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1.
Microb Pathog ; 196: 106917, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39243991

RESUMEN

This report aims to describe the identification of porcine astrovirus 3 (PAstV3) RNA in the central nervous system (CNS) of weaned pigs with clinical signs of neurological disease associated with polioencephalomyelitis in southeastern Brazil. Three, 20 -35 days-old piglets that died after clinical manifestations of a neurological syndrome were submitted to post-mortem evaluations. Tissue samples were examined by histopathology, bacteriology, and molecular assays (RT-PCR, nested-PCR, RT-qPCR, and Sanger sequencing) to detect the primary infectious disease agents associated with neurological disease in pigs. The principal neuropathological alterations occurred in the grey matter of the spinal cord and brainstem resulting in nonsuppurative poliomyelitis and rhombencephalitis. PAstV3 RNA was detected in the CNS samples of all piglets with histopathological evidence of disease and was confirmed by nucleotide sequencing. Nucleic acids from pathogens commonly associated with neurological diseases in pigs, such as porcine teschovirus, porcine sapelovirus, porcine enterovirus G, atypical porcine pestivirus, senecavirus A, and encephalomyocarditis virus was not detected by molecular assays in the three piglets. This is the first report of PAstV3 in piglets with neurological disease and lesions consistent with polioencephalomyelitis in Brazil. This report highlights the importance of monitoring health events that could compromise pig farming productivity and animal welfare.


Asunto(s)
Encefalomielitis , Mamastrovirus , ARN Viral , Enfermedades de los Porcinos , Animales , Porcinos , Brasil , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/patología , ARN Viral/genética , Mamastrovirus/aislamiento & purificación , Mamastrovirus/genética , Encefalomielitis/veterinaria , Encefalomielitis/virología , Encefalomielitis/patología , Infecciones por Astroviridae/veterinaria , Infecciones por Astroviridae/virología , Infecciones por Astroviridae/patología , Filogenia , Sistema Nervioso Central/virología , Sistema Nervioso Central/patología , Médula Espinal/patología , Médula Espinal/virología
2.
Commun Biol ; 7(1): 811, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965360

RESUMEN

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.


Asunto(s)
Encéfalo , Senescencia Celular , Herpes Simple , Herpesvirus Humano 1 , Esclerosis Múltiple , Animales , Ratones , Encéfalo/virología , Encéfalo/patología , Encéfalo/metabolismo , Esclerosis Múltiple/virología , Esclerosis Múltiple/patología , Esclerosis Múltiple/metabolismo , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 1/patogenicidad , Herpes Simple/virología , Herpes Simple/patología , Femenino , Ratones Endogámicos C57BL , Encefalomielitis Autoinmune Experimental/virología , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Fenotipo , Sistema Nervioso Central/virología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Médula Espinal/virología , Médula Espinal/metabolismo , Médula Espinal/patología , Biomarcadores/metabolismo , Encefalitis por Herpes Simple/virología , Encefalitis por Herpes Simple/patología , Encefalitis por Herpes Simple/metabolismo
3.
Bol. méd. postgrado ; 37(1): 15-20, Ene-Jun 2021. ilus
Artículo en Español | LILACS, LIVECS | ID: biblio-1147873

RESUMEN

Se desarrollan los principales elementos históricos en el estudio y la lucha contra la poliomielitis, su aislamiento por Karl Landsteiner en 1909, la primera vacuna con virus muerto (Jonas Salk, 1955), la segunda vacuna con virus vivo atenuado (Albert Sabin, 1961) y la reducción paulatina de la polio en todo el mundo, hasta llegar a menos de 200 casos al año (virus salvaje)(AU)


The main historical events in the study and fight against polio are shown, its isolation by Karl Landsteiner in 1909, the development of the first vaccine with dead virus (Jonas Salk, 1955), the second vaccine with live attenuated virus (Albert Sabin, 1961) and the gradual reduction of polio worldwide, reaching less than 200 cases a year (wild virus)(AU)


