Avian Flu Diary: Study: Pathogenicity and Transmissibility of Clade 2.3.4.4h H5N6 Avian Influenza Viruses in Mammals

#17,112

There are likely more cases than have been officially acknowledged, but the Chinese government reports 81 human infections with the avian H5N6 virus since 2014 (see above map), of which more than 2/3rds have occurred over the the past 24 months.

Long-term outcomes are rarely reported, but a significant portion (> 30%) of these infections appear to have been fatal, making H5N6 one of the deadlier avian flu viruses we've seen.

Despite linking most human H5N6 infections to contact with infected poultry, China has not reported a concurrent jump in H5N6 outbreaks in poultry. Admittedly, getting timely reports from China on disease outbreaks - in humans, wild birds, or poultry - has always been difficult.

Ineffective poultry vaccines (see EID Journal: Novel Reassortant Avian Influenza A(H5N6) Virus, China, 2021), however, may be allowing the virus to spread asymptomatically in poultry, where it continues to evolve, and occasionally spills over into humans.

Not all avian H5N6 viruses are able to infect, or sicken, mammals (including humans) (see Nature Sci Rpts: H5N6 Viruses Exhibit Varying Pathogenicity & Transmissibility In Mammals). But several subclades can, and the virus continues to evolve, primarily through reassortment.

In September 2021 the CCDC Weekly published a new study looking at two human H5N6 infections last year in Guangxi Zhuang Autonomous Region, which occurred 6 months apart (Feb. & July).

Both viruses were of different subclades (2.3.4.4h & 2.3.4.4b), were the product of recent (and different) ressortments, and showed worrisome mutations which could increase their threat.

Due to this recent increased level of H5N6 activity in China, the world has taken notice (see CDC Adds A New H5N6 Avian Flu Virus To IRAT List, WHO: Assessment of Risk Associated with Influenza A(H5N6) Virus and UK HSA Risk Assessment On HPAI H5N6).

Today we've a new study from Chinese researchers on the continued evolution, and increasing threat, of avian H5N6 clade 2.3.4.4h in China. I've only included some excerpts from a much longer report, so follow the link to read it in its entirety.

Pathogenicity and Transmissibility of Clade 2.3.4.4h H5N6 Avian Influenza Viruses in Mammals
by
Cheng Zhang 1,2,†,Huan Cui 2,3,†,Chunmao Zhang 2,Kui Zhao 3,Yunyi Kong 2,Ligong Chen 1,Shishan Dong 1,Zhaoliang Chen 1,Jie Pu 2,Lei Zhang 2,Zhendong Guo 2,* and Juxiang Liu 1,*

Academic Editors: Elena Catelli, Caterina Lupini and Giulia Mescolini
Animals 2022, 12(22), 3079; https://doi.org/10.3390/ani12223079
Received: 26 August 2022 / Revised: 2 November 2022 / Accepted: 8 November 2022 / Published: 9 November 2022

Academic Editors: Elena Catelli, Caterina Lupini and Giulia Mescolini
Animals 2022, 12(22), 3079; https://doi.org/10.3390/ani12223079
Received: 26 August 2022 / Revised: 2 November 2022 / Accepted: 8 November 2022 / Published: 9 November 2022
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Simple Summary
In the past decade, the spread of H5N6 avian influenza viruses (AIVs) in birds and infection in humans has attracted increasing global attention, and these viruses have the potential to become a pandemic threat to global health. In this study, the HA genes of the HB1907 and HB1905 AIVs were clustered in the 2.3.4.4h clade, and the HA genes of both strains exhibited highly pathogenic avian influenza virus (HPAIV) characteristics.

The HB1905 strain in this study has a binding preference for avian-like (α-2,3) receptors only, whereas the HB1907 strain has a binding preference for both avian-like (α-2,3) and human-like (α-2,6) receptors. Compared with the HB1905 strain, the HB1907 strain showed better replication ability in MDCK cells in the early stage of infection. At the same time, the HB1907 strain showed advantages in the pathogenicity of mice and the transmission ability of direct contact between guinea pigs. These results further suggest that epidemiological surveillance and the related studies of H5N6 AIVs are essential for public health safety and the healthy and sustainable development of the livestock industry.
Abstract

Avian influenza viruses (AIVs) have the potential for cross-species transmission and pandemics. In recent years, clade 2.3.4.4 H5N6 AIVs are prevalent in domestic poultry, posing a threat to the domestic poultry industry and public health.

In this study, two strains of H5N6 AIVs were isolated from chickens in Hebei, China, in 2019: A/chicken/Hebei/HB1907/2019(H5N6) and A/chicken/Hebei/HB1905/2019(H5N6). Phylogenetic analysis showed that both viral HA genes clustered in the 2.3.4.4h clade. Receptor binding analysis showed that the HB1905 strain preferentially binds to α-2,3-linked sialic acid (SA) receptors, while the HB1907 strain preferentially binds to α-2,3- and α-2,6-linked sialic acid (SA) receptors.

During early infection, the HB1907 strain is highly replicable in MDCK cells, more so than the HB1905 strain. Pathogenicity assays in mice showed that both viruses could replicate in the lungs without prior adaptation, with HB1907 being more highly pathogenic in mice than the HB1905 strain. Significantly, both the HB1905 and HB1907 strains can be transmitted through direct contact among guinea pigs, but the transmission efficiency of the HB1907 strain through contact between guinea pigs is much greater than that of the HB1905 strain. These results strengthen the need for ongoing surveillance and early warning of H5N6 AIVs in poultry.

(SNIP)

5. Conclusions

In conclusion, the two strains of H5N6 AIVs from the same branch in this study showed differences in mammalian models. We speculate that this difference may be caused by differences in amino acid mutation sites. Further studies are needed to investigate these findings, along with the biological roles of amino acid mutation sites. At the same time, the HB1907 virus in this study is highly replicated in MDCK cells, is highly pathogenic to mice, and has good direct contact transmission ability between guinea pigs.

These results further suggest our long-term epidemiological surveillance of H5N6 AIVs and related research. It is beneficial to human public health security and the healthy and sustainable development of animal husbandry. Research in mammalian models broadens our knowledge of chicken-origin H5N6 AIV clade 2.3.4.4h.

(Continue . . . )

Of the 23 novel viruses on the CDC's IRAT list of novel flu viruses with pandemic potential, 8 involve avian HPAI H5Nx viruses. But whether they are capable of sparking a pandemic in humans, the jury is still out.

And as we've discussed many times over the past few years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . . .

Simply put, novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans. That doesn't mean that an H5 or H7 virus can't adapt well enough to start a pandemic, only that we've never seen it happen (yet).