Global genetic variation and transmission dynamics of H9N2 avian influenza virus

Abstract

The H9N2 influenza viruses are extensively circulating in the poultry population, and variable genotypes can be generated through mutation, recombination and reassortment, which may be better adapted to infect a new host, resist drug treatment or escape immune pressure. The LPAI H9N2 viruses have the potential to evolve towards high levels of virulence in human. Some studies about the regional dispersal were reported, but global dissemination and the drivers of the virus are poorly understood, particularly at the genome scale. Here, we have analysed all eight gene segments of 168 H9N2 genomes sampled randomly aiming to provide a panoramic framework for better understanding the genesis and genetic variation of the viruses, and utilized phylogeography and spatial epidemiology approaches to uncover the effects of the genetic variation, predictors and spread of H9N2 viruses. We found that more frequent reassortment events involve segments PA, NP and NS, and 21 isolates have possible mosaic structure resulting from recombination events. Estimates of gene-specific global dN/dS ratios showed that all genes were subject to purifying selection. However, a total of 13 sites were detected under positive selection by at least two of three methods, which located within segments HA, NA, M2, NS1 and PA. Additionally, we inferred that NA segment has the highest rate of nucleotide substitution, and its tMRCA estimate is the youngest than the remaining segments' inference. About the spatial history, air transportation of human was identified as the predominant driver of global viral migration using GLM analysis, and economic factors and geographical distance were the modest predictors. Higher migration rates were estimated between five pairs of regions (>0.01) indicating the frequent migration of the viruses between discrete geographical locations. Further, our Markov jumps analysis showed that viral migration is more frequent between Southern China and Northern China, and high rate of gene flow was observed between America and East Asia. Moreover, the America together with Southeast Asia acted as the primary hubs of global transmission, forming the trunk of evolutionary tree. These findings suggested a complex interaction between virus evolution, epidemiology and human behaviour.

Phylogeographic Dynamics of Influenza A(H9N2) Virus Crossing Egypt

“…Previous studies have shown extensive expansions to the Middle East after its first emergence in Asia, forming a close genetic linkage between two regions (Fusaro et al, 2011;Nagy et al, 2017;Wei and Li, 2018). Furthermore, phylogenetic divergence of Asian and the Middle Eastern H9N2 viruses has also been reported through the ongoing viral evolution (Fusaro et al, 2011;Hu et al, 2017;Naguib et al, 2017;Wei and Li, 2018). Together, these finding indicated that Asia served as the original transmission source of global H9N2 viruses, but our analyses give heighten the distinct role of Middle East as transmission hub in shaping the following spatial expansions.…”

“…However, although we have subsampled all of the available H9N2 HA genetic diversity, it is important to note that reporting LPAIVs H9N2 varies between different countries our analysis is just reflecting the currently available data. Previous studies have shown extensive expansions to the Middle East after its first emergence in Asia, forming a close genetic linkage between two regions (Fusaro et al, 2011;Nagy et al, 2017;Wei and Li, 2018). Furthermore, phylogenetic divergence of Asian and the Middle Eastern H9N2 viruses has also been reported through the ongoing viral evolution (Fusaro et al, 2011;Hu et al, 2017;Naguib et al, 2017;Wei and Li, 2018).…”

Host diversity and behavior determine patterns of interspecies transmission and geographic diffusion of avian Influenza A subtypes among North American wild reservoir species

“…This allows the simultaneous inference of viral transition rates among specified traits (i.e., hosts or locations) and their association with covariates that may drive viral movement. This approach has been adapted to investigate the role of anthropogenic and environmental variables on the diffusion of avian influenza within China (17) as well as of avian influenza subtype H9N2 on a global scale (18). The GLM has also been used to uncover the impact of host behavior on the dispersal of rabies virus among bat species (19).…”

Live bird markets as evolutionary epicentres of H9N2 low pathogenicity avian influenza viruses in Korea

“…H9N2 has become the most prevalent subtype of low pathogenic avian influenza in poultry. After introduction to Eurasian poultry, this virus has diverged into five genetic lineages: G1, Y280, BJ94, G9, and Y439/Korea lineage [2] and has become endemic in poultry across Asia, the Middle East, and North Africa [3].…”