Asunto(s)
Poliomielitis/mortalidad , Poliomielitis/virología , Enfermedades Virales del Sistema Nervioso Central , Poliovirus , Médula Espinal/virología , Vacuna Antipolio de Virus Inactivados , Vacuna Antipolio Oral
4.
Ann Clin Transl Neurol ; 7(10): 2072-2073, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32941703

RESUMEN

A 37 year-old previously healthy man from Jamaica presented with 2-3 months of progressive trouble ambulating and incontinence. By 1 month prior to arrival he was wheelchair bound and unable to ambulate even with assistance. He started to wear a diaper for bladder and bowel incontinence. He also complained of painless numbness in his legs over the same period of time. His exam is notable for marked weakness and spasticity in his legs, with hyper-reflexia and clonus. He has a sensory level at the level of the umbilicus. An MRI shows a longitudinally extensive T2 signal change throughout the thoracic cord. His cerebrospinal fluid is mildly inflammatory. His HTLV-1 antibody test is reactive.


Asunto(s)
Anticuerpos Anti-HTLV-I/orina , Enfermedades del Sistema Nervioso/patología , Neoplasias de la Médula Espinal/fisiopatología , Incontinencia Urinaria/fisiopatología , Adulto , Humanos , Jamaica , Masculino , Enfermedades del Sistema Nervioso/fisiopatología , Médula Espinal/virología , Incontinencia Urinaria/diagnóstico
5.
Am J Trop Med Hyg ; 99(6): 1419-1421, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30277201

RESUMEN

We report here one case of Zika virus (ZIKV) infection associated with auto-immunity directed against the central nervous system in a Brazilian woman who developed acute transverse myelitis 9 days after recovery from an acute episode of fever with generalized erythema. Imaging of the spinal cord showed an elongated area on the T1-T10 level with gadolinium uptake. The diagnostic of the ZIKV infection was confirmed by cerebrospinal fluid and serum analysis. This patient had serum positivity for autoantibodies against myelin oligodendrocyte glycoprotein (MOG), a specific antibody against the myelin sheath. We propose that a direct central nervous system infection by ZIKV could lead to a specific auto-immunity against MOG protein.


Asunto(s)
Autoanticuerpos/biosíntesis , Eritema/inmunología , Mielitis Transversa/inmunología , Médula Espinal/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/patogenicidad , Enfermedad Aguda , Adulto , Brasil , Medios de Contraste/administración & dosificación , Eritema/complicaciones , Eritema/diagnóstico por imagen , Eritema/virología , Femenino , Gadolinio/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Vaina de Mielina/inmunología , Vaina de Mielina/patología , Vaina de Mielina/virología , Glicoproteína Mielina-Oligodendrócito/antagonistas & inhibidores , Glicoproteína Mielina-Oligodendrócito/inmunología , Mielitis Transversa/diagnóstico por imagen , Mielitis Transversa/etiología , Mielitis Transversa/virología , Médula Espinal/diagnóstico por imagen , Médula Espinal/virología , Virus Zika/fisiología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico por imagen , Infección por el Virus Zika/virología
6.
Biomedica ; 38(2): 209-215, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-30184349

RESUMEN

Introduction: Information about the neuroanatomical details of the ascendant transport of the rabies virus through the spinal cord is scarce. Objective: To identify the neuroanatomical route of dissemination of the rabies virus at each of the levels of the spinal cord of mice after being inoculated intramuscularly. Materials and methods: Mice were inoculated with the rabies virus in the hamstrings. After 24 hours post-inoculation, every eight hours, five animals were sacrificed by perfusion with paraformaldehyde. Then, the spinal cord was removed, and transverse cuts were made at the lumbosacral, thoracic, and cervical levels. These were processed by immunohistochemistry for the detection of viral antigens. Results: The first antigens of rabies were observed as aggregated particles in the lumbar spinal cord at 24 hours post-inoculation, within the ventral horn in the same side of the inoculated limb. At 32 hours post inoculation the first motoneurons immunoreactive to the virus became visible. At 40 hours postinoculation the first immunoreactive neurons were revealed in the thoracic level, located on lamina 8 and at 48 hours post-inoculation in the cervical cord, also on lamina 8. At 56 hours post-inoculation the virus had spread throughout the spinal cord, but the animals still did not show signs of the disease. Conclusion: In the mouse model we used, the rabies virus entered the spinal cord through the motoneurons and probably used the descending propriospinal pathway for its retrograde axonal transport to the encephalus.


