RESUMEN
BACKGROUND: Toscana virus (TOSV) is a Phlebovirus transmitted to humans by phlebotomines and represent an etiological agent of acute aseptic meningitis (AAM) in countries where the virus is endemic, including Italy. Incidence of TOSV infections is closely associated with the geographical distribution of the phlebotomine vectors which in turn is affected by climate changes that determine survival and spread. As a result, TOSV infections show a seasonal trend with a peak of incidence in summer months. OBJECTIVES: To measure the prevalence of TOSV infections in AAM patients in central Italy and evaluate the climate changes in phlebotomine vectors ecology and virus propagation. STUDY DESIGN: One thousand and seventy-three cerebrospinal fluid samples (CSFs), collected from patients with suspected viral meningitis, were collected over nine years (2011-2019) during the May to October period and tested for viruses most commonly associated with AAM. Serum samples addressed to the Microbiology and Virology Unit of "S. Maria delle Scotte" Hospital for confirmation acute TOSV infection (n = 324) were tested for TOSV-specific IgM and IgG. RESULTS: Among the CSF samples, 1.3% were positive for Enteroviruses; 0.9% for Varicella zoster virus, 1.9% for Herpes simplex virus type-1/2 and 4.6% for TOSV. Serum IgM analyses disclosed TOSV-specific IgM in 27.1% of sera suggesting the predominant involvement of TOSV in neuroinvasive infections. CONCLUSIONS: This data confirms the predominant role of TOSV as causative agent of AAM during the summer time in endemic countries. Moreover, climate changes affecting phlebotomine vectors persistence, reproduction and activity could be involved in the cyclic nature of TOSV infection reported during the last nine years.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Bunyaviridae/epidemiología , Infecciones por Bunyaviridae/transmisión , Meningitis Viral/epidemiología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adolescente , Adulto , Factores de Edad , Femenino , Geografía , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Italia/epidemiología , Masculino , Persona de Mediana Edad , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Factores Sexuales , Adulto JovenRESUMEN
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 RarasRESUMEN
Toscana virus (TOSV) is a Phlebovirus responsible for human neurological infections in endemic Mediterranean areas. The main viral target is the central nervous system, with viremia as a way of dissemination throughout the host. This study was aimed at understanding the spread of TOSV in the host by identifying the cell population infected by the virus and the vehicle to the organs. In vivo studies provided evidence that endothelial cells are infected by TOSV, indicating their potential role in the diffusion of the virus following viremic spread. These results were further confirmed in vitro. Human peripheral mononuclear blood cells were infected with TOSV; only monocyte-derived dendritic cells were identified as susceptible to TOSV infection. Productive viral replication was then observed in human monocyte-derived dendritic cells (moDCs) and in human endothelial cells by recovery of the virus from a cell supernatant. Interleukin-6 was produced by both cell types upon TOSV infection, mostly by endothelial cells, while moDCs particularly expressed TNF-α, which is known to induce a long-lasting decrease in endothelial cell barrier function. These cells could therefore be implicated in the spread of the virus in the host and in the infection of tissues that are affected by the disease, such as the central nervous system. The identification of in vitro and in vivo TOSV cell targets is an important tool for understanding the pathogenesis of the infection, providing new insight into virus-cell interaction for improved knowledge and control of this viral disease.
