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. 2012 Nov 27;109(48):19715-20.
doi: 10.1073/pnas.1203456109. Epub 2012 Nov 12.

Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats

Daniel G Streicker  1 , Sonia M Altizer, Andrés Velasco-Villa, Charles E Rupprecht
Affiliations

Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats

Daniel G Streicker et al. Proc Natl Acad Sci U S A. .

Abstract

Determining the genetic pathways that viruses traverse to establish in new host species is crucial to predict the outcome of cross-species transmission but poorly understood for most host-virus systems. Using sequences encoding 78% of the rabies virus genome, we explored the extent, repeatability and dynamic outcome of evolution associated with multiple host shifts among New World bats. Episodic bursts of positive selection were detected in several viral proteins, including regions associated with host cell interaction and viral replication. Host shifts involved unique sets of substitutions, and few sites exhibited repeated evolution across adaptation to many bat species, suggesting diverse genetic determinants over host range. Combining these results with genetic reconstructions of the demographic histories of individual viral lineages revealed that although rabies viruses shared consistent three-stage processes of emergence in each new bat species, host shifts involving greater numbers of positively selected substitutions had longer delays between cross-species transmission and enzootic viral establishment. Our results point to multiple evolutionary routes to host establishment in a zoonotic RNA virus that may influence the speed of viral emergence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Episodic positive selection in the bat RV phylogeny. Maximum likelihood topologies of the bat RV N, G and L genes are shown in A, B and C, respectively. Symbols indicate amino acid changes in putatively positively selected sites only. Color spectra of points follow the relative position along each gene. Inset pie charts show the ratio of internal to tip substitutions for all sites in each gene. Lineage labels denote the reservoir host species as follows: Ap, Antrozous pallidus; Ct, Corynorhinus townsendii; Dr, Desmodus rotundus; Ef, Eptesicus fuscus; Efr, Eptesicus furinalis; Hm, Histiotus montanus; Ln, Lasionycteris noctivagans; Lb, Lasiurus borealis; Lc, Lasiurus cinereus; Le, Lasiurus ega; Li, Lasiurus intermedius; Ls, Lasiurus seminolus; Lx, Lasiurus xanthinus; Mm, Molossus molossus; M, Myotis sp.; Ma, Myotis austroriparius; Mc, Myotis californicus; Mn, Myotis nigricans; My, Myotis yumanensis; Nh, Nycticeius humeralis; Nl, Nyctinomops laticaudatus; Ph, Parastrellus hesperus; Ps, Perimyotis subflavus; Tb, Tadarida brasiliensis.
Fig. 2.
Fig. 2.
Demographic histories and transition times to epizootic growth for 11 bat RV lineages. Each graph shows a Bayesian skyline plot estimated from N gene data. The effective number of infections is the product of the effective population size (Ne) and the generation time between infections (τ). Dashed lines are the 95% highest posterior density. Overlaid histograms show the posterior distributions of the transition times between historical (pregrowth) and contemporary demographic periods from the two-epoch models, with 95% limits shaded in red. Small black triangles are median transition times. The vertical axis for histograms was varied across graphs to enable comparable visualization, and the scale was therefore omitted. Top Right graph shows a schematic for calculating the epizootic lag time from the two-epoch models and the joint phylogeny. The epizootic lag time for virus A is T0 – T2, when including inferred ancestral-host states (scenario 2); or T1 – T2, when the origins of host shifts were treated as unknown (scenario 1).
Fig. 3.
Fig. 3.
Relationship between the number of positively selected amino acid changes in G and L and the epizootic lag time. Substitutions on terminal branches and in N were excluded because the timing of these substitutions was inconsistent with a postulated role in host adaptation. The black line and points show the median relationship with corresponding statistics in the Upper Left corner. Gray lines show 2,000 model predictions using random draws from the posterior distribution of epizootic lag time for each viral lineage. The inset histogram shows the distribution of the slope parameter from the iterated models, with 95% limits shaded in black (note the lack of overlap with zero).
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