Asunto(s)
Virus de la Rabia/fisiología , Médula Espinal/virología , Animales , Femenino , Ratones , Médula Espinal/anatomía & histología
7.
PLoS Negl Trop Dis ; 12(8): e0006720, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30148843

RESUMEN

BACKGROUND: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. METHODOLOGY: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). PRINCIPAL FINDINGS: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. CONCLUSIONS: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. SIGNIFICANCE: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.


Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/virología , Médula Espinal/metabolismo , Brasil/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Estudios Transversales , Humanos , Microcirculación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Médula Espinal/patología , Médula Espinal/virología , Carga Viral
8.
Biomédica (Bogotá) ; Biomédica (Bogotá);38(2): 209-215, ene.-jun. 2018. graf
Artículo en Español | LILACS | ID: biblio-950939

RESUMEN

Resumen Introducción. Es escasa la información sobre los detalles neuroanatómicos del transporte del virus de la rabia en su ascenso por la médula espinal. Objetivos. Identificar la ruta neuroanatómica de diseminación del virus de la rabia en cada uno de los niveles de la médula espinal de ratón, después de ser inoculado por vía intramuscular. Materiales y métodos. Se inocularon ratones en los músculos isquiotibiales, con virus de la rabia. A partir de las 24 horas después de la inoculación, cada ocho horas se sacrificaron cinco animales por perfusión con paraformaldehído, se les extrajo la médula espinal y se hicieron cortes transversales en los niveles lumbosacro, torácico y cervical. Estos se procesaron mediante inmunohistoquímica para detectar antígenos virales. Resultados. Los primeros antígenos de la rabia se observaron como partículas agregadas, en la médula espinal lumbar, a las 24 horas después de la inoculación, dentro del asta ventral ipsilateral a la extremidad inoculada. A las 32 horas después de la inoculación, se hicieron visibles las primeras motoneuronas inmunorreactivas al virus. A las 40 horas después de la inoculación, se revelaron las primeras neuronas inmunorreactivas en la médula torácica, localizadas en la lámina 8 y, a las 48 horas después de la inoculación en la médula cervical, también en la lámina 8. A las 56 horas después de la inoculación, el virus se había diseminado por toda la médula espinal pero los animales aún no revelaban signos de la enfermedad. Conclusión. En el modelo de ratón aquí utilizado, el virus de la rabia ingresó a la médula espinal por las motoneuronas y, probablemente, utilizó la vía propioespinal descendente para su transporte axonal retrógrado hasta el encéfalo.


Abstract Introduction: Information about the neuroanatomical details of the ascendant transport of the rabies virus through the spinal cord is scarce. Objective: To identify the neuroanatomical route of dissemination of the rabies virus at each of the levels of the spinal cord of mice after being inoculated intramuscularly. Materials and methods: Mice were inoculated with the rabies virus in the hamstrings. After 24 hours post-inoculation, every eight hours, five animals were sacrificed by perfusion with paraformaldehyde. Then, the spinal cord was removed, and transverse cuts were made at the lumbosacral, thoracic, and cervical levels. These were processed by immunohistochemistry for the detection of viral antigens. Results: The first antigens of rabies were observed as aggregated particles in the lumbar spinal cord at 24 hours post-inoculation, within the ventral horn in the same side of the inoculated limb. At 32 hours post inoculation the first motoneurons immunoreactive to the virus became visible. At 40 hours post-inoculation the first immunoreactive neurons were revealed in the thoracic level, located on lamina 8 and at 48 hours post-inoculation in the cervical cord, also on lamina 8. At 56 hours post-inoculation the virus had spread throughout the spinal cord, but the animals still did not show signs of the disease. Conclusion: In the mouse model we used, the rabies virus entered the spinal cord through the motoneurons and probably used the descending propriospinal pathway for its retrograde axonal transport to the encephalus.


