Venezuelan Equine Encephalitis

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Scott C. Weaver - One of the best experts on this subject based on the ideXlab platform.

  • Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose
    Vaccines, 2020
    Co-Authors: Shannan L. Rossi, Kasi E. Russell-lodrigue, Kenneth S. Plante, Nicholas A. Bergren, Rodion Gorchakov, Chad J. Roy, Scott C. Weaver
    Abstract:

    Venezuelan Equine Encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan Equine Encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replicated in the mosquito vector. Here we describe the use of a serotype ID VEEV (ZPC-738) vaccine with an internal ribosome entry site (IRES) to alter gene expression patterns. This ZPC/IRES vaccine was genetically engineered in two ways based on the position of the IRES insertion to create a vaccine that is safe and efficacious. After a single dose, both versions of the ZPC/IRES vaccine elicited neutralizing antibody responses in mice and non-human primates after a single dose, with more robust responses produced by version 2. Further, all mice and primates were protected from viremia following VEEV challenge. These vaccines were also safer in neonatal mice than the current investigational new drug vaccine, TC-83. These results show that IRES-based attenuation of alphavirus genomes consistently produce promising vaccine candidates, with VEEV/IRES version 2 showing promise for further development.

  • Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses.
    PloS one, 2016
    Co-Authors: Shea N. Gardner, Scott C. Weaver, Naomi L Forrester, Kevin Mcloughlin, Jonathan E. Allen, Mathilde Guerbois, Crystal Jaing
    Abstract:

    Venezuelan Equine Encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its Equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broad panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Finally, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.

  • ires based Venezuelan Equine Encephalitis vaccine candidate elicits protective immunity in mice
    Virology, 2013
    Co-Authors: Shannan L. Rossi, Naomi L Forrester, Kenneth S. Plante, Rodion Gorchakov, Mathilde Guerbois, Scott C. Weaver
    Abstract:

    Venezuelan Equine Encephalitis virus (VEEV) is an arbovirus that causes periodic outbreaks that impact Equine and human populations in the Americas. One of the VEEV subtypes located in Mexico and Central America (IE) has recently been recognized as an important cause of Equine disease and death, and human exposure also appears to be widespread. Here, we describe the use of an Internal Ribosome Entry Site (IRES) from encephalomyocarditis virus to stably attenuate VEEV, creating a vaccine candidate independent of unstable point mutations. Mice infected with this virus produced antibodies and were protected against lethal VEEV challenge. This IRES-based vaccine was unable to establish productive infection in mosquito cell cultures or in intrathoracically injected Aedes taeniorhynchus, demonstrating that it cannot be transmitted from a vaccinee. These attenuation, efficacy and safety results justify further development for humans or equids of this new VEEV vaccine candidate.

  • vaccines for Venezuelan Equine Encephalitis
    Vaccine, 2009
    Co-Authors: Slobodan Paessler, Scott C. Weaver
    Abstract:

    Arboviruses are capable of causing Encephalitis in animals and human population when transmitted by the vector or potentially via infectious aerosol. Recent re-emergence of Venezuelan Equine Encephalitis virus (VEEV) in South America emphasizes the importance of this pathogen to public health and veterinary medicine. Despite its importance no antivirals or vaccines against VEEV are currently available in the USA. Here we review some of the older and newer approaches aimed at generating a safe and immunogenic vaccine as well as most recent data about the mechanistic of protection in animal models of infection.

  • Venezuelan Equine Encephalitis virus infection of cotton rats.
    Emerging infectious diseases, 2007
    Co-Authors: Anne Sophie Carrara, Lark L. Coffey, Patricia V Aguilar, Abelardo C. Moncayo, Amelia P. A. Travassos Da Rosa, Márcio Roberto Teixeira Nunes, Robert B. Tesh, Scott C. Weaver
    Abstract:

    Venezuelan Equine Encephalitis virus (VEEV) is an emerging pathogen of equids and humans, but infection of its rodent reservoir hosts has received little study. To determine whether responses to infection vary among geographic populations, we inoculated 3 populations of cotton rats with 2 enzootic VEEV strains (Co97-0054 [enzootic ID subtype] and 68U201 [enzootic IE subtype]). The 3 populations were offspring from wild-caught cotton rats collected in a VEE-enzootic area of south Florida, USA; wild-caught cotton rats from a non–VEE-enzootic area of Texas, USA; and commercially available (Harlan) colony-reared cotton rats from a non–VEE-enzootic region. Although each population had similar early viremia titers, no detectable disease developed in the VEE-sympatric Florida animals, but severe disease and death affected the Texas and Harlan animals. 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.

