ECOLOGY AND GENETICS OF VENEZUELAN EQUINE ENCEPHALITIS

Summary

Principal Investigator: Scott Weaver
Abstract: DESCRIPTION: Venezuelan equine encephalitis (VEE) is an emerging arboviral disease and a public and veterinary health threat throughout the Americas, including the United States. Recent outbreaks in South America and Mexico underscore the continued threat of VEE emergence. VEE virus epitomizes the ability of RNA viruses to mutate and alter their host range and disease patterns, and represents ideal model systems for the study of RNA- and arboviral disease emergence. The seminal question in 60 years of VEE research has been the source of the strains responsible for major human and equine outbreaks. Our epidemiological and genetic studies indicate that epizootic, subtype LkB and IC epizootic viruses evolve from enzootic, subtype ID viruses that circulate continuously in Venezuela and Colombia. Reverse genetic studies indicate that small numbers of mutations can generate subtype IC strains from ID progenitors, and implicate positively charged E2 envelope glycoprotein amino acid changes in emergence of a 1992-93 outbreak. Field studies have identified the critical hosts of the progenitor enzootic transmission cycles, and satellite imagery has been developed to predict over a broad geographical range the locations where enzootic viruses circulate. Epidemiological and genetic data also suggest that epizootic viruses persist following the cessation of outbreaks, raising the possibility of VEE emergence without the need for mutation. All of these emergence scenarios have profound public health implications. Using a unique combination of infectious cDNA clone technology, experimental infections, and field studies, the proposed research will answer critical, remaining questions regarding VEE emergence: 1) do similar changes in the E2 glycoprotein explain the emergence of previous LkB and IC epizootic viruses; 2) are other genotypes of enzootic VEE viruses capable of mutating to become epizootic, or does the genetic backbone of the enzootic progenitor limit its ability to become equine virulent? 3) How are epizootic viruses, generated via mutation of enzootic strains in sylvatic habitats, transported to locations where ecological conditions permit the initiation of outbreaks? And, 4) do epizootic strains persist in continuous cycles following the cessation of outbreaks? Our results will advance understanding of VEE emergence mechanisms, and will predict locations of potential emergence in Latin America and Florida. This information will be invaluable in targeting prevention and control resources, especially for obtaining maximum benefit in developing countries with limited resources.
Funding Period: 2001-07-01 - 2007-05-31
more information: NIH RePORT

Top Publications

  1. pmc Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease
    Lark L Coffey
    Blood Systems Research Institute, Department of Laboratory Medicine University of California, San Francisco, San Francisco, CA 94118, USA
    Future Microbiol 8:155-76. 2013
  2. pmc Venezuelan equine encephalitis in Panama: fatal endemic disease and genetic diversity of etiologic viral strains
    Evelia Quiroz
    Gorgas Memorial Institute, Panama City, Panama
    PLoS Negl Trop Dis 3:e472. 2009
  3. ncbi Susceptibility of Ae. aegypti (Diptera: Culicidae) to infection with epidemic (subtype IC) and enzootic (subtypes ID, IIIC, IIID) Venezuelan equine encephalitis complex alphaviruses
    Diana I Ortiz
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 0609, USA
    J Med Entomol 45:1117-25. 2008
  4. pmc Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling
    Olga A Kolokoltsova
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
    Virology 377:133-42. 2008
  5. ncbi [Cibarial morphology in Psorophora Robineau-Desvoidy subgenera (Diptera: Culicidae)]
    Jonathan Liria
    Depto Biologia, Facultad Experimental de Ciencias y Tecnología, Univ de Carabobo, Venezuela
    Neotrop Entomol 36:902-9. 2007
  6. pmc Venezuelan equine encephalitis virus in the mosquito vector Aedes taeniorhynchus: infection initiated by a small number of susceptible epithelial cells and a population bottleneck
    Darci R Smith
    Department of Pathology and Center for Tropical Diseases, University of Texas Medical, Branch, Galveston, TX 77555 0609, USA
    Virology 372:176-86. 2008
  7. pmc Venezuelan equine encephalitis virus infection of cotton rats
    Anne Sophie Carrara
    Department of Pathology, University of Texas Medical Branch, Galveston 77555 0609, USA
    Emerg Infect Dis 13:1158-65. 2007
  8. ncbi Recombinant alphaviruses are safe and useful serological diagnostic tools
    Haolin Ni
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Am J Trop Med Hyg 76:774-81. 2007
  9. pmc Serologic evidence of widespread everglades virus activity in dogs, Florida
    Lark L Coffey
    University of Texas Medical Branch, Galveston, Texas 77555, USA
    Emerg Infect Dis 12:1873-9. 2006
  10. pmc Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation
    Michael Anishchenko
    Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 0609, USA
    Proc Natl Acad Sci U S A 103:4994-9. 2006