Asunto(s)
Animales , Femenino , Ratones , Virus de la Rabia/fisiología , Médula Espinal/virología , Médula Espinal/anatomía & histología
9.
Viruses ; 10(3)2018 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-29509660

RESUMEN

Rabies is a viral infection that targets the nervous system, specifically neurons. The clinical manifestations of the disease are dramatic and their outcome fatal; paradoxically, conventional histopathological descriptions reveal only subtle changes in the affected nervous tissue. Some researchers have considered that the pathophysiology of rabies is based more on biochemical changes than on structural alterations, as is the case with some psychiatric diseases. However, we believe that it has been necessary to resort to other methods that allow us to analyze the effect of the infection on neurons. The Golgi technique is the gold standard for studying the morphology of all the components of a neuron and the cytoskeletal proteins are the structural support of dendrites and axons. We have previously shown, in the mouse cerebral cortex and now with this work in spinal cord, that rabies virus generates remarkable alterations in the morphological pattern of the neurons and that this effect is associated with the increase in the expression of two cytoskeletal proteins (MAP2 and NF-H). It is necessary to deepen the investigation of the pathogenesis of rabies in order to find therapeutic alternatives to a disease to which the World Health Organization classifies as a neglected disease.


Asunto(s)
Dendritas/genética , Dendritas/virología , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neurofilamentos/genética , Virus de la Rabia/fisiología , Rabia/genética , Rabia/virología , Médula Espinal/metabolismo , Médula Espinal/virología , Animales , Dendritas/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Inmunohistoquímica , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neuronas/metabolismo , Neuronas/patología , Neuronas/virología , Rabia/diagnóstico , Médula Espinal/patología
10.
BMJ Case Rep ; 20172017 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-28801328

RESUMEN

We report a case of transverse myelitis in an immunocompetent host with an atypical long onset of symptoms. A 56-year-old man was admitted to the hospital reporting 5 months of progressive ascending lower extremity weakness and numbness, inability to walk, bowel incontinence,urinary retention and several episodes of nausea and vomiting. MRI showed moderate spinal swelling and multiple hyperintense signal changes on cervical levels C2-C5 and thoracic levels T1-T3. Cerebrospinal fluid (CSF) showed pleocytosis and was positive for anti-cytomegalovirus (CMV) IgG intrathecal antibodies, but the CSF PCR for CMV was negative. The diagnosis of immune-mediated CMV-related transverse myelitis was established and the patient was treated with methylprednisolone and valgancyclovir. The patient had poor recovery and remained paraplegic at discharge.


Asunto(s)
Antiinflamatorios/uso terapéutico , Infecciones por Citomegalovirus/fisiopatología , Citomegalovirus/aislamiento & purificación , Ganciclovir/análogos & derivados , Metilprednisolona/uso terapéutico , Mielitis Transversa/fisiopatología , Paraplejía/virología , Médula Espinal/fisiopatología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , Progresión de la Enfermedad , Resultado Fatal , Ganciclovir/uso terapéutico , Humanos , Inmunocompetencia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielitis Transversa/tratamiento farmacológico , Mielitis Transversa/virología , Paraplejía/fisiopatología , Médula Espinal/virología , Valganciclovir
11.
Am J Trop Med Hyg ; 96(2): 380-381, 2017 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-27956656

RESUMEN

Dengue fever is the most common arbovirus disease, and presents with a large spectrum of clinical manifestations ranging from asymptomatic disease through to the development of dengue hemorrhagic fever. These extreme cases can lead to dengue shock syndrome, and sometimes death. Spinal cord involvement in dengue virus (DENV) infections is rare. Here, we report a case in which the patient developed acute transverse myelitis (TM) without paraparesis following a DENV infection. This case highlights the importance of physicians' awareness of the possible link between DENV and TM in endemic areas.


