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1.
J Neurovirol ; 27(3): 452-462, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33876413

RESUMEN

Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.


Asunto(s)
Quimiocina CCL7/genética , Quimiocina CXCL12/genética , Encefalitis Transmitida por Garrapatas/genética , Macrófagos/virología , Meningoencefalitis/genética , Monocitos/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/virología , Estudios de Casos y Controles , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/virología , Quimiocina CCL20/sangre , Quimiocina CCL20/líquido cefalorraquídeo , Quimiocina CCL20/genética , Quimiocina CCL7/sangre , Quimiocina CCL7/líquido cefalorraquídeo , Quimiocina CXCL12/sangre , Quimiocina CXCL12/líquido cefalorraquídeo , Quimiotaxis/inmunología , Encefalitis Transmitida por Garrapatas/sangre , Encefalitis Transmitida por Garrapatas/líquido cefalorraquídeo , Encefalitis Transmitida por Garrapatas/virología , Femenino , Regulación de la Expresión Génica , Humanos , Macrófagos/inmunología , Masculino , Meningoencefalitis/sangre , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/virología , Persona de Mediana Edad , Monocitos/inmunología , Estudios Retrospectivos
2.
J Neurovirol ; 27(1): 12-25, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33367960

RESUMEN

With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.


Asunto(s)
COVID-19/fisiopatología , Tos/fisiopatología , Fatiga/fisiopatología , Fiebre/fisiopatología , Meningoencefalitis/fisiopatología , SARS-CoV-2/patogenicidad , Adulto , Anciano , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , COVID-19/diagnóstico por imagen , COVID-19/virología , Confusión/diagnóstico por imagen , Confusión/tratamiento farmacológico , Confusión/fisiopatología , Confusión/virología , Tos/diagnóstico por imagen , Tos/tratamiento farmacológico , Tos/virología , Disnea/diagnóstico por imagen , Disnea/tratamiento farmacológico , Disnea/fisiopatología , Disnea/virología , Electroencefalografía , Fatiga/diagnóstico por imagen , Fatiga/tratamiento farmacológico , Fatiga/virología , Femenino , Fiebre/diagnóstico por imagen , Fiebre/tratamiento farmacológico , Fiebre/virología , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Meningoencefalitis/diagnóstico por imagen , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/virología , Persona de Mediana Edad , Neuroimagen , SARS-CoV-2/efectos de los fármacos , Tratamiento Farmacológico de COVID-19
3.
Eur J Clin Microbiol Infect Dis ; 40(8): 1645-1656, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33686558

RESUMEN

We investigated the incidence, clinical characteristics, risk factors, and outcome of meningoencephalitis (ME) in patients with COVID-19 attending emergency departments (ED), before hospitalization. We retrospectively reviewed all COVID patients diagnosed with ME in 61 Spanish EDs (20% of Spanish EDs, COVID-ME) during the COVID pandemic. We formed two control groups: non-COVID patients with ME (non-COVID-ME) and COVID patients without ME (COVID-non-ME). Unadjusted comparisons between cases and controls were performed regarding 57 baseline and clinical characteristics and 4 outcomes. Cerebrospinal fluid (CSF) biochemical and serologic findings of COVID-ME and non-COVID-ME were also investigated. We identified 29 ME in 71,904 patients with COVID-19 attending EDs (0.40‰, 95%CI=0.27-0.58). This incidence was higher than that observed in non-COVID patients (150/1,358,134, 0.11‰, 95%CI=0.09-0.13; OR=3.65, 95%CI=2.45-5.44). With respect to non-COVID-ME, COVID-ME more frequently had dyspnea and chest X-ray abnormalities, and neck stiffness was less frequent (OR=0.3, 95%CI=0.1-0.9). In 69.0% of COVID-ME, CSF cells were predominantly lymphocytes, and SARS-CoV-2 antigen was detected by RT-PCR in 1 patient. The clinical characteristics associated with a higher risk of presenting ME in COVID patients were vomiting (OR=3.7, 95%CI=1.4-10.2), headache (OR=24.7, 95%CI=10.2-60.1), and altered mental status (OR=12.9, 95%CI=6.6-25.0). COVID-ME patients had a higher in-hospital mortality than non-COVID-ME patients (OR=2.26; 95%CI=1.04-4.48), and a higher need for hospitalization (OR=8.02; 95%CI=1.19-66.7) and intensive care admission (OR=5.89; 95%CI=3.12-11.14) than COVID-non-ME patients. ME is an unusual form of COVID presentation (<0.5‰ cases), but is more than 4-fold more frequent than in non-COVID patients attending the ED. As the majority of these MEs had lymphocytic predominance and in one patient SARS-CoV-2 antigen was detected in CSF, SARS-CoV-2 could be the cause of most of the cases observed. COVID-ME patients had a higher unadjusted in-hospital mortality than non-COVID-ME patients.