George V. Ludwig - One of the best experts on this subject based on the ideXlab platform.

  • Testosterone Correlates with Venezuelan Equine Encephalitis Virus in Macaques
    2006
    Co-Authors: Michael P. Muehlenbein, Frank B. Cogswell, Mark A. James, James Koterski, George V. Ludwig
    Abstract:

    Abstract : Here we briefly report testosterone and cytokine responses to Venezuelan Equine Encephalitis virus (VEEV) in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  • Testosterone correlates with Venezuelan Equine Encephalitis virus infection in macaques
    Virology Journal, 2006
    Co-Authors: Michael P. Muehlenbein, Frank B. Cogswell, Mark A. James, James Koterski, George V. Ludwig
    Abstract:

    Here we briefly report testosterone and cytokine responses to Venezuelan Equine Encephalitis virus (VEEV) in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  • Venezuelan Equine Encephalitis Virus, Southern Mexico
    Emerging Infectious Diseases, 2004
    Co-Authors: Jose G. Estrada-franco, Roberto Navarro-lopez, Jerome E. Freier, Dionicio Cordova, Tamara Clements, Abelardo C. Moncayo, Wenli Kang, Carlos Hugo Gómez-hernández, Gabriela Rodríguez-domínguez, George V. Ludwig
    Abstract:

    Equine epizootics of Venezuelan Equine Encephalitis (VEE) occurred in the southern Mexican states of Chiapas in 1993 and Oaxaca in 1996. To assess the impact of continuing circulation of VEE virus (VEEV) on human and animal populations, serologic and viral isolation studies were conducted in 2000 to 2001 in Chiapas State. Human serosurveys and risk analyses indicated that long-term endemic transmission of VEEV occurred among villages with seroprevalence levels of 18% to 75% and that medical personnel had a high risk for VEEV exposure. Seroprevalence in wild animals suggested cotton rats as possible reservoir hosts in the region. Virus isolations from sentinel animals and genetic characterizations of these strains indicated continuing circulation of a subtype IE genotype, which was isolated from Equines during the recent VEE outbreaks. These data indicate long-term enzootic and endemic VEEV circulation in the region and continued risk for disease in Equines and humans.

  • endemic Venezuelan Equine Encephalitis in northern peru
    Emerging Infectious Diseases, 2004
    Co-Authors: Patricia V Aguilar, Gladys Medina, Lark L. Coffey, Abelardo C. Moncayo, George V. Ludwig, Michael J. Turell, Ivorlyne P Greene, Michael Anishchenko, Monica L Oguinn
    Abstract:

    Since Venezuelan Equine Encephalitis virus (VEEV) was isolated in Peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the Amazon region. To investigate genetic relationships among the Peru VEEV isolates and between the Peru isolates and other VEEV strains, a fragment of the PE2 gene was amplified and analyzed by single-stranded conformation polymorphism. Representatives of seven genotypes underwent sequencing and phylogenetic analysis. The results identified four VEE complex lineages that cocirculate in the Amazon region: subtypes ID (Panama and Colombia/Venezuela genotypes), IIIC, and a new, proposed subtype IIID, which was isolated from a febrile human, mosquitoes, and spiny rats. Both ID lineages and the IIID subtype are associated with febrile human illness. Most of the subtype ID isolates belonged to the Panama genotype, but the Colombia/Venezuela genotype, which is phylogenetically related to epizootic strains, also continues to circulate in the Amazon basin.

  • Short report: Isolation and identification of Venezuelan Equine Encephalitis virus from a human in Panama.
    The American journal of tropical medicine and hygiene, 2002
    Co-Authors: Joseph A. Mangiafico, Cindy A Rossi, George V. Ludwig
    Abstract:

    Venezuelan Equine Encephalitis (VEE) virus was isolated from a febrile human in Panama. The patient became febrile approximately 10 days after returning from Gatun Lake in Panama. The virus was isolated from the acute phase serum and identified as VEE, subtype ID virus by monoclonal antibodies, and was confirmed by cross plaque-reduction neutralization tests.

Michael D Parker - One of the best experts on this subject based on the ideXlab platform.