Asunto(s)
Dengue/complicaciones , Mielitis Transversa/etiología , Brasil , Humanos , Imagen por Resonancia Magnética , Masculino , Mielitis Transversa/diagnóstico por imagen , Mielitis Transversa/virología , Médula Espinal/diagnóstico por imagen , Médula Espinal/virología , Adulto Joven
12.
J Neurovirol ; 22(1): 125-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26306687

RESUMEN

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.


Asunto(s)
Fiebre Chikungunya/diagnóstico , Neuralgia/diagnóstico , Radiculopatía/diagnóstico , Enfermedades de la Médula Espinal/diagnóstico , Corticoesteroides/uso terapéutico , Fiebre Chikungunya/complicaciones , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/fisiopatología , Virus Chikungunya/patogenicidad , Virus Chikungunya/fisiología , República Dominicana , Femenino , Humanos , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Neuralgia/complicaciones , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Radiculopatía/complicaciones , Radiculopatía/tratamiento farmacológico , Radiculopatía/fisiopatología , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Médula Espinal/virología , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/tratamiento farmacológico , Enfermedades de la Médula Espinal/fisiopatología , Viaje , Estados Unidos
13.
Viruses ; 6(10): 3827-36, 2014 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-25310583

RESUMEN

Oropouche virus (OROV) is an important cause of arboviral illness in Brazil and other Latin American countries, with most cases clinically manifested as acute febrile illness referred to as Oropouche fever, including myalgia, headache, arthralgia and malaise. However, OROV can also affect the central nervous system (CNS) with clinical neurological implications. Little is known regarding OROV pathogenesis, especially how OROV gains access to the CNS. In the present study, neonatal BALB/c mice were inoculated with OROV by the subcutaneous route and the progression of OROV spread into the CNS was evaluated. Immunohistochemistry revealed that OROV infection advances from posterior parts of the brain, including the periaqueductal gray, toward the forebrain. In the early phases of the infection OROV gains access to neural routes, reaching the spinal cord and ascending to the brain through brainstem regions, with little inflammation. Later, as infection progresses, OROV crosses the blood-brain barrier, resulting in more intense spread into the brain parenchyma, with more severe manifestations of encephalitis.


Asunto(s)
Infecciones por Bunyaviridae/virología , Sistema Nervioso Central/virología , Orthobunyavirus/fisiología , Animales , Animales Recién Nacidos , Antígenos Virales/análisis , Tronco Encefálico/patología , Tronco Encefálico/virología , Infecciones por Bunyaviridae/patología , Ratones , Ratones Endogámicos BALB C , Orthobunyavirus/inmunología , Médula Espinal/patología , Médula Espinal/virología
14.
Virus Res ; 170(1-2): 25-33, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22877689

RESUMEN

Oropouche virus, of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil. An estimated 500,000 cases of Oropouche fever have occurred in Brazil in the last 30 years, with recorded cases also in Panama, Peru, Suriname and Trinidad. We have developed an experimental model of Oropouche virus infection in neonatal BALB/c mouse by subcutaneous inoculation. The vast majority of infected animals developed disease on the 5th day post infection, characterized mainly by lethargy and paralysis, progressing to death within 10 days. Viral replication was documented in brain cells by in situ hybridization, immunohistochemistry and virus titration. Multi-step immunohistochemistry indicated neurons as the main target cells of OROV infection. Histopathology revealed glial reaction and astrocyte activation in the brain and spinal cord, with neuronal apoptosis. Spleen hyperplasia and mild meningitis were also found, without viable virus detected in liver and spleen. This is the first report of an experimental mouse model of OROV infection, with severe involvement of the central nervous system, and should become useful in pathogenesis studies, as well as in preclinical testing of therapeutic interventions for this emerging pathogen.


