Flavivirus Neurotropism, Neuroinvasion, Neurovirulence and Neurosusceptibility: Clues to Understanding Flavivirus- and Dengue-Induced Encephalitis

Velandia, Myriam L.; Castellanos, Jaime E.

doi:10.5772/26571

Cited by 6 publications

(8 citation statements)

References 116 publications

(94 reference statements)

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“…Other studies have highlighted the impact of specific polymorphisms on differences in pathogenesis and neurovirulence observed between different strains of HSV-1 [163,164]. The term neurovirulence is used to describe a virus’s ability to directly impact the nervous system and cause disease [165]. Neurovirulence is the sum total of multiple underlying components, which include the ability of a given virus strain to invade the nervous system (neuroinvasion), its cell-to-cell spread capabilities, the ability to replicate in neurons and cause overt disease, and its ability to reactivate from latency [49,166].…”

Section: Strain-specific Differences In Hsv-1 Neurovirulence and Tmentioning

confidence: 99%

Persistent Infection with Herpes Simplex Virus 1 and Alzheimer’s Disease—A Call to Study How Variability in Both Virus and Host may Impact Disease

Mangold

Szpara

2019

Viruses

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Increasing attention has focused on the contributions of persistent microbial infections with the manifestation of disease later in life, including neurodegenerative conditions such as Alzheimer’s disease (AD). Current data has shown the presence of herpes simplex virus 1 (HSV-1) in regions of the brain that are impacted by AD in elderly individuals. Additionally, neuronal infection with HSV-1 triggers the accumulation of amyloid beta deposits and hyperphosphorylated tau, and results in oxidative stress and synaptic dysfunction. All of these factors are implicated in the development of AD. These data highlight the fact that persistent viral infection is likely a contributing factor, rather than a sole cause of disease. Details of the correlations between HSV-1 infection and AD development are still just beginning to emerge. Future research should investigate the relative impacts of virus strain- and host-specific factors on the induction of neurodegenerative processes over time, using models such as infected neurons in vitro, and animal models in vivo, to begin to understand their relationship with cognitive dysfunction.

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Section: Strain-specific Differences In Hsv-1 Neurovirulence and Tmentioning

confidence: 99%

Persistent Infection with Herpes Simplex Virus 1 and Alzheimer’s Disease—A Call to Study How Variability in Both Virus and Host may Impact Disease

Mangold

Szpara

2019

Viruses

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“…El aumento de la frecuencia de estos reportes sugiere, en primera instancia, que se han producido cambios en el perfil de la enfermedad debidos, probablemente, a variaciones en el tropismo del virus que promueven su interacción con diferentes tipos de moléculas y células receptoras. Ello resalta la necesidad de conocer más sobre el virus y sobre los posibles mecanismos a los que recurre para infectar diferentes tipos de células y tejidos (29,30).…”

Section: Discussionunclassified

“…Para infectar ratones se requiere de la modificación de factores virales, del huésped o de ambos. Cuando esto se ha logrado, se ha detectado que las neuronas son el principal sitio de replicación viral en el sistema nervioso (30,32).…”

Section: Discussionunclassified

La infección con el virus del dengue induce apoptosis en células del neuroblastoma humano SH-SY5Y