Scientific Experts

  • Scott Weaver
  • Lark L Coffey
  • Jonathan Liria
  • Slobodan Paessler
  • Michael Anishchenko
  • Darci R Smith
  • Diana I Ortiz
  • Anne Sophie Carrara
  • Eryu Wang
  • Robert B Tesh
  • Patricia V Aguilar
  • Ivorlyne P Greene
  • Juan Carlos Navarro
  • Evelia Quiroz
  • Olga A Kolokoltsova
  • Haolin Ni
  • Wenli Kang
  • Ilya Frolov
  • Dayaleth Alfonzo
  • Julio Cisneros
  • Robert A Davey
  • Joan L Kenney
  • A Paige Adams
  • Stanley J Watowich
  • Aaron M Domina
  • Andrey A Kolokoltsov
  • Marcio R T Nunes
  • Nadezhda E Yun
  • Ann M Powers
  • Michele A Zacks
  • Abelardo C Moncayo
  • Amelia P Travassos da Rosa
  • Amelia P A Travassos Da Rosa
  • Richard A Bowen
  • Laura Austgen
  • Cristina Ferro
  • James Olson
  • Aaron C Brault
  • Gladys Medina
  • Clovis Vasquez
  • Jose Estrada-Franco
  • Jorge Boshell
  • Alexander Suarez
  • Roberto Barrera
  • Judith Aronson
  • Patrick J Blair
  • Hernán Biord
  • Maria E Grillet
  • Gonzales Gonzales
  • Martin Pfeffer
  • Marlene Salas
  • Margarita Tamayo
  • Carolina Guevara