Asunto(s)
COVID-19/complicaciones , Meningoencefalitis/virología , Adulto , Anciano , Cuidados Críticos , Servicio de Urgencia en Hospital , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , España
4.
J Infect Dis ; 222(4): 681-689, 2020 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-32201899

RESUMEN

BACKGROUND: Parechovirus (PeV)-A3 and enteroviruses (EV) are the most common viruses causing sepsis and meningoencephalitis in neonates and young infants. Clinical manifestations of PeV-A3 infection are more severe than those of EV infection, and no pleocytosis with a positive polymerase chain reaction (PCR) result for PeV-A3 in cerebrospinal fluid (CSF) are characteristic findings. We hypothesized that innate immune responses to PeV-A3 and EV are distinct in serum and CSF. METHODS: We evaluated 22 cytokines/chemokines in serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan, from 2015 through 2018. Infection was diagnosed with real-time PCR followed by sequencing. Febrile neonates and infants with sepsis-like syndrome who had negative bacterial culture and viral PCR for both PeV-A and EV were also included (non-PeV-A/EV patients). RESULTS: Among 192 febrile patients, we evaluated 16 PeV-A3-infected, 15 EV-infected, and 8 non-PeV-A/EV patients. Serum pro-/anti-inflammatory cytokine/chemokine levels were higher in PeV-A3-infected patients than in EV-infected patients (P < .02). Although most cytokine/chemokine were elevated in CSF from EV-infected patients, levels were low or undetectable in PeV-A3-infected and non-PeV-A/EV patients (P < .001). CONCLUSIONS: Distinct cytokine/chemokine patterns in serum and CSF may explain the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants.


Asunto(s)
Citocinas/metabolismo , Infecciones por Enterovirus/diagnóstico , Enterovirus/inmunología , Parechovirus/inmunología , Infecciones por Picornaviridae/diagnóstico , Líquido Cefalorraquídeo/virología , Enterovirus/genética , Infecciones por Enterovirus/fisiopatología , Femenino , Fiebre/etiología , Humanos , Inmunidad Innata , Lactante , Recién Nacido , Japón , Masculino , Meningoencefalitis/virología , Parechovirus/genética , Infecciones por Picornaviridae/fisiopatología , Sepsis/virología , Suero/virología
5.
J Gen Virol ; 101(3): 290-298, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31935178

