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Although it is far from certain where and when HPAI H5N8 will show up this winter, after last year's record epizootic in Europe and its unusual persistence over the summer, few would bet that we've seen the last of this emerging virus.
From its arrival last November it was apparent that the H5N8 virus had changed markedly in the 18 months since its last appearance in Europe, spreading faster and causing greater mortality in wild birds and poultry than we've seen before (see Europe: Unusual Mortality Among WIld Birds From H5N8).In early January we learned H5N8 had reassorted - likely over the previous summer somewhere in Russia or Mongolia - producing new, more virulent virus (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016).
About the same time, we were also starting to see spin offs of new subtypes (see HPAI H5N5 Detected In German Poultry Operation).
HPAI H5N8 was proving itself to be not only more virulent than its predecessor, it was displaying a remarkable ability to continually reinvent itself (through reassortment) as it spread across Europe, Africa, and the Middle East. The FLI: Updated Risk Assessment On HPAI H5 repeatedly warned over the winter and spring that:
`Generation of reassortants always must be expected when different high and low pathogenic influenza viruses are circulating in one population.'While we wait to see what arrives this winter, we've a new research report in the EID Journal that describes the rapid generation of new reassortants among H5N8 viruses in the Netherlands last winter, and warns that additional changes could alter the virus's behavior over time.
Volume 23, Number 12—December 2017
Research
Multiple Reassorted Viruses as Cause of Highly Pathogenic Avian Influenza A(H5N8) Virus Epidemic, the Netherlands, 2016
Nancy Beerens, Rene Heutink, Saskia A. Bergervoet, Frank Harders, Alex Bossers, and Guus Koch Author affiliations: Wageningen Bioveterinary Research, Lelystad, the Netherlands
Suggested citation for this article
Abstract
In 2016, an epidemic of highly pathogenic avian influenza A virus subtype H5N8 in the Netherlands caused mass deaths among wild birds, and several commercial poultry farms and captive bird holdings were affected.
We performed complete genome sequencing to study the relationship between the wild bird and poultry viruses. Phylogenetic analysis showed that the viruses are related to H5 clade 2.3.4.4 viruses detected in Russia in May 2016 but contained novel polymerase basic 2 and nucleoprotein gene segments and 2 different variants of the polymerase acidic segment.The saving grace with HPAI H5N8 has been its inability to infect humans. Over the past year, however, we've looked at a number of laboratory experiments showing that a few mutations in the right places might alter that equation.
Molecular dating suggests that the reassortment events most likely occurred in wild birds in Russia or Mongolia. Furthermore, 2 genetically distinct H5N5 reassortant viruses were detected in wild birds in the Netherlands.
Our study provides evidence for fast and continuing reassortment of H5 clade 2.3.4.4 viruses, which might lead to rapid changes in virus characteristics, such as pathogenicity, infectivity, transmission, and zoonotic potential.
(SNIP)
Discussion
The introduction of the HPAI H5N8 virus in the Netherlands in 2016 resulted in the death of many wild birds, and several commercial poultry and captive bird holdings were affected. We performed genetic analysis to study the relationship between wild bird and poultry viruses. Median-joining network analysis suggested that multiple separate introductions of the H5N8 virus occurred in the Netherlands.
This analysis also demonstrated that the viruses on 5 infected farms were not closely related (Figure 2). On the 3 farms in Biddinghuizen, highly similar viruses were identified, which might have resulted from either farm-to-farm spread or separate introductions from the same source. For most poultry farms, a dead wild bird infected with a related virus was found near the farm. We observed numerous genetic differences between the H5N8 viruses introduced in the Netherlands in 2016 versus 2014, indicating the 2016 epidemic was caused by a new introduction and not by continuous circulation of the 2014 virus.
Phylogenetic analysis showed that the H5N8 viruses introduced in the Netherlands in 2016 are novel reassortants of the Russia–Mongolia H5 clade 2.3.4.4 viruses. The virus obtained new PB2 and NP segments, and we detected 2 different PA segments in H5N8 viruses in the Netherlands. We found no correlation between PA segment and bird species between PA segment and geographic location (Technical Appendix 2 Figure 1 [cluster C]).
Molecular dating suggests that these reassortment events were completed in August 2016 and thus most likely occurred in wild birds in Russia-Mongolia. A recent genetic analysis of 2 wild bird and several poultry H5N8 viruses in Germany also identified the NP and PA reassortments (22). In addition, we identified PB2 as a reassortment on the basis of molecular dating studies and its similarity to PB2 in LPAI viruses. The PA II gene segment was not observed in H5N8 viruses in Germany or other countries in Europe, based on the analysis of sequences that are currently available. Furthermore, 2 genetically distinct H5N5 viruses have been found in the Netherlands. An analysis of the outbreak in Italy (23), published after submission of this manuscript, also showed multiple independent introductions of H5N8 and H5N5 viruses.
Those findings provide evidence for rapid and continuing reassortment of the H5 clade 2.3.4.4 viruses, which allow the virus to change its genetic architecture very quickly and might increase the ability of the virus to infect poultry or humans in the future. Hence, extensive surveillance of wild bird populations in the border area of Russia and Mongolia and in common breeding grounds in northern Siberia appears essential to enable early warning of novel reassortants and sequence mutations of H5 clade 2.3.4.4 viruses.
Dr. Beerens is a senior scientist and head of the National Reference Laboratory for Avian Influenza and Newcastle Disease in the Netherlands. Her research interests focus on molecular virology, genetics, and virus evolution.
Vet. Research: Synergistic AA Changes That Enhance Virulence Of H5N8 In Mice
J. Virulence : Altered Virulence Of (HPAI) H5N8 Reassortant Viruses In Mammalian ModelsWhile none of this ensures that HPAI H5N8 is going to evolve into a humanized pathogen - with the expected return of avian flu this fall and winter to Europe, Asia, and potentially North America - no one should take its previously benign nature for granted.
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions
