Highly Pathogenic Avian Influenza and its Complex Patterns of Reassortment

Abstract

Highly Pathogenic Avian Influenza H5NX (clade 2.3.4.4b) is responsible for major outbreaks in poultry and wild birds in recent years.  In 2014/2015, 2016/2017 and 2020/2021 the main subtype in Europe was H5N8, however for 2021/2022 and 2022/2023 seasons, the virus acquired a different neuraminidase making subtype H5N1.  It has also undergone additional reassortments with internal protein coding segments from other low pathogenic strains and spread intercontinentally to the Americas, Africa and Asia.

Using a sequence dataset of over 4000 genomes, we propose a method for determining and classifying reassortants suitable for further phylogenetic analysis.  For each segment, the genetic distance between pairs of sequences is calculated, and sequences are grouped into 1.5-2% similarity clusters, and labelled according to size.  The reassortment code of a whole-genome is composed of the individual segment cluster labels.  With this method we see that there are 2-3 main reassortants in Europe for 2021-2023, particularly with different polymerase segments.  The donor viruses for these reassorted segments largely originate from other co-circulating ‘Eurasian-pool’ low pathogenic strains, however one reassortant which has been severely affecting gulls and other seabirds also has segments from a ‘Northern-pool’ of viruses (Alaska and Northern Europe).  Additionally, once in the Americas, there are multiple reassortments with co-circulating low pathogenic America’s lineages.

Next, reassortants fitness properties in the population were estimated from phylodynamic growth rates of viral effective population size from time-scaled phylogenies as a function of genome composition, and bird-species with BEAST2 Birth-Death-Multitype-Models.  We also used local branching index to provide a relative lineage growth measure with different bird-species at each node in the tree.  Coupled with dates and spatial locations inference of the ancestral nodes, we are able to map the spatial and host species origin, dissemination, and initial fitness of the different reassortants.

We find that the H5N1 strain has mixed with previously co-circulating low pathogenic viruses and acquired polymerases and other internal protein coding segments, resulting in fitter viruses in certain avian populations and further spread.  We predict the reassortants will continue in the autumn in Europe, and expect further reassortments in the Americas.

Note: This conference abstract was presented at the 9th International Conference on Infectious Disease Dynamics organized by the journal Epidemics. This abstract has not been screened by SSRN for potential for public harm and should not be used to inform any clinical decision making. No competing interests or funding statements have been declared.