Asunto(s)
Infecciones por Bunyaviridae/virología , Células Dendríticas/virología , Células Endoteliales/virología , Interacciones Huésped-Patógeno , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Replicación Viral/genética , Animales , Infecciones por Bunyaviridae/metabolismo , Infecciones por Bunyaviridae/patología , Diferenciación Celular , Permeabilidad de la Membrana Celular , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/virología , Chlorocebus aethiops , Células Dendríticas/metabolismo , Células Endoteliales/metabolismo , Femenino , Humanos , Interleucina-6/biosíntesis , Ratones , Ratones Endogámicos BALB C , Monocitos/metabolismo , Monocitos/virología , Cultivo Primario de Células , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/fisiología , Factor de Necrosis Tumoral alfa/biosíntesis , Células VeroAsunto(s)
Fascitis/etiología , Miositis/etiología , Fiebre por Flebótomos/complicaciones , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Anticuerpos Antivirales/sangre , Enfermedades Transmisibles Emergentes , Fascitis/patología , Fascitis/virología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miositis/patología , Miositis/virología , Fiebre por Flebótomos/diagnóstico , Polineuropatías/etiología , Polineuropatías/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidadRESUMEN
Toscana virus (TOSV) is an emerging pathogen in the Mediterranean basin where it causes summertime outbreaks of aseptic meningitis and meningoencephalitis. Many aspects of TOSV biology remain unknown including the possible implication of an amplifying mammalian host besides its vector. The three experiments described here were designed to assess the relationship between TOSV and type-I interferon (IFN) response. The main findings were as follows. First, TOSV growth in Vero cells is sensitive to an antiviral state induced by low-dose addition of exogenous IFN beta (IFN-ß) (10IU/ml). Second, no IFN-ß mRNA or IFN-ß was detectable after infection of HeLa and 293T cells by TOSV. Finally, TOSV inhibits IFN-ß production induced by Sendaï virus, a well known inducer of IFN-ß production. In addition to showing that TOSV can inhibit the IFN-ß response, these findings suggest that anti-IFN capability is maintained by regular contact with that of a mammalian host.
Asunto(s)
Interacciones Huésped-Patógeno , Interferón beta/antagonistas & inhibidores , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Animales , Línea Celular , Chlorocebus aethiops , Humanos , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidadRESUMEN
Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-ß) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92:71-79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-ß promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-ß promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response.
Asunto(s)
Interferón Tipo I/antagonistas & inhibidores , Receptores de Ácido Retinoico/metabolismo , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Proteínas no Estructurales Virales/metabolismo , Animales , Chlorocebus aethiops , Células HEK293 , Humanos , Interferón Tipo I/biosíntesis , Datos de Secuencia Molecular , Receptores de Ácido Retinoico/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/metabolismo , Análisis de Secuencia de ADN , Células Vero , Proteínas no Estructurales Virales/genéticaRESUMEN
Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-ß gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.
Asunto(s)
Encéfalo/virología , Enfermedades del Sistema Nervioso/virología , Fiebre del Valle del Rift/prevención & control , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Vacunas Atenuadas/efectos adversos , Proteínas no Estructurales Virales/metabolismo , Vacunas Virales/efectos adversos , Animales , Línea Celular , Chlorocebus aethiops , Femenino , Humanos , Inmunoglobulina G/sangre , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Fiebre del Valle del Rift/inmunología , Virus de la Fiebre del Valle del Rift/inmunología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Vacunación , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Células Vero , Proteínas no Estructurales Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunologíaRESUMEN
BACKGROUND: Toscana virus (TOSV) is an emerging pathogen causing central nervous system (CNS) infection in Mediterranean countries, mostly during summer season. OBJECTIVES: To compare the clinical and laboratory characteristics of Toscana CNS infections to the most common viral pathogens seen in the United States. STUDY DESIGN: We performed a case series of patients with 41 TOSV infection and compared the clinical characteristics, laboratory findings, imaging results and clinical outcomes to the most commonly recognized viral causes of meningoencephalitis in the US [enterovirus (n=60), herpes simplex virus (n=48), and West Nile virus (n=30)] from our multi-center study of patients with aseptic meningoencephalitis syndromes in the Greater Houston area. RESULTS: TOSV infection occurs in different age groups compared to enterovirus, HSV, and WNV. All infections most frequently occur during summer-fall except HSV which distributes throughout the year. All patients with TOSV had history of travel to endemic areas. There are differences in clinical presentation and CSF findings comparing TOSV and enterovirus, HSV, and WNV infection. There are no significant differences in outcomes of each infection except WNV meningoencephalitis which had a poorer outcome compared to TOSV infection. CONCLUSIONS: TOSV is an emerging pathogen that should be considered in the differential diagnosis of patients with CNS infections and a recent travel history to endemic areas.
