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Principal Investigator: Gregory David Ebel
Organization: COLORADO STATE UNIVERSITY
Fiscal Year: 2024
Award: $335,392
Funding agency: National Institute of Allergy and Infectious Diseases
Arthropod-borne viruses (arboviruses) adapt to local conditions, maximizing their potential to perpetuate and
emerge as health threats. The adaptive potential of arboviruses is driven by error-prone replication, which
creates a genetically diverse pool of competing virus genotypes within each host. One of the most important
ways that the environment is changing is that temperatures are rising. This proposal examines some of the
ways that temperature may impact arbovirus evolutionary biology.
Aim 1 will address how a comprehensive temperature gradient that includes both constant and fluctuating
temperatures with varying means and amplitudes alters natural selection on WNV populations within
mosquitoes and the strength of bottlenecks. Our predictions are that fluctuating temperatures will increase the
strength of purifying selection, that diversity will be maximized at optimal constant temperatures, and that
bottlenecks will become wider as temperature increases. Flaviviruses infections are most frequently initiated by
aggregates of virus particles. Aim 2 will address the extent that this occurs in a host- and temperature-
dependent manner, bringing our previous work into a more ecologically relevant, realistic context. In the
second phase of Aim 2, we will ask whether these genome aggregates can help to facilitate the maintenance
of genetic diversity in the WNV population. This is important because population bottlenecks can significantly
impact virus fitness, and aggregation of genomes in individual infections may help viruses escape from them.
We have found that birds that generate high WNV viremia and are highly infectious to mosquitoes (crows)
have significantly more unique WNV genomes per cell than those that have lower viremias (robins). Aim 3 will
assess whether this also may occur in mosquitoes. We also will assess the degree to which this phenomenon
may allow for the maintenance of low fitness viral genotypes while preventing those of high fitness from gaining
dominance. Preliminary data supporting the feasibility of these studies is provided in the application.
The significance of this work is that it will provide novel, comprehensive data on the ways that changing
environmental conditions such as those that we are now experiencing may alter the fundamental population
biology of arboviruses. Arboviruses are uniquely susceptible to these conditions because they must replicate in
mosquitoes. This is inherently significant. Our work is also significant because it will provide mechanistic data
on how viruses may maintain genetic diversity in the face of both selective and stochastic reductions in genetic
diversity. Finally, the significance of our work is that we have provided technical and analytical tools that are
broadly useful and have permitted us to collaborate effectively with a wide array of investigators. The proposed
studies are technically and conceptually innovative because of the ways that we can combine realistic
transmission systems in the lab with barcoded viruses, single cell approaches, and other new molecular tools.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Address><Alpha Virus><Antibodies><Arboviral><Arboviruses><Arthropod-Borne Viruses><Aves><Avian><Bar Codes><Biology><Biometrics><Biometry><Bionomics><Biostatistics><Birds><CHIKV><COVID-19 virus><COVID19 virus><Cell Body><Cells><Chikungunya virus><CoV-2><CoV2><Collaborations><Competence><Crows><Culex><Culex (Genus)><Culicidae><DNA Molecular Biology><Data><Disease><Disease Outbreaks><Disorder><Ecology><Egypt 101 virus><Environment><Evolution><Face><Feasibility Studies><Flaviviridae><Flavivirus><Flavivirus Infections><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Funding><Future><Genetic Diversity><Genetic Variation><Genome><Genotype><Geography><Goals><Group A Arboviruses><Group B Arbovirus><Health><Human><Humanities><Incubated><Individual><Infection><Insecticide Resistance><Investigators><Knowledge><Literature><Maintenance><Medicine><Midgut><Modern Man><Molecular><Molecular Biology><Mosquitoes><Natural Selections><Nature><Nucleotides><Orthoflavivirus><Outbreaks><Phase><Population><Population Biology><Population Genetics><Population Heterogeneity><Predisposition><Public Health><RNA Sequences><RNA Viruses><Research><Research Personnel><Researchers><Robin><Robin bird><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Salivary Glands><Salivary Glands Head and Neck><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Shapes><Susceptibility><System><Temperature><Testing><Time><Togaviridae><Togaviruses><Transmission><Urbanization><Vaccines><Variant><Variation><Vertebrate Animals><Vertebrates><Viral Genetics><Viremia><Virion><Virus><Virus Particle><WNV><West Nile virus><Work><Wuhan coronavirus><ZIKV><Zika Virus><analytical tool><arthropod transmission><arthropod transmitted><arthropod-borne><arthropodborne><barcode><coronavirus disease 2019 virus><coronavirus disease-19 virus><diverse populations><environmental change><experience><faces><facial><fitness><flow cytophotometry><hCoV19><heterogeneous population><innovate><innovation><innovative><insecticide resistant><land use><multidisciplinary><mutant><nCoV2><novel><population diversity><prevent><preventing><social role><theories><tool><transmission process><vector><vector competence><vector mosquito><vectorial competence><vertebrata><viraemia><viral fitness><viral sepsis><virology><virus genetics><virusemia><zikav>