The Use of Chimeric Venezuelan Equine Encephalitis Viruses as an Approach for the Molecular Identification of Natural Virulence Determinants

Powers, Ann M.; Brault, Aaron C.; Kinney, Richard M.; Weaver, Scott C.

doi:10.1128/jvi.74.9.4258-4263.2000

Cited by 36 publications

(44 citation statements)

References 36 publications

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“…Why IE1150K was unable to elicit as vigorous an immune response as V3526 is not clear, as data from mice suggested comparable or better immunogenicity and protection against VEEV-IE regardless of the route of challenge [17]. However, Powers et al [21] did show using a 68U201 infectious clone that the IE virus is much more sensitive to Type I interferon than is an IA/B virus. This sensitivity tracked with viremia titers and virulence in guinea pigs where the IE virus produced lower levels of viremia and was non-virulent and the IA/B virus produced higher levels of viremia and was virulent.…”

Section: Discussionmentioning

confidence: 99%

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

Reed

Lind

Lackemeyer

et al. 2005

Vaccine

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Section: Discussionmentioning

confidence: 99%

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

Reed

Lind

Lackemeyer

et al. 2005

Vaccine

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“…However, the presence of Ͼ70 amino acid differences in the PE2 (E2 precursor) genes of these subtypes precluded the identification specific residues in the vector infection phenotype. The 11% difference in structural protein amino acids between the IE and IAB serotypes (38) also indicates the possibility of intergenic incompatibilities in some chimeras (25).…”

Section: Discussionmentioning

confidence: 99%

“…To determine the potential role of specific nucleotide and͞or amino acid changes in the emergence of epizootic VEEV subtype IE viruses, the infectious cDNA clone of the enzootic IE strain 68U201 (pIE.AA) (25) was used for mutagenesis to incorporate all E2 amino acid differences between the epizootic VEEV subtype IE strain CPA201 and enzootic strain 68U201 (13). The mutants produced from the 68U201 backbone included all three amino acid differences in all possible combinations (single, double, and triple mutants; Table 3).…”

Section: Methodsmentioning

confidence: 99%

Venezuelan equine encephalitis emergence: Enhanced vector infection from a single amino acid substitution in the envelope glycoprotein

Brault¹,

Powers²,

Ortiz³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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160

137

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In 1993 and 1996, subtype IE Venezuelan equine encephalitis (VEE) virus caused epizootics in the Mexican states of Chiapas and Oaxaca. Previously, only subtype IAB and IC VEE virus strains had been associated with major outbreaks of equine and human disease. The IAB and IC epizootics are believed to emerge via adaptation of enzootic (sylvatic, equine-avirulent) strains for high titer equine viremia that results in efficient infection of mosquito vectors. However, experimental equine infections with subtype IE equine isolates from the Mexican outbreaks demonstrated neurovirulence but little viremia, inconsistent with typical VEE emergence mechanisms. Therefore, we hypothesized that changes in the mosquito vector host range might have contributed to the Mexican emergence. To test this hypothesis, we evaluated the susceptibility of the most abundant mosquito in the deforested Pacific coastal locations of the VEE outbreaks and a proven epizootic vector, Ochlerotatus taeniorhynchus. The Mexican epizootic equine isolates exhibited significantly greater infectivity compared with closely related enzootic strains, supporting the hypothesis that adaptation to an efficient epizootic vector contributed to disease emergence. Reverse genetic studies implicated a Ser 3 Asn substitution in the E2 envelope glycoprotein as the major determinant of the increased vector infectivity phenotype. Our findings underscore the capacity of RNA viruses to alter their vector host range through minor genetic changes, resulting in the potential for disease emergence.

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“…Virus titers were determined in blood and homogenized tissues by a conventional plaque assay as described previously (25). In accordance with the manufacturer's instructions, complete blood cell counts were performed on the collected blood samples with a VetScan HMT machine (Abaxis, Inc., Union City, CA) and biochemical analyses were performed on the plasma samples with a mammalian liver enzyme profile rotor on a VetScan analyzer (Abaxis, Inc., Union City, CA).…”

Section: Methodsmentioning

confidence: 99%

Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains

Adams

Aronson

Tardif

et al. 2008

J Virol

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Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log 10 PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.

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The Use of Chimeric Venezuelan Equine Encephalitis Viruses as an Approach for the Molecular Identification of Natural Virulence Determinants

Cited by 36 publications

References 36 publications

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

Venezuelan equine encephalitis emergence: Enhanced vector infection from a single amino acid substitution in the envelope glycoprotein

Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains

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