RESUMEN

Bovine herpesvirus 5 (BoHV-5) is a pathogen of cattle responsible for fatal meningoencephalitis. Like alpha herpesvirus subfamily members, BoHV-5 also encodes microRNA in lytic infections of epithelial cells. BoHV-5-miR-B10 was the most abundant miRNA detected in a high-throughput sequencing study. Here, we evaluated the kinetics of miR-B10 expression after BoHV-5 productive infection by stem-loop real-time quantitative PCR. miR-B10 candidate target sites in the virus were predicted, and BoHV-5 UL39 was confirmed as a target gene by dual-luciferase assay with the design of an miR-B10 tough decoy (TuD). The UL39 gene encoding ribonucleotide reductase (RR) large subunit plays an important role in the early stage of BoHV-5 lytic infection. As BoHV-5-miR-B10 is located in internal and terminal repeat regions, we generated a TuD gene-integrated BoHV-5 strain, which effectively down-regulated miR-B10-3p. Strikingly, the suppression of miR-B10-3p significantly improved BoHV-5 replication. Taking these findings together, our study established an efficient method to deliver and express TuD RNA for viral miRNA suppression, and demonstrated that virus-encoded miRNA suppresses viral-genome biogenesis with a feedback mode, which might serve as a brake for viral replication. Herpesviruses infect humans and a variety of animals. Almost all herpesviruses can encode miRNAs, but the functions of these miRNAs remain to be elucidated. Most herpesvirus-encoded miRNA harbours dual copies, which is difficult to be deleted by current genetic modulation. Here, we developed an efficient method to deliver and express TuD RNA to efficiently suppress viral miRNA with multiple copies. Using this method, we demonstrated for the first time that viral miRNA feedback regulates viral replication by suppressing the expression of RR.


Asunto(s)
Enfermedades de los Bovinos/virología , Encefalitis Viral/virología , Retroalimentación Fisiológica , Infecciones por Herpesviridae/virología , Herpesvirus Bovino 5/genética , Meningoencefalitis/virología , MicroARNs/metabolismo , Replicación Viral/genética , Animales , Bovinos , Regulación Viral de la Expresión Génica , Células HEK293 , Humanos , MicroARNs/genética , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
6.
J Neurovirol ; 26(1): 14-22, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31529280

RESUMEN

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.


Asunto(s)
Infecciones por Enterovirus , Meningoencefalitis/virología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos
7.
J Neurovirol ; 26(4): 565-571, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32524423

RESUMEN

The aim of our study was to compare the course of TBE in children and adults. A retrospective analysis of the medical records of 669 patients was performed. The patients were categorized into 2 groups: Group I with 68 children and group II with 601 adults. TBE symptoms in children were milder compared with adults, with meningitis in 97% of cases. In adults, meningoencephalitis and meningoencephalomyelitis made up 49.26% of cases. Nausea and vomiting are more frequent in children, while neurological manifestations are more frequent in adults. There were no differences in CSF pleocytosis at the onset of disease in both groups, while CSF protein concentration was higher in adults. Children treated with corticosteroids over 7 days had higher checkup pleocytosis than pleocytosis at the onset of disease compared with adults. Corticosteroid use prolongs the disease duration but does not influence the development of TBE sequelae. Children had more favourable outcomes than adult patients.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas/patogenicidad , Encefalitis Transmitida por Garrapatas/patología , Encefalitis Viral/patología , Leucocitosis/patología , Meningitis Viral/patología , Meningoencefalitis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Niño , Preescolar , Dexametasona/uso terapéutico , Virus de la Encefalitis Transmitidos por Garrapatas/fisiología , Encefalitis Transmitida por Garrapatas/diagnóstico , Encefalitis Transmitida por Garrapatas/tratamiento farmacológico , Encefalitis Transmitida por Garrapatas/virología , Encefalitis Viral/diagnóstico , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Femenino , Humanos , Leucocitosis/diagnóstico , Leucocitosis/tratamiento farmacológico , Leucocitosis/virología , Masculino , Manitol/uso terapéutico , Meningitis Viral/diagnóstico , Meningitis Viral/tratamiento farmacológico , Meningitis Viral/virología , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/virología , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
8.
BMC Infect Dis ; 20(1): 886, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33238935

RESUMEN

BACKGROUND: To investigate the clinical characteristics of Epstein-Barr virus (EBV) infection in the pediatric nervous system (NS). METHODS: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019. RESULTS: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0-4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain-Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. CONCLUSION: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.


