Host-pathogen evolutionary signatures reveal dynamics and future invasions of vampire bat rabies

Abstract

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

Keywords: Desmodus; forecasting; sex bias; spatial dynamics; zoonotic disease.

Fig. 1.

Genetic and geographic structure of host and viral markers with distinct inheritance mechanisms. (A) The ML tree of VBRV, using 434 complete N sequences from Peru (colored branches) and other representative countries in the Americas (black branches; ARG, Argentina; BRA, Brazil; COL, Colombia; ESA, El Salvador; GUY, French Guiana; MEX, Mexico; TRI, Trinidad; URU, Uruguay). Colored symbols show bootstrap support from 1,000 replicate ML searches. Two outgroup sequences from a rabies variant circulating in Peruvian dogs were excluded for visualization. (B) Geographic distributions of viral lineages in Peru. Areas above 3,600 m (the upper limit to vampire bats in Peru) are colored gold. (C) Bayesian phylogenetic tree of cytB sequences from vampire bats from Peru (n = 442) and other countries in the Americas (n = 26). Branches are colored by geographic region. Node values are posterior probabilities. (D) Distribution of CytB haplotypes across vampire bat colonies in Peru. Sites with <8 sequenced individuals were grouped with other colonies surveyed within 10 km. Pie charts are proportionate to sample size (range = 8–30). (E) Estimates from STRUCTURE analyses assuming K = 2–6 populations using 9 microsatellites (n = 480 bats). Each bar represents the probability of membership assignment to each of K groups. (F) Pie charts show the distribution of microsatellite groups [K = 3, threshold probability for group membership = 0.85, unassigned individuals (U) in white].

Fig. 2.

Dynamics of historical viral dispersal within Peru. Bayesian phylogenetic trees of VBRV L1 (A) and L3 (B), with tip symbols colored according to department of Peru (C). Inner node symbols are PPs of clades. (D) Spatial expansions of each viral lineage, depicted as the cumulative geographic distance from the inferred outbreak origin through time. (E) Posterior distributions of the epidemic velocity and diffusion coefficient of each viral lineage. Points are parameter estimates from the tips of one randomly sampled tree from the posterior distribution of each Bayesian phylogeographic analysis. Solid diamonds and lines are the median and 95% HPDs on parameter estimates, respectively. Black diamonds are median statistics calculated across all branches. Vertical dashed lines are the 95% bounds of the wavefront velocity estimated from time series data in northern Peru (Fig. 3 and SI Appendix, Fig. S9).

Fig. 3.

Forecasting invasion of VBRV to the Pacific coast of South America. (A) The South American range of vampire bats, colored as in Fig. 1. Red lines are least-cost pathways from bat colonies in the Andes and Amazon with MG3 individuals (typical of the coast) to Lima using the “valley” resistance model. The black box indicates the region in B. (B) Blue lines are least-cost routes from the westernmost VBRV outbreak in 2012 (green point) to Chiclayo (a reference point for the Pacific coast) according to the valley (solid) and threshold (dotted) resistance models. Red lines are routes from the western front of the epidemic in 2015. Light blue points (2004–2012) are outbreaks that were included in phylogenetic analyses.