Many emerging viral pathogens are vertically transmitted in dipterans (dengue, West Nile, etc.). Understanding the genetic and evolutionary mechanisms that determine the virulence of vertically transmitted parasites is central to predicting and controlling these diseases. We will develop a model system combining theory with data for sigma virus, a vertically transmitted Rhabdovirus, in Drosophila melanogaster. The sigma virus-D. melanogaster system, with its ease of husbandry, extensive natural history, and wealth of genomic tools, is a superb model system for exploring 1) the evolution of virulence in general and 2) contrasting uniparentally vs. biparentally transmitted viruses in particular. Virulence, the damage done to the host, is a constantly evolving property in both established and emerging diseases;using an in vivo, animal model system to test the generality of results of virulence evolution from microbial or cell culture serial passage experiments is an essential initial step toward predicting and ultimately managing such evolutionary changes. Vertical transmission can maintain dangerous emerging viruses in their insect vector populations;information from a model system can help us predict and manage these viral reservoirs. We utilize a two-pronged experimental evolution study of sigma, an RNA virus, in intact animal hosts. First, we create replicated, artificial host shifts between D. melanogaster, in which infection is endemic;and in D. simulans, the host's sibling species, in which there is no infection. We thereby test predictions from microbial and cell culture serial passage experiments, which have not been evaluated before in an intact animal to the best of our knowledge. Specifically, we ask whether or not virulence necessarily increases with host shift;and whether or not """"""""shifted"""""""" virus is necessarily attenuated (less virulent) in the original host. Next, we manipulate viremia via artificial selection in D. melanogaster, contrasting outcomes under biparental vs. uniparental transmission, to test whether or not rates of evolution of virulence are dependent on precise mode of vertical transmission as predicted by some theory. In both projects, we also explicitly quantify the relationship between viremia, virulence, and male transmission. We also characterize genomic outcomes and the source and nature of adaptations resulting from experimental evolution via whole-genome sequencing. The theoretical components of the project use a variety of modeling tools ranging from simple genetic models to simulations to understand conditions governing the rate of the evolution of virulence. We provide both a general theory aim, incorporating elements from evolutionary ecology and population genetics;and a second aim connecting data from this project with existing theory on the evolution of virulence. Our experiments and theory will provide a generalized, integrated understanding of evolution of virulence;and represent a significant step forward in our understanding of viral evolution as relevant to human health by testing results from existing theory and from microbial and cell culture in an intact, animal system.

Public Health Relevance

This project aims to understand how vertically transmitted viruses (i.e., viruses transmitted from parents to offspring) become more or less harmful (i.e., change their virulence) and how they may change from one host to another. Data and models from this study will help scientists understand better how the virulence of human infectious diseases changes over time, how emerging diseases arise, and how we may be able to predict and control these changes;results will also help explain how insect-borne viruses such as West Nile and Dengue fever can persist in insect populations in the absence of human contact.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Florida
Schools of Arts and Sciences
United States
Zip Code
Piontkivska, Helen; Frederick, Madeline; Miyamoto, Michael M et al. (2017) RNA editing by the host ADAR system affects the molecular evolution of the Zika virus. Ecol Evol 7:4475-4485
Piontkivska, Helen; Matos, Luis F; Paul, Sinu et al. (2016) Role of Host-Driven Mutagenesis in Determining Genome Evolution of Sigma Virus (DMelSV; Rhabdoviridae) in Drosophila melanogaster. Genome Biol Evol 8:2952-2963
Smith, Val H; Holt, Robert D; Smith, Marilyn S et al. (2015) Resources, mortality, and disease ecology: Importance of positive feedbacks between host growth rate and pathogen dynamics. Isr J Ecol Evol 61:37-49
Graze, Rita M; McIntyre, Lauren M; Morse, Alison M et al. (2014) What the X has to do with it: differences in regulatory variability between the sexes in Drosophila simulans. Genome Biol Evol 6:818-29
Ascunce, Marina S; Fane, Jackie; Kassu, Gebreyes et al. (2013) Mitochondrial diversity in human head louse populations across the Americas. Am J Phys Anthropol 152:118-29
Rittschof, Clare C; Pattanaik, Swetapadma; Johnson, Laura et al. (2013) Sigma virus and male reproductive success in Drosophila melanogaster. Behav Ecol Sociobiol 67:529-540
Gandon, S; Hochberg, M E; Holt, R D et al. (2013) What limits the evolutionary emergence of pathogens? Philos Trans R Soc Lond B Biol Sci 368:20120086
Brusini, J; Wang, Y; Matos, L F et al. (2013) Virulence evolution in a host-parasite system in the absence of viral evolution. Evol Ecol Res 15:883-901
Barfield, Michael; Holt, Robert D; Gomulkiewicz, Richard (2011) Evolution in stage-structured populations. Am Nat 177:397-409
Wayne, Marta L; Blohm, Gabriela M; Brooks, Mollie E et al. (2011) The prevalence and persistence of sigma virus, a biparentally transmitted parasite of Drosophila melanogaster. Evol Ecol Res 13:323-345

Showing the most recent 10 out of 12 publications