Asunto(s)
Encefalitis Viral/virología , Encefalomielitis Aguda Diseminada/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Síndrome de Guillain-Barré/virología , Herpesvirus Humano 4/inmunología , Linfohistiocitosis Hemofagocítica/virología , Trastornos Linfoproliferativos/virología , Meningoencefalitis/virología , Mielitis/virología , Adolescente , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/líquido cefalorraquídeo , Infecciones por Virus de Epstein-Barr/fisiopatología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Fiebre , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Pronóstico , Estudios Retrospectivos
9.
Int J Neurosci ; 130(3): 276-278, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31554442

RESUMEN

Purpose: Arbovirosis, viral infection transmitted by arthropods, is a widespread health problem. In Italy, as well for all Mediterranean basin, from late spring to the end of summer, Toscana Virus (TOSV), a sandfly borne virus, accounts for the majority of aseptic meningitis/meningoencephalitis cases. TOSV meningitis/meningoencephalitis has usually a self-extinguishing benign course. Our aim is to report a case of a young healthy women diagnosed with Toscana Virus meningoencephalitis with a complicated clinical course.Materials and methods/results: Case report of a 33-years old woman, admitted to the Infectious Diseases Unit at Careggi General Hospital (Florence-Italy), with a diagnosis of Toscana Virus meningoencephalitis. Seventy-two hours after the admission, she developed typical symptoms, as impaired legs coordination, slurred speech, stumbling and dysmetria, of acute cerebellar ataxia (ACA). Urgent neurological assessment was provided performing an electroencephalography study followed by a brain and brainstem magnetic resonance imaging. In the meanwhile, bilateral nystagmus arised. Through neurologist consultation ACA clinical diagnosis was then made and intravenous steroid therapy was administered with prompt symptoms resolution. The patient was finally discharged at day 10 since the ACA onset in good clinical conditions.Conclusions: To raise awareness among physicians about possible neurological complications during Toscana Virus meningoencephalitis.


Asunto(s)
Ataxia Cerebelosa/diagnóstico , Encefalitis por Arbovirus/diagnóstico , Meningitis Viral/diagnóstico , Meningoencefalitis/diagnóstico , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Enfermedad Aguda , Adulto , Ataxia Cerebelosa/etiología , Encefalitis por Arbovirus/complicaciones , Encefalitis por Arbovirus/virología , Femenino , Humanos , Meningitis Viral/complicaciones , Meningitis Viral/virología , Meningoencefalitis/complicaciones , Meningoencefalitis/virología , Enfermedades Raras
10.
Forensic Sci Med Pathol ; 16(4): 714-717, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32394206

RESUMEN

Meningoencephalitis is the most common neurological complication related to Epstein-Barr virus (EBV), and in immunocompetent adults, it is most commonly self-limited. We describe a case of fatal EBV infection characterized by meningoencephalitis, foci of myocarditis and interstitial nephritis in an immunocompetent 74-year-old man. The postmortem diagnosis was made based on the presence of EBV DNA in the cerebrospinal fluid and by immunohistochemical assay that showed spots of intracellular positivity to anti-EBV antibody in brain tissue.


Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Meningoencefalitis/virología , Anciano , ADN Viral/líquido cefalorraquídeo , Resultado Fatal , Herpesvirus Humano 4/genética , Humanos , Inmunocompetencia , Inmunohistoquímica , Masculino
11.
Emerg Infect Dis ; 25(2): 380-382, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30666950

RESUMEN

Oropouche fever is a neglected arthropodborne disease and zoonosis responsible for several outbreaks of a febrile disease in Central and South America. We present a clinical case of aseptic meningoencephalitis in an immunocompetent patient that resulted from Oropouche virus acquired in northern Brazil but diagnosed in a nonendemic region.


