#17,040
When we talk about avian flu viruses with zoonotic (or even pandemic) potential, the various incarnations of H5N1 first come to mind, followed perhaps by China's H7N9 virus. Between them they have caused thousands of infections and hundreds of deaths during the 21st century, but reports of both have declined sharply in recent years.
H5N6, also from China, continues to worry researchers, with 80 cases reported on the Mainland since 2014 (see map below) and a high fatality rate (40%-50%).
LPAI H9N2 has caused roughly 100 known infections (and undoubtedly many more undiagnosed), primarily is Asia, but generally produces mild to moderate illness. To that we can add sporadic human infections by H10Nx and H7N4 viruses in China, H7N2 (infecting cats and humans in NYC), and this year, China reported the first two known infections by avian H3N8 (see IJID: A Review Of The Pandemic Potential Of Avian H3N8).
There are a lot of novel avian flu viruses with zoonotic potential (that, along with swine variant viruses), could spark the next global health crisis.
Including H6 viruses, which don't get a lot of attention, but are common in both wild birds globally and in domesticated poultry in China, and have demonstrated the ability to jump species (to humans, to pigs, and to dogs) as well. Some past blogs include:
- In 2013, LPAI H6N1 was identified as the cause of pneumonia in a human in Taiwan. The patient, a 20-year-old female, was hospitalized with mild pneumonia on May 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on May 11th.
- The following year, we learned that H6N1 had jumped to Taiwanese dogs (see Taiwan: Debating The Importance Of H6N1 In Dogs).
- In 2015's EID Journal: Seropositivity For H6 Influenza Viruses In China, researchers found a a small, but significant number of people in their survey who tested positive for H6 influenza antibodies (indicating previous exposure).
- Also in 2015, in Study: Adaptation Of H6N1 From Avian To Human Receptor-Binding, we saw a report citing changes the authors suggest are slowly moving the H6N1 virus towards preferential binding to human receptor cells instead of avian receptor cells
- LPAI H6N6 emerged in Chinese swine more than a decade ago (see Pathogenicity and transmission of a swine influenza A(H6N6) virus), and continues to show signs of adaptation to mammalian hosts (see Trans. Emerg, Dis: Continued Reassortment of Avian H6 viruses - Southern China, 2014-2016.)
Two years ago, in Nature: Evolution & Pathogenicity of H6 Avian Influenza Viruses, Southern China 2011-2017, we looked at study on the evolution of H6 viruses in China, and their growing adaptation to mammalian physiology.
Today we have another study published in the Journal of Virus Eradication, which warns that H6N6 viruses continue to evolve, and are becoming better adapted to human physiology, and that their threat to human health may be increasing.
This is a lengthy, and quite detailed, open-access report and I've only posted some highlights. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Influenza A (H6N6) viruses isolated from chickens replicate in mice and human lungs without prior adaptation
Weijuan Zhong Lingxi Gao Xijing Wang Shanggui Su Yugui Lin Kai Huang Siyu Zhou Xiaohui Fan Zengfeng Zhang
https://doi.org/10.1016/j.jve.2022.100086
AbstractThe H6H6 subtype avian influenza virus (AIV) is currently prevalent in wild birds and poultry. Its host range has gradually expanded to mammals, such as swines. Some strains have even acquired the ability to bind to human-like SAα-2,6 Gal receptors, thus increasing the risk of animal to human transmission. To investigate whether the H6N6 AIV can overcome interspecies barriers from poultry to mammals and even to humans, we have assessed the molecular characteristics, receptor-binding preference, replication in mice and human lungs of three chicken-originated H6N6 strains.
Among these, the A/CK/Zhangzhou/346/2014 (ZZ346) virus with the P186T, H156R, and S263G mutations of the hemagglutinin molecule showed the ability to bind to avian-like SAα-2,3 Gal and human-like SAα-2,6 Gal receptors. Moreover, H6N6 viruses, especially the ZZ346 strain, could replicate and infect mice and human lungs. Our study showed the H6N6 virus binding to both avian-like and human-like receptors, confirming its ability to cross the species barrier to infect mice and human lungs without prior adaptation. This study emphasizes the importance of continuous and intense monitoring of the H6N6 evolution in terrestrial birds.
(SNIP)
Discussion
The H6N6 subtype AIV is widely prevalent in poultry, and its host range has expanded to mammals. Undoubtedly, it has become an endemic disease of domestic fowl and animals. Here, three chicken-originated H6N6 subtypes of AIV were of multiple reassortment viruses, with gene segments derived from the Gr(SNIP)oup-II (ST2853-like) of Eurasian lineages. Terrestrial birds may be an intermediate host in the cross-species transmission of the influenza virus from birds to humans.35,36 At the same time, molecular epidemiological investigations have shown that the H6N6 subtype AIV is prevalent in terrestrial chickens.14 Therefore, the H6H6 virus in chickens may acquire the potential to infect humans.
The switch of the receptor-binding preference from the avian-like SAα-2,3 Gal to the human-like SAα-2,6 Gal receptor is a key factor in AIV crossing interspecies barriers and efficiently transmitting to humans. The receptor-binding domains in the head of the influenza virus HA can specifically recognize and bind to the avian-like SAα-2,3 Gal and/or human-like SAα-2,6 Gal receptors; yet, the molecular mechanism of receptor-binding preference switch in different avian influenza virus subtypes needs to be further elucidated. The H5N1 HA with the N224K/Q226L mutations has a key role in switching the receptor-binding preference from the avian-like SAα-2,3 Gal to the human-like SAα-2,6 Gal receptor.37 The HA with the Q226L and G186V mutations in the H7N9 virus could result in virus binding to the human-like receptors, and the H6N6 HA with the S137 N, E190V, and G228S mutations is essential in the process of acquiring the ability to recognize human-like virus receptors.38, 39, 40
(SNIP)
The first case of human infection with the H6N1 avian influenza virus was reported on May 20, 2013, in Taiwan.5 The emergence of human cases infected with H6N1 shows the unpredictability of influenza virus transmission and the potential threat from novel viruses. Some studies have reported that the influenza virus responsible for a pandemic is generated by avian-human (or-swine) influenza A virus reassortments,43 but the AIV involved in the reassortment is not necessarily a highly pathogenic one. Moreover, mild symptoms caused by low pathogenic viruses can be easily overlooked, increasing the chances of virus spread, adaptive mutation, and reassortment. Currently, prevention and control of the influenza pandemic are mainly focusing on the H5N1 and H7N9 subtypes which cause severe human disease and deaths. However, due to the unpredictability and gaps in knowledge about influenza, we cannot predict which subtype of the influenza A virus will cause the next pandemic.Although the H6N6 virus has low pathogenicity, it is widely prevalent in poultry. It has repeatedly infected swines, with the potential to evolve into a novel influenza virus infecting human beings. Therefore, this study has confirmed that some chicken-originated H6N6 viruses might acquire the ability to recognize and bind to human-like receptors, thus increasing risk to humans. Our study emphasizes the importance of continuous and intensive monitoring of these viruses evolution to prevent transmission to humans.
While avian H6 viruses don't get a lot of press, and aren't represented on the CDC's IRAT (Influenza Risk Assessment Tool) list of novel flu viruses with pandemic potential - they continue to reassort, evolve, and spillover into non-avian species - making them very much worthy of our attention.