Detail Information

Publications19

  1. pmc Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease
    Lark L Coffey
    Blood Systems Research Institute, Department of Laboratory Medicine University of California, San Francisco, San Francisco, CA 94118, USA
    Future Microbiol 8:155-76. 2013
    ....
  2. pmc Venezuelan equine encephalitis in Panama: fatal endemic disease and genetic diversity of etiologic viral strains
    Evelia Quiroz
    Gorgas Memorial Institute, Panama City, Panama
    PLoS Negl Trop Dis 3:e472. 2009
    ..These findings underscore endemic VEE as an important but usually neglected arboviral disease of Latin America...
  3. ncbi Susceptibility of Ae. aegypti (Diptera: Culicidae) to infection with epidemic (subtype IC) and enzootic (subtypes ID, IIIC, IIID) Venezuelan equine encephalitis complex alphaviruses
    Diana I Ortiz
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 0609, USA
    J Med Entomol 45:1117-25. 2008
    ..The occurrence of enzootic VEE complex viruses circulating endemically in Iquitos suggests the possibility of a dengue-like transmission cycle among humans in tropical cities...
  4. pmc Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling
    Olga A Kolokoltsova
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
    Virology 377:133-42. 2008
    ..This work highlights novel host cell determinants required for alphavirus pathogenesis and suggests that RAS signalling may play an important role in neuronal susceptibility to SINV infection...
  5. ncbi [Cibarial morphology in Psorophora Robineau-Desvoidy subgenera (Diptera: Culicidae)]
    Jonathan Liria
    Depto Biologia, Facultad Experimental de Ciencias y Tecnología, Univ de Carabobo, Venezuela
    Neotrop Entomol 36:902-9. 2007
    ..We suggest to include those diagnostic characters in the future taxonomic and systematic studies in the genus Psorophora...
  6. pmc Venezuelan equine encephalitis virus in the mosquito vector Aedes taeniorhynchus: infection initiated by a small number of susceptible epithelial cells and a population bottleneck
    Darci R Smith
    Department of Pathology and Center for Tropical Diseases, University of Texas Medical, Branch, Galveston, TX 77555 0609, USA
    Virology 372:176-86. 2008
    ..These results indicate that the structural proteins determine initial infection of a small number of midgut cells, and that VEEV undergoes population bottlenecks during vector infection...
  7. pmc Venezuelan equine encephalitis virus infection of cotton rats
    Anne Sophie Carrara
    Department of Pathology, University of Texas Medical Branch, Galveston 77555 0609, USA
    Emerg Infect Dis 13:1158-65. 2007
    ..Our findings suggest that the geographic origins of cotton rats are important determinants of the outcome of VEE infection and reservoir potential of these rodents...
  8. ncbi Recombinant alphaviruses are safe and useful serological diagnostic tools
    Haolin Ni
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Am J Trop Med Hyg 76:774-81. 2007
    ..Chimeric viruses were produced efficiently in cell culture and were as effective as the parental virus for identifying infection of humans, horses, and rodents in these serological assays...
  9. pmc Serologic evidence of widespread everglades virus activity in dogs, Florida
    Lark L Coffey
    University of Texas Medical Branch, Galveston, Texas 77555, USA
    Emerg Infect Dis 12:1873-9. 2006
    ..These results indicate that EVEV is widespread in Florida and may be an important, unrecognized cause of human illness...
  10. pmc Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation
    Michael Anishchenko
    Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 0609, USA
    Proc Natl Acad Sci U S A 103:4994-9. 2006
    ..VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses...
  11. pmc Postepizootic persistence of Venezuelan equine encephalitis virus, Venezuela
    Juan Carlos Navarro
    Universidad Central de Venezuela, Caracas, Venezuela
    Emerg Infect Dis 11:1907-15. 2005
    ....
  12. ncbi Susceptibility of Psorophora confinnis (Diptera: Culicidae) to infection with epizootic (subtype IC) and enzootic (subtype ID) Venezuelan Equine encephalitis viruses
    Diana I Ortiz
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 0609, USA
    J Med Entomol 42:857-63. 2005
    ..Nonetheless, its high susceptibility, abundance in enzootic and epizootic regions, and feeding behavior suggest that Ps. confinnis is an important bridge vector for both enzootic and epizootic VEEV...
  13. ncbi Susceptibility of Ochlerotatus taeniorhynchus and Culex nigripalpus for Eeverglades virus
    Lark L Coffey
    Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Am J Trop Med Hyg 73:11-6. 2005
    ..Identification of vectors involved in enzootic EVEV transmission will assist in understanding potential changes in vector use that could accompany the emergence of epizootic or epidemic EVEV...
  14. ncbi A novel, rapid assay for detection and differentiation of serotype-specific antibodies to Venezuelan equine encephalitis complex alphaviruses
    Eryu Wang
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555 0609, USA
    Am J Trop Med Hyg 72:805-10. 2005
    ..It could also be used to determine the epidemic potential of a VEE virus following an intentional introduction for bioterrorism...
  15. ncbi Ecological characterization of the aquatic habitats of mosquitoes (Diptera: Culicidae) in enzootic foci of Venezuelan equine encephalitis virus in western Venezuela
    Dayaleth Alfonzo
    Instituto de Zoologia Tropical, Universidad Central de Venezuela, Caracas 1041 A, Venezuela
    J Med Entomol 42:278-84. 2005
    ..These results allowed us to interpret better our previous studies on mosquito adult spread in the study area and their possible role as VEEV disseminators...
  16. pmc Venezuelan equine encephalitis virus infection of spiny rats
    Anne Sophie Carrara
    University of Texas Medical Branch, Galveston, Texas, USA
    Emerg Infect Dis 11:663-9. 2005
    ....
  17. ncbi Venezuelan equine encephalitis virus in the guinea pig model: evidence for epizootic virulence determinants outside the E2 envelope glycoprotein gene
    Ivorlyne P Greene
    Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555 0609, USA
    Am J Trop Med Hyg 72:330-8. 2005
    ..However, early replication in lymphoid tissues appeared to be primarily envelope dependent...