Quasispecies dynamics in arborvirus persistence, emergence and fitness

Summary

Principal Investigator: GREGORY DAVID EBEL
Affiliation: University of New Mexico
Country: USA
Abstract: Arthropod-borne viruses (arboviruses) continue to burden human health in spite of impressive advances in public health and medicine. The introduction of these agents into naive ecosystems presents an ongoing challenge. Our ability to predict whether these agents will persist once introduced and/or emerge as significant public health threats is hindered because we know very little about the underlying mechanisms that allow them to adapt to novel and/or changing environments. West Nile virus (WNV) exists in nature as a genetically diverse swarm of competing mutants that differ in varying degrees from a consensus sequence (i.e. as a quasispecies). Our long-term objective is to understand how arbovirus population dynamics are shaped by their transmission cycles, and how these host-virus interactions contribute to arbovirus persistence and emergence. Proposed studies will test the hypothesis that arbovirus quasispecies are associated with mode of transmission and in vivo phenotype. This hypothesis will be tested using WNV, which was recently introduced into North America, as a model system. We will incorporate a research strategy that takes advantage of pre-existing, well genetically characterized WNV populations, our ability to manipulate the WNV genome, and our ability to faithfully model the WNV transmission cycle in the laboratory. This work builds on preliminary studies showing that WNV exists in nature as a quasispecies, and that mosquitoes provide a source of genetic variation to WNV populations while birds limit this variation. Our specific aims are to (1) determine the impact of mosquito infection and transmission on the WNV quasispecies in mosquitoes, (2) to evaluate the impact of WNV genetic diversity on mosquito vector competence, avian infectivity and viremia, and pathogenesis in mice, and (3) to determine whether more genetically diverse WNV populations are more fit in mosquitoes and birds than less diverse populations. The results of these studies will enhance our basic understanding of the host-virus interactions that allow arboviruses to persist within complex transmission cycles and emerge as health threats.
Funding Period: ----------------2007 - ---------------2012-
more information: NIH RePORT

Top Publications

  1. pmc Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching
    Greta V S Jerzak
    Wadsworth Center, New York State Department of Health, 5668 State Farm Rd Slingerlands, NY 12159, USA
    Virology 374:256-60. 2008
  2. pmc The role of innate immunity in conditioning mosquito susceptibility to West Nile virus
    Abhishek N Prasad
    Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA
    Viruses 5:3142-70. 2013
  3. pmc MicroRNA levels are modulated in Aedes aegypti after exposure to Dengue-2
    C L Campbell
    Department of Microbiology, Immunology, and Pathology, Arthropod borne Infectious Diseases Laboratory, Colorado State University, Fort Collins, CO, USA
    Insect Mol Biol 23:132-9. 2014
  4. pmc Seroprevalence of Powassan virus in New England deer, 1979-2010
    Robert A Nofchissey
    University of New Mexico School of Medicine, Albuquerque, NM, USA
    Am J Trop Med Hyg 88:1159-62. 2013
  5. pmc Toward an activist agenda for monitoring virus emergence
    Gregory D Ebel
    Department of Microbiology Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1690 Campus Delivery, Fort Collins, CO 80523, USA Electronic address
    Cell Host Microbe 15:655-6. 2014
  6. ncbi Stable prevalence of Powassan virus in Ixodes scapularis in a northern Wisconsin focus
    Doug E Brackney
    University of New Mexico School of Medicine, Department of Pathology, Albuquerque, New Mexico 87131, USA
    Am J Trop Med Hyg 79:971-3. 2008
  7. pmc Population variation of West Nile virus confers a host-specific fitness benefit in mosquitoes
    Kelly A Fitzpatrick
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Virology 404:89-95. 2010
  8. pmc Fatal case of deer tick virus encephalitis
    Norma P Tavakoli
    Wadsworth Center, New York State Department of Health and the Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA
    N Engl J Med 360:2099-107. 2009
  9. pmc RNAi targeting of West Nile virus in mosquito midguts promotes virus diversification
    Doug E Brackney
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
    PLoS Pathog 5:e1000502. 2009
  10. pmc Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice
    Kendra N Pesko
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
    Virology 427:10-7. 2012