Asunto(s)
Infecciones por Bunyaviridae/patología , Infecciones por Bunyaviridae/virología , Meningoencefalitis/patología , Meningoencefalitis/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Bunyaviridae/diagnóstico , Niño , Preescolar , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/patología , Enfermedades Transmisibles Emergentes/virología , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Meningoencefalitis/diagnóstico , Persona de Mediana Edad , Texas , Resultado del TratamientoAsunto(s)
Líquido Cefalorraquídeo/diagnóstico por imagen , Hidrocefalia/virología , Meningoencefalitis/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adulto , Humanos , Hidrocefalia/líquido cefalorraquídeo , Hidrocefalia/complicaciones , Hidrocefalia/diagnóstico por imagen , Masculino , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/complicaciones , Meningoencefalitis/diagnóstico por imagen , Neuroimagen/métodos , CintigrafíaRESUMEN
Toscana virus (TOSV) infection is a frequent cause of meningitis in central Italy during summer. The disease generally has a benign course. Rarely, the infection produces a severe disease, with encephalitis and signs of systemic involvement, including lymphadenopathy. Since there is no clinical necessity of performing lymph node biopsy in such cases, the histopathological feature of TOSV-related lymphadenitis is not known. We herein present a case in which lymphadenopathy preceded the onset of meningitis. The excised lymph node showed a non-specific mixed-type lymphoid hyperplasia, with follicular hyperplasia, sinusal expansion and paracortical involvement. We also demonstrated the presence of viral protein and viral RNA in the lymph node tissue.
Asunto(s)
Ganglios Linfáticos/patología , Enfermedades Linfáticas/patología , Fiebre por Flebótomos/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adulto , Antibacterianos/uso terapéutico , Antipiréticos/uso terapéutico , Biopsia , Humanos , Hiperplasia , Inmunohistoquímica , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/virología , Enfermedades Linfáticas/tratamiento farmacológico , Enfermedades Linfáticas/virología , Masculino , Fiebre por Flebótomos/complicaciones , Fiebre por Flebótomos/tratamiento farmacológico , ARN Viral/aislamiento & purificación , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genéticaRESUMEN
Sandfly fever viruses (SFV) are endemic in the Mediterranean, Middle East, northern African and western Asian countries. Toscana virus (TOSV), serotype of Sandfly fever Naples virus, is among of the three most prevalent viruses associated with meningitis during the warm seasons in northern Mediterranean countries. The historical data of the sandfly fever (Pappataci fever) indicates its origin in Bosnia and Herzegovina at the end of 19th century. There is a long period of time for which there are no data on research related to the SFV in Bosnia and Herzegovina. The purpose of the study was to investigate the presence of sandfly fever in Bosnia and Herzegovina in recent years. The 68 of serum samples were obtained from February 2006 until September 2008 from a group of patients with febrile illness of unknown etiology. The sera were tested on the presence of IgG and IgM antibodies against TOSV by specific serology test- recomLine Bunyavirus IgG/IgM immuno-line assay. The recent TOSV-infection was confirmed in the patients in each year during the study: 10,71% (3/28) in 2008; 9,38% (3/32) in 2007 and 12,50% (1/8) in 2006. The presence of specific antibodies to TOSV in the sera of the patients in recent years indicates re-emerging character of the disease in this region. It would be necessary to make biological, epidemiological and clinical research on the TOSV and related phleboviruses to elucidate the problem of SFV in Bosnia and Herzegovina.
