Quasispecies dynamics in arbovirus persistence emergence and fitness
Predicting genetic determinants of Zika virus emergence
The explosive epidemics of West Nile and Zika viruses were in part driven by virus adaptation to local mosquitoes. This new project seeks to determine whether Zika virus may similarly adapt to local mosquitoes. It also aims to define how environmental temperatures shape virus infections during incubation in mosquitoes. This project is sponsored by NIH.
Pictured: Uninfected Aedes aegypti mosquito taking in blood meal. Photo by John Eisele.
Emergence of tick borne encephalitis in North America
Tick-borne encephalitis cases attributed to Powassan virus are now being increasingly reported from New England and the upper Midwest. We seek to better understand why this flavivirus has emerged and whether risk will continue to increase. The successful completion of this project may help drive efforts to environmentally manage deer ticks, which also transmit Lyme disease. Ultimately, by better understanding Powassan genetic diversity, we can better define the potential for tick borne encephalitis to further emerge as a public health burden in North America.
Role of cell tropism for Zika virus pathogenesis and transmission
This project seeks to define how specific cell types contribute to Zika virus pathogenesis and transmission. We are using a ZIKV infectious clone developed in our laboratory that has been modified with cell-type specific miRNA target sequences that specifically silence replication in a given type of cell. This project is sponsored by NIH and is a collaborative effort between our lab and that of Aaron Brault at CDC.
Pictured: Finished plaque assay, used for determining viral titer. Photo by John Eisele.
Engineering Therapies that Evolve to Autonomously Control Epidemics
The aim of this project is to engineer flavivirus defective interfering particles (DIPs), viral genomes which are unable to replicate themselves due to lack of essential protein coding regions. DIPs can, however, compete with wild-type viruses by utilizing the proteins produced during normal replication to propagate themselves, which limits the resources available to the infectious virus. In this way, DIPs have potential as novel antiviral agents.
Investigating the Evolutionary Drivers of Codon Usage in Viral Genomes That Infect Both Arthropods and Vertebrates
Codon usage varies between viruses that infect different host species. Viruses that infect both arthropods and vertebrates evolve genomes that have to balance between the differential pressures of these two host systems. We are working to understand the specific pressures that drive differential codon usage between viruses that infect single hosts versus multiple hosts.
Pictured: RNA codon chart, a reference that identifies the nucleotide combinations that code for various amino acids. Image courtesy of Wikimedia Commons.
Xenosurveillance: a novel approach for interrogating the human – pathogen landscape in sub-Saharan Africa
The goal of this study is to define whether mosquitoes collected from huts in rural Africa can be used for biosurveillance. The central concept that drives this proposal is the idea that mosquitoes frequently sample human blood and that this blood contains information on the health of that person. In particular we are evaluating the sensitivity of conventional and next-generation methods for detecting pathogen signatures in the blood of mosquitoes (including non-arthropod-borne agents). We are also attempting to correlate mosquito-derived data to clinical disease. This project has been funded by CSU and by the US Department of Defense. It is a large and highly collaborative project involving: Brian Foy (epidemiology, field biology and medical entomology, AIDL, Colorado State University); Mark Stenglein (computational biology, Colorado State University); Fatorma Bolay (field studies, Liberian Institute for Biomedical Research); Joseph Diclaro (medical entomology, field studies, NAMRU-3).
Analysis of Zika virus emergence and functional evolution in the Americas
The unexpected scale and severity of the 2015-16 Zika virus epidemic led several scientists to hypothesize that recent evolutionary events in the virus were to blame. The relative lack of Zika virus genetic data, however, has hindered efforts to test key evolutionary hypotheses of Zika virus emergence. As part of a collaboration with the Scripps Research Institute and Yale University, we have helped developed methods to successfully sequence Zika virus directly from clinical and mosquito samples, leading to a major expansion of available genomic data of the virus.
Pictured: Zika virus capsid. Image courtesy of Wikimedia Commons.
We also frequently partner with industry to help translate basic science findings to the field, and to develop new tools to fight arthropod-borne and emerging diseases. For example, some of our previous partnerships involved the testing of a novel tick and flea trap, as well as vector-competence testing for a live-attenuated dengue virus vaccine candidate. Contact Greg for further information.
West Nile virus surveillance
We conduct surveillance testing for Ft. Collins, Loveland, and Berthoud, CO. In addition to providing important data to the public, this project serves as an important training opportunity for students and fellows and provides us with potentially useful WNV strains from Colorado. Trap data reports, risk maps, and weekly vector indices are updated weekly and are available online through the City of Fort Collins website.
Pictured: 2018 Fort Collins mosquito surveillance map, courtesy of Vector Disease Control International.