Scientific Experts

  • GREGORY DAVID EBEL
  • Norma P Tavakoli
  • Doug E Brackney
  • Etsuko Nonaka
  • Ann M Hess
  • Eleanor R Deardorff
  • Kendra N Pesko
  • Kelly A Fitzpatrick
  • Pei Yong Shi
  • Greta V S Jerzak
  • C L Campbell
  • Abhishek N Prasad
  • Robert A Nofchissey
  • Bo Zhang
  • Jaclyn C Scott
  • Laura D Kramer
  • T Harrison
  • Aaron C Brault
  • Angela Bosco-Lauth
  • Erica Berl
  • Louis A Magnarelli
  • John Paul Mutebi
  • Michael Anishchenko
  • Tia M Blevins
  • Charles Lubelczyk
  • Elizabeth M Ryan
  • Niall J Lennon
  • Matthew R Henn
  • Ruchi M Newman
  • Edward Bedrick
  • Fernando Torres-PĂ©rez
  • Brian Hjelle
  • Virginie Bondu-Hawkins
  • Kendra Pesko
  • Brian L Hjelle
  • Corey L Campbell
  • Ken E Olson
  • Carol D Blair
  • Ivy Brown

Detail Information

Publications19

  1. pmc Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching
    Greta V S Jerzak
    Wadsworth Center, New York State Department of Health, 5668 State Farm Rd Slingerlands, NY 12159, USA
    Virology 374:256-60. 2008
    ..Thus, the abundant genetic variation contributed to WNV populations through infection of mosquitoes and the strong purifying selection contributed by infection of birds may be maintained despite frequent host switching...
  2. pmc The role of innate immunity in conditioning mosquito susceptibility to West Nile virus
    Abhishek N Prasad
    Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA
    Viruses 5:3142-70. 2013
    ..We draw from the literature with respect to other virus-vector pairings to attempt to draw inferences to gaps in our knowledge about West Nile virus and relevant vectors. ..
  3. pmc MicroRNA levels are modulated in Aedes aegypti after exposure to Dengue-2
    C L Campbell
    Department of Microbiology, Immunology, and Pathology, Arthropod borne Infectious Diseases Laboratory, Colorado State University, Fort Collins, CO, USA
    Insect Mol Biol 23:132-9. 2014
    ..Together, these data are consistent with the hypothesis that profound and persistent changes to gene expression occur in DENV2-exposed mosquitoes...
  4. pmc Seroprevalence of Powassan virus in New England deer, 1979-2010
    Robert A Nofchissey
    University of New Mexico School of Medicine, Albuquerque, NM, USA
    Am J Trop Med Hyg 88:1159-62. 2013
    ..Evidence of exposure was detected in all three states. Overall our results demonstrate that seroprevalence is variable in time and space, suggesting that risk of exposure to Powassan virus is similarly variable...
  5. pmc Toward an activist agenda for monitoring virus emergence
    Gregory D Ebel
    Department of Microbiology Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1690 Campus Delivery, Fort Collins, CO 80523, USA Electronic address
    Cell Host Microbe 15:655-6. 2014
    ..Incorporating experimental evolutionary studies, as described in this issue by Stapleford et al. (2014), has the potential to move public health toward a more proactive agenda for predicting and responding to disease emergence...
  6. ncbi Stable prevalence of Powassan virus in Ixodes scapularis in a northern Wisconsin focus
    Doug E Brackney
    University of New Mexico School of Medicine, Department of Pathology, Albuquerque, New Mexico 87131, USA
    Am J Trop Med Hyg 79:971-3. 2008
    ..All isolated virus belonged to the DTV genotype of POWV. These findings suggest stable transmission of POWV in this focus over ten years and highlight the potential for this agent to emerge as a public health concern...
  7. pmc Population variation of West Nile virus confers a host-specific fitness benefit in mosquitoes
    Kelly A Fitzpatrick
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Virology 404:89-95. 2010
    ..Our results demonstrate that high genetic diversity leads to fitness gains in vector mosquitoes, but not chickens...
  8. pmc Fatal case of deer tick virus encephalitis
