Incorporating evolutionary potential into zoonotic disease forecasts

Background/Question/Methods

Repeated viral spillover from wildlife to people has motivated studies on the biodiversity-human health connection. We now know that composition and diversity of host communities can influence viral prevalence, which can inform spillover forecasts. However, correlating viral prevalence to risk estimates does not account for potential pathogen evolution, which may significantly affect the likelihood that a spillover event occurs or that emergence results. One contribution to evolutionary lability is the amount of standing genetic variation within a population. Here we ask if the presence of an additional rodent host species increases the genetic diversity of three Lassa virus (LASV) genes within the primary host. We analyzed LASV sequences using two metrics of genetic diversity, population nucleotide diversity and pairwise genetic distance, to represent genetic diversity within and between sites, respectively. We then developed boosted classification trees that predicted the probability of presence for two host species and modeled the relationship between host diversity and LASV genetic diversity using generalized linear models and generalized dissimilarity models.

Results/Conclusions

The probability of presence of the secondary host was a significant positive predictor of genetic diversity within sites for both the glycoprotein and nucleoprotein genes of LASV. For the nucleoprotein gene, the interaction of both host species had a negative relationship with genetic diversity. Between sites, geographic distance was an expectedly significant, positive predictor of genetic distance for all genes. The difference in probability of presence of the secondary host was a positive predictor of genetic distance for the glycoprotein and nucleoprotein genes, but not so for the primary host. For the polymerase gene, no measure of host diversity significantly affected sequence diversity within or between sites. These results demonstrate that the genetic diversity of LASV within its primary host, from which most spillover into the human population originates, is affected by composition of the host community. By measuring genetic diversity, we consider evolutionary potential and find that additional hosts may increase zoonotic risk, even if the additional hosts are not responsible for transmission to humans. This work augments current ecological understanding of LASV dynamics, informing predictive models of zoonotic disease and their associated uncertainty in forecasting efforts.