruses (CVVs) just to keep up.
Avian viruses can be remarkably promiscuous, capable of churning out new genotypes - and occasionally new subtypes - with remarkable speed.  While many of these new iterations will fade into oblivion - unable to compete against more biological `fit' variants - the roster of viruses in circulation continues to expand. 
This diversity helps to explain how H5N1 has caused major outbreaks in humans in places like Egypt and Indonesia, yet India  - where the virus has also been rife - has never reported a human infection (see Differences In Virulence Between Closely Related H5N1 Strains).
The avian H5N6 virus, which emerged in the spring of 2014, has caused at least 18 human infections in China, with roughly 60% mortality. Yet, despite hundreds of outbreaks across South Korea, Japan, Taiwan, Vietnam, and the Philippines over the past year, none of those places have reported a human case. 
Additionally, China - which saw a surge of human infections in late 2015 and through most of 2016 - has gone nearly a year (until last week) without reporting a new case, despite numerous H5N6 outbreaks in poultry.
While the very good news to all of this is that not all HPAI H5 avian viruses are equally dangerous, the bad news is there are a great many variants of each subtype evolving in the wild, providing many more opportunities for a pandemic strain to emerge.

Today the Journal Nature has a fascinating (open access) report that compares three genetically similar, but behaviorally different, H5N6 viruses collected in Hubei Province, China. 
  • One of the variants (CK918) produced only minor physical effects on inoculated lab mice, and zero mortality, while two others (DK01 and CK165) produced rapid weight loss, and a high mortality rate. 
  •  In transmission testing (using guinea pigs) CK918 and DK01 did not appear to transmit via direct contact or aerosol route, but CK165 transmitted to 2 out of 3 guinea pigs via direct contact (but not aerosol).
While not nearly as dramatic of a finding as last month's announced ferret-to-ferret airborne transmission of avian H7N9 (see Cell Host & Microbe: HPAI H7N9 Lethality & Transmission In Ferrets), this nevertheless demonstrates a significant step towards mammalian adaptation of this particular H5N6 variant.

I've only posted some excerpts, so follow the link to read it in its entirety.

Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicities and Transmissibilities in Mammals

Zongzheng Zhao, Zhendong Guo, Chunmao Zhang, Lina Liu, Ligong Chen, Cheng Zhang, Zhongyi Wang, Yingying Fu, Jianming Li, Huabin Shao, Qingping Luo, Jun Qian & Linna Liu

Scientific Reports 7, Article number: 16280 (2017)
Received: 31 August 2017
Accepted: 08 November 2017
Published online:  24 November 2017


Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. 

The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the clade, and the NA genes were derived from H6N6 viruses.
These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. 

In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health


Since the first human H5N6 virus infection was reported in China1, H5N6 viruses have caused sporadic infections in humans; at least 17 human infections have been reported in China. The emergence of human H5N6 influenza virus infection has raised global concerns regarding potential threats to human health.
The first H5N6 virus was detected in mallards in North America in 19752. In the past, H5N6 viruses exhibited low pathogenicity and had little impact on the poultry industry and human health, including in Germany in 19843 and in Sweden in 20024. However, the recently emerged Asian H5N6 strain showed high pathogenicity, and a series of poultry outbreaks resulting from H5N6 recently occurred in China, Laos, Vietnam, Korea, and Japan5,6,7,8,9,10.
H5N6 initially arose from the reassortment of H5N1 and H6N6. The second reassortment may have occurred between H5N6 and ZJ-HJ/07-like H9N2 viruses11, which are similar to H7N912 and H10N8 viruses13. In 2015, the third reassortment was generated by a deletion in the NA protein at residues 59–69, resulting in novel H5N6 viruses that were more likely to cross species barriers to infect humans14.
Currently, H5N6 has replaced H5N1 as the dominant avian influenza virus subtype in poultry in southern China. Furthermore, H5N6 was also detected in migratory waterfowl prior to the first human case15,16. Migratory waterfowl, which transverse long distances, played a major role in the geographical spread of H5N6. Chickens and ducks functioned as “vessels” to deliver H5N6 from avian species to humans14,17, and H5N6 continued to evolve to adapt to mammals.
We recently isolated three H5N6 viruses from domestic ducks and chickens in Hubei province, China. However, the zoonotic capabilities and pathogenicities of H5N6 viruses in poultry remained unknown. In the present study, we used phylogenetic analysis and evaluated the receptor-binding properties, pathogenicities and transmissibilities of H5N6 viruses. These studies expand our understanding of the pathogenicity and transmissibility of H5N6 viruses and will aid in influenza pandemic preparedness efforts.


In this study, we found that the three H5N6 viruses exhibited different pathogenicities and transmissibilities in mammals. Each of the three H5N6 viruses acquired varying degrees of binding affinity for human-like receptors, and CK165 could transmit between guinea pigs by direct contact but not via aerosol.


In summary, three avian influenza H5N6 viruses exhibited varying degrees of affinity for human-type (α-2,6) receptors, replicated well in a mouse model, and one was capable of transmitting in guinea pigs by direct contact. Notably, H5N6 viruses have maintained their adaptation for mammals, and human isolates have been found to reassort with H9N2 viruses. Therefore, H5N6 viruses may become the next potential candidates for global dissemination.
         (Continue . . . .) 

For some more recent blogs on the evolution of avian H5N6, you may wish to revisit:

Study: Experimental Infection Of Dogs With HPAI H5N1 & HPAI H5N6
Virology: Five Distinct Reassortants of HPAI H5N6 In Japan - Winter 2016–2017

Arch. Of Virology: Novel Reassortant H5N6 Isolated From Cats - Eastern China
Emerg. Microbes & Inf.: Human Infections With A Novel Reassortant H5N6

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