    Norma P Tavakoli
    Wadsworth Center, New York State Department of Health and the Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA
    N Engl J Med 360:2099-107. 2009
    ..This case demonstrates that deer tick virus can be a cause of fatal encephalitis...
  9. pmc RNAi targeting of West Nile virus in mosquito midguts promotes virus diversification
    Doug E Brackney
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
    PLoS Pathog 5:e1000502. 2009
    ..Further, they provide a mechanistic basis for the relative importance of mosquitoes in driving WNV diversification...
  10. pmc Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice
    Kendra N Pesko
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
    Virology 427:10-7. 2012
    ..Additionally, our findings suggest that highly similar mutants may frequently occur in particular vertebrate hosts...
  11. pmc West Nile virus experimental evolution in vivo and the trade-off hypothesis
    Eleanor R Deardorff
    Department of Pathology, University of New Mexico, Albuquerque, New Mexico, United States of America
    PLoS Pathog 7:e1002335. 2011
    ....
  12. pmc Nonconsensus West Nile virus genomes arising during mosquito infection suppress pathogenesis and modulate virus fitness in vivo
    Gregory D Ebel
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    J Virol 85:12605-13. 2011
    ..Overall, this work highlights the complex relationships that exist between individual and group phenotypes in RNA viruses and identifies RNA helicase as an attenuation and fitness determinant in WNV...
  13. pmc West Nile virus genetic diversity is maintained during transmission by Culex pipiens quinquefasciatus mosquitoes
    Doug E Brackney
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America
    PLoS ONE 6:e24466. 2011
    ..Together, these data suggest that the complexity of WNV populations are not significantly diminished during the extrinsic incubation period of mosquitoes...
  14. pmc Small RNA profiling of Dengue virus-mosquito interactions implicates the PIWI RNA pathway in anti-viral defense
    Ann M Hess
    Department of Statistics, Colorado State University, Fort Collins, Colorado 80523, USA
    BMC Microbiol 11:45. 2011
    ..aegypti, we deep-sequenced small non-coding RNAs. Triplicate biological replicates were used so that rigorous statistical metrics could be applied...
  15. pmc Homogeneity of Powassan virus populations in naturally infected Ixodes scapularis
    Doug E Brackney
    University of New Mexico School of Medicine, Department of Pathology, Albuquerque, New Mexico, USA
    Virology 402:366-71. 2010
    ..These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks...
  16. pmc Comparison of dengue virus type 2-specific small RNAs from RNA interference-competent and -incompetent mosquito cells
    Jaclyn C Scott
    Arthropod Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA
    PLoS Negl Trop Dis 4:e848. 2010
    ....
  17. pmc Persistence of pathogens with short infectious periods in seasonal tick populations: the relative importance of three transmission routes
    Etsuko Nonaka
    Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America
    PLoS ONE 5:e11745. 2010
    ..Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model...
  18. pmc Molecular epidemiology of Powassan virus in North America
    Kendra N Pesko
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
    J Gen Virol 91:2698-705. 2010
    ....
  19. pmc C6/36 Aedes albopictus cells have a dysfunctional antiviral RNA interference response
    Doug E Brackney
    Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
    PLoS Negl Trop Dis 4:e856. 2010
    ..These findings are analogous to the type-I interferon deficiency described in Vero (African green monkey kidney) cells and suggest that C6/36 cells may fail to accurately model mosquito-arbovirus interactions at the molecular level...