Asunto(s)
Infecciones por Bunyaviridae/diagnóstico , Infecciones por Bunyaviridae/virología , Meningoencefalitis/diagnóstico , Meningoencefalitis/virología , Orthobunyavirus , Adulto , Brasil/epidemiología , Infecciones por Bunyaviridae/epidemiología , Brotes de Enfermedades , Humanos , Masculino , Meningoencefalitis/epidemiología , Orthobunyavirus/genética , Reacción en Cadena de la Polimerasa , Vigilancia en Salud Pública , Tomografía Computarizada por Rayos X
12.
J Virol ; 92(3)2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29118127

RESUMEN

Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8+ T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4+ and CD8+ T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model.IMPORTANCE Rift Valley Fever (RVF) is an important emerging viral disease for which we lack both an effective human vaccine and treatment. Encephalitis and neurological disease resulting from RVF lead to death or significant long-term disability for infected people. African green monkeys (AGM) develop lethal neurological disease when infected with RVF virus by inhalation. Here we report the similarities in disease course between infected AGM and humans. For the first time, we examine the peripheral immune response during the course of infection in AGM and show that there are very early differences in the immune response between animals that survive infection and those that succumb. We conclude that AGM are a novel and suitable monkey model for studying the neuropathogenesis of RVF and for testing vaccines and therapeutics against this emerging viral pathogen.


Asunto(s)
Biomarcadores/sangre , Citocinas/sangre , Meningoencefalitis/patología , Fiebre del Valle del Rift/patología , Linfocitos T/inmunología , Animales , Anticuerpos Antivirales/inmunología , Caspasa 3/inmunología , Chlorocebus aethiops , Modelos Animales de Enfermedad , Femenino , Genes MHC Clase II , Humanos , Activación de Linfocitos , Meningoencefalitis/inmunología , Meningoencefalitis/virología , Fiebre del Valle del Rift/inmunología , Virus de la Fiebre del Valle del Rift/fisiología , Virión/inmunología
13.
J Neurovirol ; 25(4): 589-596, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31102186

RESUMEN

Human adenovirus (HAdV) has been recognized as a significant viral pathogen implicated in neurological diseases, particularly in immunocompromised patients. However, its involvement in meningoencephalitis remains unclear. The aim of this study was to investigate HAdV and other viral co-infections in the cerebrospinal fluid (CSF) of patients suspected of having either meningoencephalitis or encephalitis. A total of 373 CSF samples from patients under clinical suspicion of neurological viral infection were included in this study. HAdV was investigated by conventional or multiplex real-time PCR, for different time periods. The frequency of HAdV central nervous system (CNS) infection was 1.08%, predominating in female patients with a predisposing condition, and presented with HAdV encephalitis. HAdV CNS infection was found to occur during the months of autumn and winter. The frequency of HAdV detected in CSF positive samples increased after the change in the diagnostic method from conventional to multiplex real-time PCR. There were no specific NMRI or EEG characteristics and two CSF samples with HAdV encephalitis had normal CSF WBC count. There were two cases of co-infection with HIV; no other co-infections with enterovirus or herpes family viruses were detected. All patients had good outcome. Although HAdV is rarely observable in CNS infectious syndromes, it must be investigated particularly in immunocompromised patients.


Asunto(s)
Adenovirus Humanos/genética , ADN Viral/genética , Encefalitis Viral/diagnóstico , Meningitis Viral/diagnóstico , Meningoencefalitis/diagnóstico , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Estudios Transversales , ADN Viral/líquido cefalorraquídeo , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/patología , Encefalitis Viral/virología , Femenino , Humanos , Recuento de Leucocitos , Leucocitos/virología , Masculino , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/patología , Meningitis Viral/virología , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/patología , Meningoencefalitis/virología , Persona de Mediana Edad , Estudios Prospectivos , Estaciones del Año , Carga Viral
14.
J Neurovirol ; 25(4): 597-604, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31062246

RESUMEN

Bovine herpesvirus type 1 and type 5 (BoHV-1 and BoHV-5) are two alphaherpesviruses that affect cattle with two different syndromes. While BoHV-1 mainly produces respiratory symptoms, BoHV-5 is highly neuropathogenic and responsible for meningoencephalitis in young cattle. The latency-related (LR) gene, which is not conserved between these two herpesviruses, is the only viral gene abundantly expressed in latently infected neurons. The antiapoptotic action of this gene has been demonstrated during acute infection and reactivation from latency and seems to be mainly mediated by a LR protein (ORF-2) which is truncated in amino acid 51 in the case of BoHV-5. In this work, we show that the BoHV-5 LR gene is less efficient at cell survival and apoptosis inhibition in transient as well as in established neuronal cell lines compared to its BoHV-1 homolog. We hypothesize that the BoHV-5 LR gene may have novel functions that are lacking in the BoHV-1 LR gene and that these differences may contribute to its enhanced neuropathogenesis.