Asunto(s)
Infecciones por Bunyaviridae/virología , Virus Simbu/patogenicidad , Animales , Apoptosis , Encéfalo/patología , Encéfalo/virología , Infecciones por Bunyaviridae/mortalidad , Infecciones por Bunyaviridae/patología , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos BALB C , Neuronas/patología , Médula Espinal/patología , Médula Espinal/virología , Carga Viral , Pérdida de Peso
15.
Arq Neuropsiquiatr ; 70(4): 246-51, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22510735

RESUMEN

OBJECTIVE: To investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (CSF) findings in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: We studied brain and cervical spinal cord on magnetic resonance imaging (MRI) and CSF examinations of 28 Brazilian HAM/TSP patients. RESULTS: The majority of patients had severe neurological incapacity with EDSS median of 6.5 (3-8). The brain MRI showed white matter lesions (75%) and atrophy (14%). The preferential brain location was periventricular. Cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. One patient had enhancement lesions on T1 cervical spinal cord MRI. Cases with spinal cord lesions had signs of acute CSF inflammation. The brain white matter lesions predominated in the patients with higher age. CONCLUSION: Our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in HAM/TSP. The brain abnormalities are not related to the clinical picture of HAM/TSP.


Asunto(s)
Encéfalo/patología , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Paraparesia Espástica Tropical/patología , Adulto , Anciano , Atrofia/líquido cefalorraquídeo , Atrofia/patología , Encéfalo/virología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Médula Espinal/patología , Médula Espinal/virología
16.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;70(4): 246-251, Apr. 2012. ilus, tab
Artículo en Inglés | LILACS | ID: lil-622586

RESUMEN

OBJECTIVE: To investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (CSF) findings in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: We studied brain and cervical spinal cord on magnetic resonance imaging (MRI) and CSF examinations of 28 Brazilian HAM/TSP patients. RESULTS: The majority of patients had severe neurological incapacity with EDSS median of 6.5 (3-8). The brain MRI showed white matter lesions (75%) and atrophy (14%). The preferential brain location was periventricular. Cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. One patient had enhancement lesions on T1 cervical spinal cord MRI. Cases with spinal cord lesions had signs of acute CSF inflammation. The brain white matter lesions predominated in the patients with higher age. CONCLUSION: Our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in HAM/TSP. The brain abnormalities are not related to the clinical picture of HAM/TSP.


OBJETIVO: Analisar a associação entre aspectos clínicos, lesões de substância branca e reação inflamatória aguda no líquido cefalorraquidiano (LCR) na mielopatia associa ao HTLV-1 (HAM/TSP). MÉTODO: Foram estudadas ressonâncias magnéticas (RM) do encéfalo/medula espinhal cervical e exame do LCR de 28 pacientes com HAM/TSP. RESULTADOS: A maioria dos pacientes apresentava grave incapacidade neurológica, com EDSS 6,5 (3-8). A RM revelou lesões da substância branca (75%) com predominância periventricular e atrofia cortical (14%). Lesões desmielinizantes cervicais ocorreram em 11% dos casos e atrofia em 3,5%. Um paciente apresentou lesão cervical na T1 com captação de contraste. Sinais de inflamação aguda no LCR ocorreram em situações de lesão da medula espinhal cervical. As alterações de substância branca do encéfalo predominaram nos indivíduos com maior faixa etária. CONCLUSÃO: Nossos achados sugerem que processo inflamatório com atividade clínica na HAM/TSP está associado a lesões da medula espinhal cervical. As anormalidades da substância branca encefálicas não são relacionadas ao quadro clínico de HAM/TSP.