  • genetically engineered live attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent ie strain of Venezuelan Equine Encephalitis virus
    Vaccine, 2005
    Co-Authors: Douglas S Reed, William D. Pratt, Cathleen M Lind, Lawrence J Sullivan, Matthew G Lackemeyer, Michael D Parker
    Abstract:

    Abstract Two live, attenuated strains of Venezuelan Equine Encephalitis virus (VEE), IE1150K and V3526, were administered to macaques to determine if they could elicit protection against an aerosol challenge with virulent VEE virus of the IE variety (VEEV-IE). These viruses were rescued from full-length cDNA clones of 68U201 (VEEV-IE variety) and Trinidad donkey (VEEV-IA/B variety), respectively, and both have a furin cleavage site deletion mutation and a second-site resuscitating mutation. Both vaccines elicited neutralizing antibodies to viruses of the homologous variety but not to viruses of the heterologous variety. Eight weeks after vaccination, the macaques were challenged by aerosol exposure to virulent 68U201. Macaques vaccinated with V3526 were protected as well as macaques inoculated with IE1009, the wild-type infectious clone of 68U201. However, IE1150K failed to significantly protect macaques relative to controls. V3526 has now been shown to protect macaques against both IA/B [Pratt WD, Davis NL, Johnston RE, Smith JF. Genetically engineered, live attenuated vaccines for Venezuelan Equine Encephalitis: testing in animal models. Vaccine 2003;21(25–26):3854–62] and IE strains of VEE viruses.

  • aerosol infection of cynomolgus macaques with enzootic strains of Venezuelan Equine Encephalitis viruses
    The Journal of Infectious Diseases, 2004
    Co-Authors: Douglas S Reed, William D. Pratt, Cathleen M Lind, Lawrence J Sullivan, Michael D Parker
    Abstract:

    Because Venezuelan Equine Encephalitis viruses (VEEVs) are infectious by aerosol, they are considered to be a biological-weapons threat. Nonhuman-primate models are needed to evaluate the efficacy of candidate vaccines. In the present study, cynomolgus macaques, after aerosol exposure to either VEEV-IE or VEEV-IIIA, developed fever, viremia, and lymphopenia; the severity of the fever response, viremia, and lymphopenia correlated with the inhaled dose of VEEV. Of the 10 macaques in our study, 7 developed clinical signs indicative of Encephalitis, including loss of balance and hypothermia. In the macaque, the enzootic strains used are infectious by aerosol and lead to disease, including clinical Encephalitis.

Robert J. Phillpotts - One of the best experts on this subject based on the ideXlab platform.

Gladys Medina - One of the best experts on this subject based on the ideXlab platform.

  • Postepizootic Persistence of Venezuelan Equine Encephalitis Virus, Venezuela
    Emerging Infectious Diseases, 2005
    Co-Authors: Juan Carlos Navarro, Gladys Medina, Clovis Vasquez, Alexander Suárez, Hernán Biord, Marlene Salas, Lark L. Coffey, Eryu Wang, Scott C. Weaver
    Abstract:

    Five years after the apparent end of the major 1995 Venezuelan Equine Encephalitis (VEE) epizootic/epidemic, focal outbreaks of Equine Encephalitis occurred in Carabobo and Barinas States of western Venezuela. Virus isolates from horses in each location were nearly identical in sequence to 1995 isolates, which suggests natural persistence of subtype IC VEE virus (VEEV) strains in a genetically stable mode. Serologic evidence indicated that additional outbreaks occurred in Barinas State in 2003. Field studies identified known Culex (Melanoconion) spp. vectors and reservoir hosts of enzootic VEEV but a dearth of typical epidemic vectors. Cattle serosurveys indicated the recent circulation of enzootic VEEV strains, and possibly of epizootic strains. Persistence of VEEV subtype IC strains and infection of horses at the end of the rainy season suggest the possibility of an alternative, cryptic transmission cycle involving survival through the dry season of infected vectors or persistently infected vertebrates.

  • endemic Venezuelan Equine Encephalitis in northern peru
    Emerging Infectious Diseases, 2004
    Co-Authors: Patricia V Aguilar, Gladys Medina, Lark L. Coffey, Abelardo C. Moncayo, George V. Ludwig, Michael J. Turell, Ivorlyne P Greene, Michael Anishchenko, Monica L Oguinn
    Abstract:

    Since Venezuelan Equine Encephalitis virus (VEEV) was isolated in Peru in 1942, >70 isolates have been obtained from mosquitoes, humans, and sylvatic mammals primarily in the Amazon region. To investigate genetic relationships among the Peru VEEV isolates and between the Peru isolates and other VEEV strains, a fragment of the PE2 gene was amplified and analyzed by single-stranded conformation polymorphism. Representatives of seven genotypes underwent sequencing and phylogenetic analysis. The results identified four VEE complex lineages that cocirculate in the Amazon region: subtypes ID (Panama and Colombia/Venezuela genotypes), IIIC, and a new, proposed subtype IIID, which was isolated from a febrile human, mosquitoes, and spiny rats. Both ID lineages and the IIID subtype are associated with febrile human illness. Most of the subtype ID isolates belonged to the Panama genotype, but the Colombia/Venezuela genotype, which is phylogenetically related to epizootic strains, also continues to circulate in the Amazon basin.