Asunto(s)
Infecciones por Herpesviridae/veterinaria , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 5/genética , Rinotraqueítis Infecciosa Bovina/metabolismo , Meningoencefalitis/veterinaria , Proteínas Virales/genética , Latencia del Virus/genética , Animales , Apoptosis/genética , Bovinos , Línea Celular , Expresión Génica , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Herpesvirus Bovino 1/crecimiento & desarrollo , Herpesvirus Bovino 1/metabolismo , Herpesvirus Bovino 5/crecimiento & desarrollo , Herpesvirus Bovino 5/metabolismo , Interacciones Huésped-Patógeno/genética , Rinotraqueítis Infecciosa Bovina/patología , Rinotraqueítis Infecciosa Bovina/virología , Meningoencefalitis/patología , Meningoencefalitis/virología , Neuronas/metabolismo , Neuronas/virología , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Virales/metabolismo , Activación Viral
15.
Microb Pathog ; 136: 103691, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31445121

RESUMEN

Bovine alphaherpesvirus types 1 (BoHV-1) and 5 (BoHV-5) are closely related alphaherpesviruses. BoHV-5 causes non-suppurative meningoencephalitis in calves. BoHV-1 is associated with several syndromes and, occasionally, can cause encephalitis. Although both viruses are neurotropic and they share similar biological properties, it is unknown why these alphaherpesviruses differ in their ability to cause neurological disease. Neural tissue samples were collected from BoHV-1- and BoHV-5-intranasally inoculated calves during acute infection, latency and reactivation and the levels of cyclins mRNA expression were analyzed by qRT-PCR. Striking differences in the levels of cyclins mRNA were particularly detected in trigeminal ganglion (TG). The expression levels of cyclins in TG during BoHV-5 latency suggest that these viruses utilize different strategies to persist in the host. It is apparent that a relationship between virus loads and cyclin mRNA levels can be established only during acute infection and other factors might be involved in the regulation of cell cycle components during BoHV latency and reactivation. Bovine alphaherpesviruses neuropathogenicity might be influenced by the differential control of cell cycle components by these herpesviruses. This is the first report on BoHV-5 modulation of cyclins expression in neural tissues from its natural host.


Asunto(s)
Enfermedades de los Bovinos/patología , Ciclinas/biosíntesis , Encefalitis Viral/veterinaria , Infecciones por Herpesviridae/veterinaria , Herpesvirus Bovino 1/crecimiento & desarrollo , Herpesvirus Bovino 5/crecimiento & desarrollo , Meningoencefalitis/veterinaria , ARN Mensajero/biosíntesis , Animales , Encéfalo/patología , Bovinos , Ciclinas/genética , Encefalitis Viral/patología , Perfilación de la Expresión Génica , Infecciones por Herpesviridae/patología , Meningoencefalitis/virología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
Pediatr Transplant ; 23(8): e13584, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31556188

RESUMEN

Cytomegalovirus encephalitis is a challenging life-threatening complication following hematopoietic stem cell transplantation for which medical treatment is usually ineffective or toxic. However, in recent years, adoptive T-cell therapy has been reported to provide a significant chance of cure for patients with viral infections. Herein, two cases of pediatric patients successfully treated with third-party donor-derived virus-specific T cells for CMV meningoencephalitis are reported.


