Wednesday, June 16, 2021

V. Evolution: Genomic Evolution, Transmission Dynamics, and Pathogenicity of Avian H5N8 Viruses Emerging in China, 2020


Although the pandemic has garnered the bulk of our attention, we've also been keeping a close eye on the gradual return and spread of Avian H5 viruses (primarily H5N8) following a 3-year hiatus across much of the globe.  

While once - along with H7N9 - atop our pandemic worry list, both subtypes went to ground following China's massive poultry vaccination campaign of 2017. 

Some pockets of HPAI H5 remained, of course, and we saw scattered reports from Russia, Eastern Europe, and the Middle East in 2018-2019, but nothing on the scale that we'd seen prior to 2017. And reports of human infections with H5N1, H7N9 and H5N6 all but disappeared. 

While China's H7N9 remains greatly suppressed, since early in 2020 we've seen a resurgence of HPAI H5 - in particular HPAI H5N8 - both in Europe and Asia.  While related to the subtype that sparked the 2016 European epizootic (clade, these new incursions were described as `genetically distinct' from past incarnations we'd seen. 

Pre-Print: Novel Incursion of a HPAI H5N8 Virus in the Netherlands, October 2020

Influenza virus evolution is driven primarily by antigenic drift (replication errors), and antigenic shift (reassortment).  Generally, reassortment (see below) causes the most dramatic changes. 

A reassortment of a far more benign H5N8 virus in either China or Russia over the summer of 2016 led to Europe's largest avian epizootic on record (see EID Journal: Reassorted HPAI H5N8 Clade - Germany 2016).

Other reassortment events, often in China, have led to further expansion of HPAI H5 viruses, including the infamous 2005 bird die off at Qinghai Lake, China signaling the emergence of clade 2.2 (aka QH05) of the H5N1 virus, when then quickly moved into Europe and the Middle East.

Over the past year we've seen a number of suspicious bird die offs, both in Russia and in China, which often indicate the emergence of a new, more virulent (at least in birds), avian flu subtype. Over the summer of 2020, Russia reported die offs of wild birds, and outbreaks in poultry, due to HPAI H5N8.

Followed last fall by Europe's second largest avian epizootic on record, with - you guessed it - a `genetically distinct' H5N8 virus.

Since then we've seen several H5N8 related wild bird die offs in China (see here here, and here)  - and most notably - in February of 2021, Russia reported the first confirmed human infections with avian H5N8 (see Russian Media Reports 7 Human Infections With Avian H5N8).

While how much of a threat avain H5N8 will pose in the future is unknown, in May the CDC Added Zoonotic Avian A/H5N8 To Their IRAT Listwhile last March the WHO called for the creation of a Candidate Vaccine Virus (CVV) for this new H5N8 virus (see WHO: Candidate Vaccine Viruses for Pandemic Preparedness - March 2021). 

In May, in Science: Emerging H5N8 Avian Influenza Viruses, we looked at a cautionary report by two well respected Chinese scientists who warn on the zoonotic potential of H5N8. 


Emerging H5N8 avian influenza viruses
Weifeng Shi1,2,
George F. Gao3,4

Today we've another look at the quiet evolution of HPAI H5N8 in China, this time published in Virus Evolution, that describes the rapid rise last summer of an antigenically distinct H5N8 virus that is lethal to chickens and mice, that is similar to the Russian Zoonotic strain, and shows signs of mammalian adaptation.

Genomic evolution, transmission dynamics, and pathogenicity of avian influenza A (H5N8) viruses emerging in China, 2020
Jiahao Zhang, Xudong Li, Xiaomin Wang, Hejia Ye, Bo Li, Yiqun Chen, Junhong Chen, Tao Zhang, Ziwen Qiu, Huanan Li ... Show more
Virus Evolution, Volume 7, Issue 1, January 2021, veab046,
06 May 2021


Multiple recent outbreaks of highly pathogenic H5N8 viruses originating in aquatic birds frequently occurred in most European countries, Russia, South Korea, and Japan during the winter of 2020–21, and one zoonotic event of poultry workers infected with novel H5N8 viruses were reported in Russia. 

Strikingly, these novel H5N8 viruses had emerged and been co-circulating in wild birds and poultry in multiple provinces of China during 2020–21. In China, the population of aquatic birds has risen significantly in the past twenty years, and China is regarded as the largest reservoir for influenza viruses carried in aquatic birds across the globe. Hence, the co-circulation of these novel H5N8 viruses poses an alarming threat to not only poultry industry but also human health

In this study, we sequenced full-length genomes of these H5N8 viruses circulating in China. Phylogenetic analysis demonstrated that poultry-origin H5N8 viruses in China fell within wild birds-origin clade H5N8 viruses from Europe during 2020–21, and notably, were genetically closely related to human-infecting H5N8 viruses in Russia. Moreover, they possessed several molecular markers associated with mammalian adaption. 

Bayesian coalescent analysis showed that these H5N8 viruses might have introduced into China during June–September 2020, suggesting that these H5N8 viruses might have introduced via wild bird migration or poultry trade. Besides, we also found that the effective population size of clade H5N8 viruses dramatically increased during the winter season of 2020/21, as is consistent with previous increase of genetic diversity during the winter seasons of 2013/14 and 2016/17, which indicated that the wild bird migration accelerates the genetic diversity of these H5N8 viruses during the winter season of 2020/21. 

Notably, these novel H5N8 viruses were lethal to chickens and mice, highly transmissible to ducks, and were antigenically distinct from H5 viruses circulating in China, posing considerable threats to public health. Our findings offer novel insights into the evolution and risk assessment of H5N8 viruses during the winter season of 2020–21.

          (Continue . . . )

In addition to H5N8, we've also seen an uptick in human H5N6 infections in China, the first known Human Avian H10N3 Infection In Chinaan as-yet unconfirmed report of human H5N1 infections in Nigeria (see The ECDC On The Recent Nigeria H5N1 Report Of Suspected Human Infections), and a recent surge in H5 avian flu activity in the Middle East. 

Since it is summer in the Northern Hemisphere, avian flu activity is currently somewhat restricted, but come the fall tens of millions of birds will leave their high-latitude roosting sites and head south for the winter. 

We can't predict what kind of avian flu season they are going to bring, but we can see that avian flu activity is ramping up globally, and is evolving in worrisome directions.  While we've still got our hands full dealing with the coronavirus pandemic, we ignore other potential zoonotic threats at our own peril.