  • Ecological studies of enzootic Venezuelan Equine Encephalitis in north-central Venezuela, 1997-1998.
    The American Journal of Tropical Medicine and Hygiene, 2001
    Co-Authors: Rosa Alba Salas, Gladys Medina, Clovis Vasquez, Roberto Barrera, Juan Carlos Navarro, Carmen Z. García, Jonathan Liria, Zoraida Fernández, Scott C. Weaver
    Abstract:

    From 1997-1998, we investigated the possible continuous circulation of epizootic Venezuelan Equine Encephalitis (VEE) virus suggested by a 1983 subtype IC interepizootic mosquito isolate made in Panaquire, Miranda State, Venezuela. The study area was originally covered by lowland tropical rainforest but has been converted into cacao plantations. Sentinel hamsters, small mammal trapping, mosquito collections, and human serosurveys were used to detect active or recent virus circulation. Six strains of subtype ID VEE virus were isolated from hamsters that displayed no apparent disease. Four other arboviruses belonging to group A (Togaviridae: Alphavirus), two Bunyamwera group (Bunyaviridae), and three Gamboa group (Bunyaviridae) arboviruses were also isolated from hamsters, as well as 8 unidentified viruses. Venezuelan Equine Encephalitis-specific antibodies were detected in 5 small mammal species: Proechimys guairae, Marmosa spp., and Didelphis marsupialis. Mosquito collections comprised of 38 different species, including 8 members of the subgenus Culex (Melanoconion), did not yield any virus isolates. Sera from 195 humans, either workers in the cacao plantation or nearby residents, were all negative for VEE virus antibodies. Sequences of 1,677 nucleotides from the P62 gene of 2 virus isolates indicated that they represent a subtype ID lineage that is distinct from all others characterized previously, and are unrelated to epizootic VEE emergence.

  • Emergence of a new epidemic/epizootic Venezuelan Equine Encephalitis virus in South America
    Proceedings of the National Academy of Sciences of the United States of America, 1995
    Co-Authors: Rebeca Rico-hesse, Gladys Medina, Scott C. Weaver, Julieta De Siger, Rosa Alba Salas
    Abstract:

    One of the most important questions in arbovirology concerns the origin of epidemic Venezuelan Equine Encephalitis (VEE) viruses; these viruses caused periodic, extensive epidemics/epizootics in the Americas from 1938-1973 (reaching the United States in 1971) but had recently been presumed extinct. We have documented the 1992 emergence of a new epidemic/epizootic VEE virus in Venezuela. Phylogenetic analysis of strains isolated during two outbreaks indicated that the new epidemic/epizootic virus(es) evolved recently from an enzootic VEE virus in northern South America. These results suggest continued emergence of epizootic VEE viruses; surveillance of enzootic viruses and routine vaccination of Equines should therefore be resumed.

  • emergence of a new epidemic epizootic Venezuelan Equine Encephalitis virus in south america
    Proceedings of the National Academy of Sciences of the United States of America, 1995
    Co-Authors: Rebeca Ricohesse, Gladys Medina, Scott C. Weaver, Julieta De Siger, Rosa Alba Salas
    Abstract:

    One of the most important questions in arbovirology concerns the origin of epidemic Venezuelan Equine Encephalitis (VEE) viruses; these viruses caused periodic, extensive epidemics/epizootics in the Americas from 1938-1973 (reaching the United States in 1971) but had recently been presumed extinct. We have documented the 1992 emergence of a new epidemic/epizootic VEE virus in Venezuela. Phylogenetic analysis of strains isolated during two outbreaks indicated that the new epidemic/epizootic virus(es) evolved recently from an enzootic VEE virus in northern South America. These results suggest continued emergence of epizootic VEE viruses; surveillance of enzootic viruses and routine vaccination of Equines should therefore be resumed.