Asunto(s)
Infecciones por Citomegalovirus/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Meningoencefalitis/terapia , Meningoencefalitis/virología , Complicaciones Posoperatorias/terapia , Complicaciones Posoperatorias/virología , Niño , Femenino , Humanos , Lactante , Masculino , Inducción de Remisión
18.
Vet Pathol ; 56(4): 604-608, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30917745

RESUMEN

Neurologic manifestations other than cerebellar hypoplasia are rarely associated with feline panleukopenia virus (FPV) infection in cats. Here the authors describe lymphoplasmacytic meningoencephalitis and neuronal necrosis in 2 cats autopsied after exhibiting ataxia and nystagmus. Gross changes consisted of cerebellar herniation through the foramen magnum, with flattening of cerebrocortical gyri and narrowing of sulci. Histologically, lymphoplasmacytic meningoencephalitis, extensive neuronal necrosis, and neuroaxonal degeneration with digestion chambers were present in the telencephalon and brain stem in both cats. Frozen brain tissue of both cats was positive for parvoviral antigen via fluorescent antibody testing, and formalin-fixed, paraffin-embedded tissue sections of brain were immunoreactive for parvovirus antigen and positive for parvoviral DNA on in situ hybridization. Frozen brain tissue from 1 case was positive for parvovirus NS1 and VP2 genes using conventional polymerase chain reaction, and subsequent DNA sequencing and phylogenetic analysis revealed that the viral strain was a FPV. Reverse transcription quantitative polymerase chain reaction on formalin-fixed, paraffin-embedded brain tissue revealed high levels of parvovirus in both cases, supporting an acute and active viral infection. Although rare, FPV infection should be considered in cases of lymphoplasmacytic meningoencephalitis and neuronal necrosis in cats.


Asunto(s)
Virus de la Panleucopenia Felina/aislamiento & purificación , Panleucopenia Felina/patología , Meningoencefalitis/veterinaria , Animales , Encéfalo/patología , Gatos , Panleucopenia Felina/diagnóstico , Panleucopenia Felina/virología , Virus de la Panleucopenia Felina/genética , Hibridación in Situ/veterinaria , Meningoencefalitis/diagnóstico , Meningoencefalitis/virología , Necrosis/veterinaria , Neuronas/patología , Reacción en Cadena de la Polimerasa/veterinaria
19.
Schweiz Arch Tierheilkd ; 161(1): 23-31, 2019 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-30602429

RESUMEN

INTRODUCTION: European hedgehogs (Erinaceus europaeus) have a high exposure to various ticks, which could transmit pathogens with direct health significance for the host and may have zoonotic potential. Tick-borne meningoencephalitis (FSME) is an important tick-borne disease in Switzerland, caused by the tick-borne encephalitis virus. About its occurrence in the European hedgehog population is little known. The present study examined various organs, blood and ticks of 65 European hedgehogs to obtain data of FSME virus presence in this species in Switzerland. Real-time RT-PCR from the lungs, liver, spleen and kidney of 56 hedgehogs and of 114 infesting ticks (Ixodes hexagonus or Ixodes ricinus) were used for the detection of viral RNA. In addition, 19 blood samples were tested for antibodies against FSME by ELISA. FSME virus antibodies were detected for the first time in the serum of a European hedgehog. Lung and spleen tissue samples of the same animal tested also weak virus positive on RT-PCR. Clinically, the hedgehog showed neurological symptoms, although these symptoms could have originated from an other diseases. No viral RNA was detected in any of the ticks. This study could not confirm if the meningoencephalitis in the hedgehog was triggered by the FSME viral infection. Nevertheless, the simultaneous detection of antibodies and virus RNA in the same animal makes the European hedgehog a competent host of the tick-borne encephalitis virus and leads to the assumption that this species can act as a reservoir.


