Eastern equine encephalitis

Nathanson, Neal; Stolley, P.; Boolukos, P.J.

doi:10.1016/0021-9975(69)90034-6

Cited by 36 publications

(4 citation statements)

References 10 publications

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“…The pathological lesions in the CNS of the NA EEEV-infected marmosets were similar to those described for human cases[51-54], where EEEV causes neuronal loss, neuronophagia, perivascular cuffs, focal and diffuse accumulations of inflammatory cells and leptomeningitis in the CNS. Vascular lesions with breakdown in the structure of the vessel wall and the appearance of thrombi and extravasation of red blood cells have often been noted.…”

Section: Marmoset As a Model For Encephalitissupporting

confidence: 75%

An animal model that reflects human disease: the common marmoset (Callithrix jacchus)

Carrión

Patterson

2012

Current Opinion in Virology

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Highlights ► The common marmoset is a new world primate weighing between 350 and 400 g. ► Marmosets are exquisite NHP models for viral, protozoan, bacterial agents as well as prions. ► Marmosets have emerged as a viable model for studying high biocontainment pathogens. ► Models have been described for Ebola, Marburg, Lassa, SARS-CoA and EEE viruses. ► Use of marmosets will accelerate development of countermeasures to high consequence pathogens.

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Section: Marmoset As a Model For Encephalitissupporting

confidence: 75%

An animal model that reflects human disease: the common marmoset (Callithrix jacchus)

Carrión

Patterson

2012

Current Opinion in Virology

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“…The effect of inhalational EEEV infection has been assessed in both rhesus and cynomolgus macaque nonhuman primate species and in equine models [ 17 , 26 ]. Nathanson and colleagues infected juvenile rhesus macaques with a North American strain of EEEV via the intranasal route and produced fatal encephalitis [ 26 ]. However, further characterization of the rhesus model with adult primates or using the aerosol route of infection has never been addressed.…”

Section: Discussionmentioning

confidence: 99%

Characterization and pathogenesis of aerosolized eastern equine encephalitis in the common marmoset (Callithrix jacchus)

Porter

Erwin-Cohen

Twenhafel³

et al. 2017

Virol J

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BackgroundLicensed antiviral therapeutics and vaccines to protect against eastern equine encephalitis virus (EEEV) in humans currently do not exist. Animal models that faithfully recapitulate the clinical characteristics of human EEEV encephalitic disease, including fever, drowsiness, anorexia, and neurological signs such as seizures, are needed to satisfy requirements of the Food and Drug Administration (FDA) for clinical product licensing under the Animal Rule.MethodsIn an effort to meet this requirement, we estimated the median lethal dose and described the pathogenesis of aerosolized EEEV in the common marmoset (Callithrix jacchus). Five marmosets were exposed to aerosolized EEEV FL93-939 in doses ranging from 2.4 × 101 PFU to 7.95 × 105 PFU.ResultsThe median lethal dose was estimated to be 2.05 × 102 PFU. Lethality was observed as early as day 4 post-exposure in the highest-dosed marmoset but animals at lower inhaled doses had a protracted disease course where humane study endpoint was not met until as late as day 19 post-exposure. Clinical signs were observed as early as 3 to 4 days post-exposure, including fever, ruffled fur, decreased grooming, and leukocytosis. Clinical signs increased in severity as disease progressed to include decreased body weight, subdued behavior, tremors, and lack of balance. Fever was observed as early as day 2–3 post-exposure in the highest dose groups and hypothermia was observed in several cases as animals became moribund. Infectious virus was found in several key tissues, including brain, liver, kidney, and several lymph nodes. Clinical hematology results included early neutrophilia, lymphopenia, and thrombocytopenia. Key pathological changes included meningoencephalitis and retinitis. Immunohistochemical staining for viral antigen was positive in the brain, retina, and lymph nodes. More intense and widespread IHC labeling occurred with increased aerosol dose.ConclusionWe have estimated the medial lethal dose of aerosolized EEEV and described the pathology of clinical disease in the marmoset model. The results demonstrate that the marmoset is an animal model suitable for emulation of human EEEV disease in the development of medical countermeasures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-017-0687-7) contains supplementary material, which is available to authorized users.

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“…To further evaluate the construct validity of the structural damage in the context of virus infection, previous histopathology reports of encephalitic alphavirus infection in horses ( Monlux and Luedke, 1973 ; Monath et al, 1981 ; Del Piero et al, 2001 ; Silva et al, 2011 ), guinea pigs ( Roy et al, 2009 ), deer ( Kiupel et al, 2013 ), and nonhuman primates ( Nathanson et al, 1969 ) were examined. These reports identified virus in the thalamus and thalamic damage as a result of infection similar to what is described in this study.…”

Section: Discussionmentioning

confidence: 99%

“…These reports identified virus in the thalamus and thalamic damage as a result of infection similar to what is described in this study. In fact, virus has been detected in the thalamus of lethal human cases ( Nathanson et al, 1969 ; Luby et al, 1971 ). However, due to the lethality of the virus, these previous reports were only able to evaluate the results of acute infection leading to death and did not look at the long-term effects of infection in this region and in the host, such as PPI, ASR, and other behavioral outcomes.…”

Section: Discussionmentioning

confidence: 99%

Mouse Model of Neurological Complications Resulting from Encephalitic Alphavirus Infection

et al. 2017

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Long-term neurological complications, termed sequelae, can result from viral encephalitis, which are not well understood. In human survivors, alphavirus encephalitis can cause severe neurobehavioral changes, in the most extreme cases, a schizophrenic-like syndrome. In the present study, we aimed to adapt an animal model of alphavirus infection survival to study the development of these long-term neurological complications. Upon low-dose infection of wild-type C57B/6 mice, asymptomatic and symptomatic groups were established and compared to mock-infected mice to measure general health and baseline neurological function, including the acoustic startle response and prepulse inhibition paradigm. Prepulse inhibition is a robust operational measure of sensorimotor gating, a fundamental form of information processing. Deficits in prepulse inhibition manifest as the inability to filter out extraneous sensory stimuli. Sensory gating is disrupted in schizophrenia and other mental disorders, as well as neurodegenerative diseases. Symptomatic mice developed deficits in prepulse inhibition that lasted through 6 months post infection; these deficits were absent in asymptomatic or mock-infected groups. Accompanying prepulse inhibition deficits, symptomatic animals exhibited thalamus damage as visualized with H&E staining, as well as increased GFAP expression in the posterior complex of the thalamus and dentate gyrus of the hippocampus. These histological changes and increased GFAP expression were absent in the asymptomatic and mock-infected animals, indicating that glial scarring could have contributed to the prepulse inhibition phenotype observed in the symptomatic animals. This model provides a tool to test mechanisms of and treatments for the neurological sequelae of viral encephalitis and begins to delineate potential explanations for the development of such sequelae post infection.

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Eastern equine encephalitis

Cited by 36 publications

References 10 publications

An animal model that reflects human disease: the common marmoset (Callithrix jacchus)

An animal model that reflects human disease: the common marmoset (Callithrix jacchus)

Characterization and pathogenesis of aerosolized eastern equine encephalitis in the common marmoset (Callithrix jacchus)

Mouse Model of Neurological Complications Resulting from Encephalitic Alphavirus Infection

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