Bayesian phylodynamics of avian influenza A virus H9N2 in Asia with time-dependent predictors of migration

Model-based phylodynamic approaches recently employed generalized linear models (GLMs) to uncover potential predictors of viral spread. Very recently some of these models have allowed both the predictors and their coefficients to be time-dependent. However, these studies mainly focused on predictors that are assumed to be constant through time. Here we inferred the phylodynamics of H9N2 viruses isolated in 12 Asian countries and regions under both discrete trait analysis (DTA) and structured coalescent (MASCOT) approaches. Using MASCOT we applied a new time-dependent GLM to uncover the underlying factors behind H9N2 spread. We curated a rich set of time-series predictors including annual international live poultry trade and national poultry production figures. This time-dependent phylodynamic prediction model was compared to commonly employed time-independent alternatives. Additionally the time-dependent MASCOT model allowed for the estimation of viral effective sub-population sizes and their changes through time and these effective population dynamics within each country were predicted by a GLM. International annual poultry trade is a strongly supported predictor of virus migration rates. There was also strong support for geographic proximity as a predictor of migration rate in all GLMs investigated. In time-dependent MASCOT models, national poultry production was also identified as a predictor of virus genetic diversity through time and this signal was obvious in mainland China and Bangladesh. Our application of a recently introduced time-dependent GLM predictors integrated rich time-series data in Bayesian phylodynamic prediction. We demonstrated the contribution of poultry trade and geographic proximity (potentially unheralded wild bird movements) to avian influenza spread in Asia. To gain a better understanding of the drivers of H9N2 spread, we suggest increased surveillance of the H9N2 virus in countries that are currently under-sampled as well as in wild bird populations in the most affected countries. Author summary What drives the geographic dispersal and genetic diversity of H9N2 avian influenza virus in Asia? We used two model-based approaches, DTA and MASCOT, to reconstruct the phylogeographic dynamics of the virus. Further, multiple potential predictors were used to inform the virus spread and population dynamics by GLMs. Here, we maximised the power of time-series predictors in Bayesian phylodynamic prediction. For the first time, we were able to quantify the contribution of both time-series and constant predictors to both migration rates and effective population sizes in a structured population. We identified a positive association of international poultry trade and national poultry production time-series with virus migration rates and effective population sizes respectively. We also identify geographic proximity as a strongly supported driver to virus migration rates and this points to the potential role of wild bird populations in virus dispersal across countries. Our study is a practical exemplar of the use of temporal information in predictors to model heterogeneous spatial diffusion and population dynamic processes and provides direction to H9N2 control efforts in Asia.