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Fiebre de Origen Desconocido/epidemiología , Fiebre por Flebótomos/epidemiología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Anticuerpos Antivirales/sangre , Bosnia y Herzegovina/epidemiología , Fiebre de Origen Desconocido/sangre , Fiebre de Origen Desconocido/etiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Fiebre por Flebótomos/sangre , Fiebre por Flebótomos/complicaciones , Prevalencia , Estudios Retrospectivos , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Estaciones del AñoAsunto(s)
Infecciones por Bunyaviridae/fisiopatología , Exantema , Isquemia , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Bunyaviridae/virología , Exantema/fisiopatología , Exantema/virología , Femenino , Humanos , Inmunoglobulina M/sangre , Isquemia/fisiopatología , Isquemia/virología , Masculino , Meningitis Aséptica/fisiopatología , Meningitis Aséptica/virología , Persona de Mediana Edad , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Análisis de Secuencia de ADN , España/epidemiologíaAsunto(s)
Infecciones por Bunyaviridae/complicaciones , Meningitis Viral , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Animales , Infecciones por Bunyaviridae/diagnóstico , Humanos , Masculino , Meningitis Viral/diagnóstico , Meningitis Viral/etiología , Meningitis Viral/virología , Persona de Mediana Edad , EspañaRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Meningitis/etiología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Meningitis/diagnóstico , Infecciones por Bunyaviridae/diagnósticoRESUMEN
Toscana virus (TOSV) is an arthropod-borne virus first identified in 1971 from the sandfly Phlebotomus perniciosus in central Italy. Many case reports in travelers and clinical research and epidemiologic studies conducted around the Mediterranean region have shown that TOSV has a tropism for the central nervous system (CNS) and is a major cause of meningitis and encephalitis in countries in which it circulates. In central Italy, TOSV is the most frequent cause of meningitis from May to October, far exceeding enteroviruses. In other northern Mediterranean countries, TOSV is among the 3 most prevalent viruses associated with meningitis during the warm seasons. Therefore, TOSV must be considered an emerging pathogen. Here, we review the epidemiology of TOSV in Europe and determine questions that should be addressed in future studies. Despite increasing evidence of its major role in medicine as an emerging cause of CNS infections, TOSV remains an unstudied pathogen, and few physicians are aware of its potential to cause CNS infections.
Asunto(s)
Fiebre por Flebótomos/epidemiología , Animales , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/virología , Encefalitis Viral/epidemiología , Encefalitis Viral/fisiopatología , Encefalitis Viral/virología , Europa (Continente)/epidemiología , Humanos , Meningitis Viral/epidemiología , Meningitis Viral/fisiopatología , Meningitis Viral/virología , Fiebre por Flebótomos/diagnóstico , Fiebre por Flebótomos/fisiopatología , Fiebre por Flebótomos/virología , Psychodidae/virología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/clasificación , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/genética , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidadRESUMEN
Las arbovirosis, infecciones virales transmitidas por artrópodos, son un problema de salud de ámbito mundial. La reaparición de brotes de algunas de ellas, como el dengue o la encefalitis por el virus del Nilo occidental, en regiones en las que no son habituales, justifica la necesidad de establecer medidas globales para su control.En Europa, las arbovirosis más frecuentes son: encefalitis transmitida por garrapatas (Tick borne encephalitis [TBE]), fiebre transmitida por flebotomos (sand fly fever Nápoles, Sicilia y Toscana) y ocasionalmente virus del Nilo occidental y fiebre de Crimea-Congo; aunque se ha detectado una circulación de otros virus potencialmente patógenos como Chikungunya. En España, la única arbovirosis autóctona descrita es la infección por el virus de Toscana, que produce meningitis linfocitaria de evolución benigna; no obstante, la presencia del virus del Nilo occidental asociado a meningoencefalitis en Francia, Portugal y países del Magreb incrementa el riesgo de su aparición esporádica en nuestro medio. Para su diagnóstico se requiere un alto índice de sospecha clínica y realización de técnicas específicas de laboratorio, fundamentalmente: detección de inmunoglobulina M (IgM), transcripción inversa-reacción en cadena de la polimerasa (RT-PCR) y cultivo viral en líquido cefalorraquídeo (LCR) y/o suero (AU)