INTRODUCTION: En raison du nombre élevé de tiques présents chez les hérissons d'Europe (Erinaceus europaeus), ces animaux sont fortement exposés aux différents pathogènes qu'ils transmettent, pathogènes qui, en plus de l'importance directe pour la santé de l'hôte, peuvent aussi avoir un potentiel en termes de zoonose. La méningo-encéphalite à tique est, en Suisse, une maladie importante transmise par les tiques. Elle est causée par le virus de la méningo-encéphalite verno-estivale. Son occurrence chez les hérissons d'Europe est jusqu'à maintenant peu connue. Au travers de l'étude des organes, du sang et des tiques provenant de 65 hérissons européens, il devrait pour la première fois être possible de se prononcer sur la présence du virus chez cette espèce en Suisse. La détection de l'ARN viral a été effectuée au moyen d'une RT-PCR en temps réel sur les poumons, le foie, la rate et les reins de 56 hérissons ainsi que sur un total de 114 tiques dont ils étaient porteurs, appartenant aux espèces Ixodes hexagonus ou Ixodes ricinus. En outre, 19 échantillons de sang ont été testés par ELISA pour des anticorps contre le virus. Dans la présente étude, des anticorps contre le virus de l'encéphalite à tiques dans le sérum d'un hérisson européen ont pu être détectés pour la première fois. Les échantillons de poumon et de rate du même animal ont également montré une faible présence virale. Le même hérisson a présenté des symptômes neurologiques, mais ceux-ci pouvaient également être associés à d'autres maladies. On n'a démontré la présence d'ARN viral chez aucune tique. La possibilité d'une encéphalite causée par l'infection virale chez les hérissons ne peut pas être confirmée ou exclues avec cette étude. La détection simultanée des anticorps et de l'ARN viral chez le même animal fait du hérisson européen non seulement un hôte compétent du virus de l'encéphalite verno-estivale mais donne également également à penser que cette espèce pourrait servir de réservoir.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas/aislamiento & purificación , Encefalitis Transmitida por Garrapatas/veterinaria , Erizos/virología , Meningoencefalitis/veterinaria , Animales , Anticuerpos Antivirales/sangre , Vectores Arácnidos/virología , Reservorios de Enfermedades/veterinaria , Reservorios de Enfermedades/virología , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/virología , Erizos/parasitología , Inmunoglobulina G/sangre , Ixodes/virología , Masculino , Meningoencefalitis/epidemiología , Meningoencefalitis/virología , ARN Viral/análisis , Suiza/epidemiología
20.
Rinsho Ketsueki ; 60(2): 124-129, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-30842379

RESUMEN

A 63-year-old woman was admitted to our hospital to receive a fourth course of modified rituximab-ESHAP chemotherapy for relapsed primary breast diffuse large B-cell lymphoma. She developed hemophagocytic lymphohistiocytosis (HLH) 20 days after admission. Polymerase chain reaction (PCR) detected cytomegalovirus (CMV) DNA in her peripheral blood; therefore, she was diagnosed with CMV-associated HLH and consequently treated with foscarnet (FCN). Her general condition and pancytopenia soon improved, and the antiviral drug was stopped for 1 week. However, she suddenly became disoriented 10 days later, and this condition rapidly worsened. Cerebrospinal fluid (CSF) examination revealed an elevated white blood cell count with lymphocytic predominance and a high CMV DNA load, prompting a final diagnosis of CMV meningoencephalitis. We began intravenous combination therapy with FCN and ganciclovir (GCV), and her conscious state gradually improved. CMV DNA sequencing did not reveal drug resistance associated with mutations, and intravenous GCV was stopped for 1 week. FCN treatment was then continued until CMV DNA was no longer detected in her CSF samples via PCR. CMV meningoencephalitis is a rare neurological infection complicated with hematological malignancy in non-transplant patients and can be serious and life-threatening with a high mortality rate. This infection requires a differential diagnosis of consciousness impairment that develops in a patient with lymphoid malignancy during chemotherapy.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Linfoma de Células B Grandes Difuso/virología , Meningoencefalitis/virología , Adulto , Niño , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , ADN Viral/sangre , Femenino , Foscarnet , Ganciclovir , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Persona de Mediana Edad , Terapia Recuperativa
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