Bayesian Phylodynamic Analyses of Segment 10 Reveals Global Origin, Spread, and Host Transmission of Bluetongue Virus

• ¹ Kuwait University, Faculty of Public Health, Kuwait
• ² VISAVET Health Surveillance Centre (UCM), Spain
• ³ Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, United States

Bluetongue virus (BTV) is a midge-borne disease that causes notable morbidity and mortality in non-African ungulates, especially sheep [1]. BTV epidemics are economically constraining and have caused global losses of up to US$ 3 billion [2]. Understanding the global evolutionary epidemiology of BTV is critical in designing intervention programs. Bayesian phylodynamic methods can uniquely integrate spatiotemporal and host characteristics metadata into the phylogeny using one statistical framework. Very few studies have attempted to reconstruct the evolutionary history of BTV on either local or regional scales [3-5]. However, and to the authors’ knowledge, no attempt has yet been made to identify BTV geographic origins and transmission dynamics on a global scale using discrete phylodynamic models. The objective of the study was to explore evolutionary characteristics, spatiotemporal origins, and host transmission dynamics of BTV on a global scale using all publicly available segment 10 sequences collected between 1937 and 2016 (N = 560). We used Bayesian discrete phylogeographic models to reconstruct the spatiotemporal origin and dispersal of BTV between 15 affected countries. Similarly, we used discrete-trait phylodynamic models to identify the ancestral host species for BTV and quantify the transmission routes of the virus between sheep, goat, cattle, and midges. The inferred posterior estimate of the mean nucleotide substitution rate was equal to 3.11 × 10-4 /site/year with a 95% highest posterior density (HPD) ranging from 2.05 × 10-4 to 4.66 × 10-4. The approximate divergence time of the virus was inferred to be over 1000 years ago in Asia and Europe. However, BTVs isolated in Australia emerged in the 1700s and were inferred to be the youngest among viruses isolated from other continents. The relative genetic diversity through time for BTV have substantially increased during the 1930s, followed by a drastic decline in the 1970s. The relative genetic of the BTV through time has substantially increased during the 1930s, followed by a drastic decline in the 1970s. However, a slight sign of an increase in the genetic diversity is noted for BTVs isolated in 2016. The root state posterior probabilities inferred from our phylogeographic analyses suggested China as the ancestral location for BTV (P = 0.11), where novel serotypes are continuously emerging [6-8]. The phylogeographic maximum clade credibility (MCC) tree indicated the transcontinental spread of BTV was established in the 1500s between China, South Africa, and the USA. However, most statistically significant dispersal routes (Bayes factors > 2000) of the virus were inferred between European countries where the majority of BTV outbreaks are observed [9]. Furthermore, the highest intensity of viral jumps was inferred for France and Italy. Results suggested that goats are the ancestral host of BTV (P = 0.34) over 1000 years ago, whereas the majority of later transmission events originated from sheep. However, substantially significant transmission routes (BF > 10000) were inferred from and to cattle, confirming the notion that cattle are important reservoirs for BTV spread and maintenance [10]. Finally, the highest mean counts of viral jumps were inferred between sheep and midges, highlighting the intensity of the transmission cycle between the two hosts [9]. Findings from the present study shed novel insights into the global spatiotemporal evolutionary history of BTV and highlighted important aspects of the transmission dynamics of the virus between host species using a well-established and rigorous analytical framework. While the results may be sensitive to the inherent limitations of imperfect BTV molecular surveillance, our analysis elucidates important epidemiological aspects of BTV origin and spread on global scales. Subsequently, the mobilization of further resources toward molecular surveillance of BTV is justified, which is key to guiding disease control and prevention worldwide.