2016

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Contribución de los autores:Jaime E. Castellanos: ejecución del proyecto, análisis e interpretación de datos José I. Neissa: aplicación de la metodología Sigrid J. Camacho: análisis e interpretación de datos Todos los autores participaron en la redacción del manuscrito. Introducción. El dengue es una enfermedad humana producida por el virus del mismo nombre, que se transmite por la picadura de mosquitos del género Aedes. La infección tiene una amplia gama de presentaciones clínicas que van desde la ausencia de síntomas hasta los casos fatales y afecta principalmente a la población pediátrica. Según la nueva clasificación de la enfermedad, las manifestaciones neurológicas se consideran un criterio para el diagnóstico del dengue grave. Objetivo. Evaluar los posibles mecanismos involucrados en la aparición de los signos neurológicos en una línea celular de neuronas humanas, como modelo de infección con el virus del dengue del serotipo 2 (DENV-2). Materiales y métodos. Se evaluó la sensibilidad y la permisividad de la línea celular SH-SY5Y a la infección por el DENV-2; se encontró que la proporción entre infección y producción viral era similar a las de las células de primates usadas como control positivo de la infección. La infección con el virus del dengue induce apoptosis en células del neuroblastoma humano SH-SY5YResultados. La infección indujo un efecto citopático en la línea celular de neuroblastoma caracterizado por un proceso de muerte apoptótica, con aumento en la proporción de células positivas al emplear los métodos de anexina V y TUNEL. Se encontró una regulación positiva del factor de necrosis tumoral alfa (TNF-α), y el tratamiento con un anticuerpo anti-TNF-α aumentó ligeramente la supervivencia de las células infectadas. La adición de TNF-α exógeno a los cultivos infectados potenció la muerte celular. Conclusión. Estos resultados sugieren, en su conjunto, que la regulación positiva del TNF-α podría hacer parte del proceso que induce daño y muerte celular durante el desarrollo de la encefalitis por dengue.Palabras clave: dengue, apoptosis, factor de necrosis tumoral alfa, supervivencia celular, manifestaciones neurológicas, encefalitis. doi: http://dx.doi.org/10.7705/biomedica.v36i0.2984 Dengue virus induces apoptosis in SH-SY5Y human neuroblastoma cellsIntroduction: Dengue is a human disease caused by a virus with the same name, which is transmitted by the bite of Aedes mosquitoes. The infection has a wide range of clinical presentations ranging from asymptomatic to fatal cases, with the pediatric population being the most susceptible. According to the new classification of the disease, the neurological manifestations are considered a criterion for the diagnosis of severe dengue. Conclusion:These results as a whole suggest that the upregulation of TNF-α could be part of the process that induces cell damage and death in cases of dengue encephalitis.

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“…Arbovirus-associated neurological diseases may be caused by the direct action of viruses, inflammatory reaction in nervous tissue or systemic metabolic alterations (encephalopathies), induced or not by the exacerbated systemic immune response (17). Neurological manifestations are consequence of virus-host complex interactions, including the viral neuroinvasive, neurotropic and neurovirulent properties and host susceptibility and host immune response (17,18). Flaviviruses entry in cells by endocytosis after the binding of the viral envelop glycoprotein to the carbohydrate target-cell receptors (DC-SIGN and others), and by phagocytosis of the antibody-virus complex (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

“…Neurological manifestations are consequence of virus-host complex interactions, including the viral neuroinvasive, neurotropic and neurovirulent properties and host susceptibility and host immune response (17,18). Flaviviruses entry in cells by endocytosis after the binding of the viral envelop glycoprotein to the carbohydrate target-cell receptors (DC-SIGN and others), and by phagocytosis of the antibody-virus complex (17)(18)(19). Viruses penetrate the nervous system by different mechanisms, including the passage of the free-virus or infected immune cells through the hematogenous pathway across the blood-brain-barrier (BBB), direct infection of brain endothelial cells or transport of virus captured by peripheral sensory neural fibers by retrograde axonal pathway (20,21).…”

Section: Introductionmentioning

confidence: 99%

Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications

et al. 2021

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Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1β, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.

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Flavivirus Neurotropism, Neuroinvasion, Neurovirulence and Neurosusceptibility: Clues to Understanding Flavivirus- and Dengue-Induced Encephalitis

Cited by 6 publications

References 116 publications

Persistent Infection with Herpes Simplex Virus 1 and Alzheimer’s Disease—A Call to Study How Variability in Both Virus and Host may Impact Disease

Persistent Infection with Herpes Simplex Virus 1 and Alzheimer’s Disease—A Call to Study How Variability in Both Virus and Host may Impact Disease

La infección con el virus del dengue induce apoptosis en células del neuroblastoma humano SH-SY5Y

Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications

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