Aerosol Exposure to Western Equine Encephalitis Virus Causes Fever and Encephalitis in Cynomolgus Macaques

Reed, Douglas S.; Larsen, Tom; Sullivan, Lawrence J.; Lind, Cathleen M.; Lackemeyer, Matthew G.; Pratt, William D.; Parker, Michael D.

doi:10.1086/444397

Cited by 87 publications

(68 citation statements)

References 15 publications

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“…Macaques developed fever within 4-5 days as well as leukocytosis and hyperglycemia, which were accompanied by lesions in the brain, with WEEV antigens being identified in microglial cells and neurons. 45 As is typical of WEEV infection in humans, the lethality rate was low, with one of six animals in each of the high-and low-dose groups succumbing to disease.…”

Section: Path From Experimental Vaccines To Licensurementioning

confidence: 90%

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Wolfe

Heppner

Gardner

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure.

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Section: Path From Experimental Vaccines To Licensurementioning

confidence: 90%

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Wolfe

Heppner

Gardner

et al. 2014

The American Society of Tropical Medicine and Hygiene

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“…This species is often used for biomedical research [7,21] involving infectious diseases, such as AIDS [43], influenza [17], tuberculosis [6,15], measles virus [30], western equine encephalitis virus [27], and severe acute respiratory syndrome (SARS) [1�]� neuro- [1�]� neuro-� neurological diseases, such as Alzheimer's disease [40] and Parkinson's disease [8]� reproduction [33]� regenerative medicine [31]� transplantation [4,18,25,41,42]� and immunotherapy [22,32]. In order to effectively use cynomolgus macaques for medical research, it is necessary to better understand the genetic diversity among and within the different populations.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Diversity among Three Subpopulations of Cynomolgus Macaques (Macaca fascicularis) Originating from the Indochinese Region

et al. 2010

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Abstract:The cynomolgus macaque (Macaca fascicularis) has emerged as an important experimental animal model for biomedical research in various domains, necessitating the more extensive characterization of the genetic backgrounds influencing the macaque's response to drugs and sensitivity to experimental disease. The diversity of the variable mitochondrial DNA (mtDNA) D-loop region has been analyzed phylogenetically among geographically isolated populations or within subdivisions of the same regional population. However, the genetic differences among several substructures originating from a common population have not yet been investigated. By sequencing fragments of the mtDNA D-loop region from two subpopulations from the Indochinese region (Cambodian-Chinese and Vietnamese) along with two native Indonesian and Filipino populations, we identified 87 mtDNA D-loop haplotypes, of which 67 are new. The phylogenetic relationship suggests that the Indochinese haplotypes are intermingled in comparison to the distinct divergence of the Indonesian and Filipino lineages. The subpopulations were shown by estimation of evolutionary divergence and Wright's F-statistic (Fst) to have little genetic differentiation. Altogether, the subpopulations may be used in biomedical research, even though a slight difference is observed in haplotype frequencies among them. Therefore, genetic diversity analyses will be necessary for the elucidation of genetic differences among the populations, as well as to obtain a better understanding of genetic diversity for biomedical research. This will involve the selection of macaques and the monitoring of genetic heterogeneity among and within breeding facilities.

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“…Numerous isolates of WEEV have been obtained from humans and equines during the many outbreaks, and mosquito isolates have been recovered from both epidemic and interepidemic periods. Furthermore, because WEEV has been shown to be infectious by aerosol, it is a threat as a potential bioterrorist (BT) weapon (Froeschle, 1964;Liu et al, 1970;Reed et al, 2005;Sidwell & Smee, 2003). (Hahn et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model

Logue

Bosio

Welte

et al. 2009

Journal of General Virology

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Little is known about viral determinants of virulence associated with western equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV isolates in an outbred CD1 mouse model. Full genome sequence analyses showed ¡2.7 % divergence among the six WEEV isolates. However, the percentage mortality and mean time to death (MTD) varied significantly when mice received subcutaneous injections of 10 3 p.f.u. of each virus. Two WEEV strains, McMillan (McM) and Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality. McM had significantly higher titres in the brain than IMP. Similar differences in virulence were observed when McM and IMP were administered by aerosol, intranasal or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 10 3 p.f.u. of each virus was administered by intracerebral inoculation; in contrast, IMP caused no mortality. The presence of IMP in the brains after infection by different routes and the lack of observed mortality confirmed that IMP is neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity of brain lesions, virus distribution patterns, routes of infection and differences in infection of cultured cells, McM and IMP were identified as high-and low-virulence isolates, respectively.

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Aerosol Exposure to Western Equine Encephalitis Virus Causes Fever and Encephalitis in Cynomolgus Macaques

Cited by 87 publications

References 15 publications

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Mitochondrial DNA Diversity among Three Subpopulations of Cynomolgus Macaques (Macaca fascicularis) Originating from the Indochinese Region

Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model

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