Arbovirosis, viral infection transmitted by arthropods, is a widespread health problem. Recurrent outbreaks caused by some of these viruses such as dengue or West Nile strains in regions where they do not appear frequently, justify the establishment of global control measures. Tick-borne encephalitis viruses, sand fly fever viruses (Toscana, Naples and Sicily) and occasionally West Nile and Crimean-Congo fever viruses are the most frequent causes of arbovirosis in Europe, although circulation of other potentially pathogenetic viruses such as Chikungunya has also been detected. The only native arbovirosis described in Spain is infection produced by Toscana virus, which causes aseptic, usually benign meningitis. Nevertheless, some West Nile virus-associated meningo-encephalitis cases have been described in France, Portugal and countries in the Magreb region, increasing the risk of sporadic occurrence of these processes in our country. To achieve an accurate diagnosis, high clinical suspicion is required as well as highly specific laboratory techniques, mainly based on IgM detection, RT-PCR and viral culture of CSF and/or serum (AU)
Asunto(s)
Humanos , Fiebre del Nilo Occidental/epidemiología , Infecciones por Arbovirus/epidemiología , Fiebre por Flebótomos/epidemiología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Virus del Nilo Occidental/patogenicidad , Arbovirus/patogenicidad , Vectores de Enfermedades , Reservorios de EnfermedadesRESUMEN
Toscana virus (TOSV) has recently been recognized as an emerging virus transmitted by phlebotomus vectors, responsible for acute neurological diseases in Mediterranean countries. In our study, we demonstrated that adult Balb/c mice were susceptible to TOSV when infected intracerebrally (i.c.) or subcutaneously (s.c.) with a neuroadapted strain of the virus. We have shown that by performing serial passages of a wild type human isolate of TOSV in mouse brains, selection occurs for a highly virulent variant which replicates efficiently in the central nervous system (CNS) of i.c.-injected mice, causing acute encephalitis and death. Immunohistochemical analysis and TUNEL assay of post-mortem organs showed that TOSV replication was highly restricted to neurons in which it induced apoptotic death; however, virus antigen-positivity was also observed in the spleen and lymph nodes. In s.c.-injected mice, virus was detectable in the spleen and lymph nodes, whereas only few meningeal cells and neurons were affected, allowing for the mouse survival the infection. The presence of TOSV in spleen and lymph node cells in both s.c.- and i.c.-treated mice suggests their possible involvement in the diffusion of the infection. This animal model may be helpful for the development of prophylactic measures against TOSV infections.
Asunto(s)
Infecciones por Bunyaviridae/fisiopatología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Animales , Animales Recién Nacidos , Apoptosis , Encéfalo/patología , Encéfalo/virología , Infecciones por Bunyaviridae/inmunología , Infecciones por Bunyaviridae/patología , Infecciones por Bunyaviridae/virología , Línea Celular , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos BALB C , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Viremia , Replicación ViralRESUMEN
To evaluate, for the first time, circulation and clinical expression of Toscana virus (ToSv) in Umbria region we studied: (1) 93 cases of aseptic meningitis and meningoencephalitis admitted to our Department from 1989 to 2001 with negative results for common neurotropic virus; (2) 50 healthy subjects. Specific antibodies (IgM and IgG) anti-TOSv were found in 36.6% of aseptic meningitis, in 6.06% of meningoencephalitis and (IgG) in 16% of healthy subjects.
Asunto(s)
Meningitis/sangre , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/patogenicidad , Adolescente , Adulto , Anciano , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Italia/epidemiología , Masculino , Meningitis/epidemiología , Meningitis/virología , Meningoencefalitis/sangre , Meningoencefalitis/epidemiología , Meningoencefalitis/virología , Persona de Mediana Edad , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/inmunología , Virus de Nápoles de la Fiebre de la Mosca de los Arenales/aislamiento & purificación , Estudios SeroepidemiológicosRESUMEN
Toscana virus (TOSV) is a member of the genus Phlebovirus that is transmitted to humans by two different species of sand fly and causes acute aseptic meningitis (AAM) and meningoencephalitis in Central Italy. Fifteen cases of AAM due to TOSV have been found at the Spanish province of Granada, but no data regarding the presence of TOSV-related disease in other regions of Spain have been still reported. A collection of 88 serum and 53 cerebrospinal fluid (CSF) samples taken from 81 selected patients with AAM of unknown aetiology, residing at Madrid or at the southern Mediterranean coast of Spain, was retrospectively studied for presence of TOSV-specific antibodies from both IgG and IgM classes. Anti-TOSV IgG was also investigated in 457 serum samples from healthy individuals, aged 2-60 years, residing at the south of the Region of Madrid. Specific IgM in serum and/or intrathecally produced anti-TOSV IgG were detected in seven patients, three residents from the Mediterranean region and the remainder four from the Region of Madrid. The overall prevalence of anti-TOSV among the healthy population studied was 5%. These results confirm the role of TOSV as an agent causing AAM in the Spanish Mediterranean coast, extend these findings to the central region of the country and suggest that TOSV might be producing infection and neurological disease in every area of Spain harbouring significant populations of the viral vectors.