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encéfalo/patología , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Paraparesia Espástica Tropical/patología , Atrofia/líquido cefalorraquídeo , Atrofia/patología , Encéfalo/virología , Imagen por Resonancia Magnética , Estudios Prospectivos , Médula Espinal/patología , Médula Espinal/virología
17.
Neurol India ; 59(1): 114-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21339677

RESUMEN

The most frequent neurologic manifestations of hepatitis C virus infection include peripheral neuropathy axonal type and central nervous system (CNS) vasculitis. Affected patients usually have cryoglobulinemia and other signs of vasculitis. Demyelinating lesions, both central and peripheral are rarely described. We present a case of simultaneous peripheral nervous system and CNS demyelination that comes in relapsing episodes, with negative cryoglobulins.


Asunto(s)
Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/virología , Hepatitis C/complicaciones , Enfermedades del Sistema Nervioso Periférico , Adolescente , Encéfalo/patología , Encéfalo/virología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/virología , Médula Espinal/patología , Médula Espinal/virología
18.
Microb Pathog ; 48(2): 69-73, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19931373

RESUMEN

Bovine herpetic mammillits is a self-limiting cutaneous disease of the udder and teats of cows associated with bovine herpesvirus 2 (BoHV-2) whose pathogenesis is poorly understood. This article describes the use of guinea pigs (Cavia porcellus) to study the pathogenesis of BoHV-2 infection. Twelve weanling female guinea pigs inoculated subcutaneously with BoHV-2 in the genitalia and teats developed local hyperemia, edema, vesicles, ulcers and scabs. Infectious virus was recovered between days 3 and 7 post-infection (pi) from the genital area (9/12) and teats (1/12); and all inoculated animals seroconverted (virus-neutralizing titers of 16-128). Histological examination of lesions revealed lymphoplasmacytic perivascular infiltrates and intranuclear inclusion bodies in keratinocytes. PCR examination of tissues collected at day 35 pi detected latent viral DNA predominantly in lumbosacral spinal segments. In another experiment, eight females inoculated with BoHV-2 in the genitalia and treated with dexamethasone (Dx) at day 35 pi developed mild to moderate local signs, yet no virus could be recovered from lesions. PCR examination of spinal segments from these animals confirmed the presence of latent viral DNA. These results demonstrate that guinea pigs are susceptible to BoHV-2 infection and therefore may be used to study selected aspects of BoHV-2 biology.


Asunto(s)
Modelos Animales de Enfermedad , Cobayas , Herpes Simple/veterinaria , Herpesvirus Bovino 2 , Latencia del Virus , Enfermedad Aguda , Animales , Anticuerpos Antivirales/sangre , Bovinos , Enfermedades de los Bovinos/virología , ADN Viral/análisis , Dexametasona/farmacología , Femenino , Genitales Femeninos/virología , Herpes Simple/patología , Herpes Simple/virología , Herpesvirus Bovino 2/genética , Herpesvirus Bovino 2/inmunología , Herpesvirus Bovino 2/aislamiento & purificación , Herpesvirus Bovino 2/fisiología , Glándulas Mamarias Animales/virología , Pruebas de Neutralización , Reacción en Cadena de la Polimerasa , Médula Espinal/virología , Proteínas del Envoltorio Viral/inmunología , Activación Viral , Replicación Viral
19.
Cent Nerv Syst Agents Med Chem ; 9(2): 137-49, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20021347

RESUMEN

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic progressive myelopathy characterized by bilateral pyramidal tracts involvement with sphincteric disturbances. HTLV-I infects approximately 10-20 million people worldwide. There are large endemic areas in southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. Since the primary neuropathological feature of HAM/TSP is chronic inflammation caused by HTLV-I infection in the spinal cord, various treatments focusing on immunomodulatory or anti-viral effects were performed for HAM/TSP patients until now. However, there are still many of problems, such as insufficient effects, side effects and expensive costs in long-term treatments, etc., in these treatments. Therefore, an ideal therapeutic strategy against HAM/TSP is still not established yet. Although only a small proportion of HTLV-I-infected individuals develops HAM/TSP, neurological symptoms are certainly progressive once myelopathy develops, leading to deterioration of the quality of life. Therefore, we now need the therapeutic regimens to protect the development, or be able to commence the treatments as soon as possible after the development safely and inexpensively even in long-term course or lifelong course of treatment. As HTLV-I-infected CD4(+) T cells are the first responders in the immunopathogenesis of HAM/TSP, the ideal treatment is the elimination of HTLV-I-infected cells from the peripheral blood. In this article, we will review the therapeutic strategies against HAM/TSP up to now and will introduce our new therapeutic approach focusing on the targeting of HTLV-I-infected cells in HAM/TSP patients.


Asunto(s)
ADN Viral/análisis , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Interferón gamma/uso terapéutico , Paraparesia Espástica Tropical/tratamiento farmacológico , África , Líquido del Lavado Bronquioalveolar , Región del Caribe , Portador Sano/tratamiento farmacológico , Portador Sano/virología , Recuento de Células , Línea Celular , Diagnóstico Diferencial , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/tratamiento farmacológico , Virus Linfotrópico T Tipo 1 Humano/efectos de los fármacos , Humanos , Japón , Leucocitos Mononucleares/virología , Medio Oriente , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/virología , América del Sur , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Médula Espinal/virología , Enfermedades de la Médula Espinal/tratamiento farmacológico , Células TH1/virología
20.
Vet Immunol Immunopathol ; 124(3-4): 264-73, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18490062

RESUMEN

Pseudorabies virus (PRV) is an alphaherpesvirus that causes a neurological disease in many wild and domestic animals. The neuropathology elicited by PRV is quite consistent regardless of the host with the only exception of mink, in which it is characterized by a vasculopathy rather than by an encephalitis. In this study, we aimed to investigate the underlying pathogenic mechanism(s) of PRV infection in mink by using immunohistochemistry and laser capture microdissection (LCM) on material from naturally and experimentally infected animals. The inflammatory reaction induced by PRV was minimal or absent not only in the nervous system, where we identified a low number of macrophages and a few T lymphocytes, but also in the primary replication site, the oropharyngeal mucosa; however, the number of PRV-infected cells detected by immunohistochemistry was extremely high both in the peripheral mucosa and in the nervous tissue. On the other hand, the vascular pathology included parenchymal hemorrhages of various degrees and, in specific cortical areas of the brain, fibrinoid degeneration of the capillary walls. Detection of viral antigens by immunohistochemistry revealed infection of endothelial cells of capillaries situated both in the oropharyngeal mucosa and in the brain stem; the presence of PRV DNA in vessels was further demonstrated by PCR performed on LCM samples of brain capillaries. These results can be interpreted as supporting the idea that the different pathology of the disease in mink may be the consequence of an increased endotheliotropism of PRV in this species. Infection of the vessel wall may then lead to vascular pathology and impairment in endothelial cell function, resulting in a weak immune response to infection.


Asunto(s)
Enfermedades del Sistema Nervioso Central/veterinaria , Herpesvirus Suido 1/patogenicidad , Visón/virología , Seudorrabia/virología , Animales , Encéfalo/inmunología , Encéfalo/patología , Encéfalo/virología , Enfermedades del Sistema Nervioso Central/inmunología , Enfermedades del Sistema Nervioso Central/patología , Enfermedades del Sistema Nervioso Central/virología , ADN Viral/química , ADN Viral/genética , Femenino , Herpesvirus Suido 1/inmunología , Inmunohistoquímica/veterinaria , Masculino , Visón/inmunología , Reacción en Cadena de la Polimerasa/veterinaria , Seudorrabia/inmunología , Seudorrabia/patología , Médula Espinal/inmunología , Médula Espinal/patología , Médula Espinal/virología
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