RESUMEN

The 5' noncoding regions of the genomes of picornaviruses form a complex structure that directs cap-independent initiation of translation. This structure has been termed the internal ribosome entry site (IRES). The efficiency of translation initiation was shown, in vitro, to be influenced by the binding of cellular factors to the IRES. Hence, we hypothesized that the IRES might control picornavirus tropism. In order to test this possibility, we made a bicistronic construct in which translation of the luciferase gene is controlled by the IRES of Theiler's murine encephalomyelitis virus. In vitro, we observed that the IRES functions in various cell types and in macrophages, irrespective of their activation state. In vivo, we observed that the IRES is functional in different tissues of transgenic mice. Thus, it seems that the IRES is not an essential determinant of Theiler's virus tropism. On the other hand, the age of the mouse could be critical for IRES function. Indeed, the IRES was found to be more efficient in young mice. Picornavirus IRESs are becoming popular tools in transgenesis technology, since they allow the expression of two genes from the same transcription unit. Our results show that the Theiler's virus IRES is functional in cells of different origins and that it is thus a broad-spectrum tool. The possible age dependency of the IRES function, however, could be a drawback for gene expression in adult mice.

Asunto(s)

Genoma Viral , Virus Maus Elberfeld/fisiología , Picornaviridae/fisiología , Biosíntesis de Proteínas , Ribosomas/genética , Animales , Secuencia de Bases , Técnicas de Transferencia de Gen , Ratones , Datos de Secuencia Molecular , Tropismo , Replicación Viral/genética

Asunto(s)

Antibióticos Antineoplásicos/farmacología , Proteínas Bacterianas/farmacología , Mycoplasma/efectos de los fármacos , Péptidos Cíclicos , Fenómenos Fisiológicos de los Virus , Animales , Técnicas Bacteriológicas , Bovinos , Virus de la Diarrea Viral Bovina/fisiología , Herpesvirus Suido 1/fisiología , Humanos , Lipopéptidos , Virus Maus Elberfeld/fisiología , Ratones , Mycoplasma/aislamiento & purificación , Ácidos Mirísticos/farmacología , Parvovirus/fisiología , Cultivo de Virus , Virus/aislamiento & purificación

RESUMEN

The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC-B and EMC-DV is mainly caused by release of some viral inhibitory factors from lymphocytes or phagocytic cells. Mice were infected with EMC-B and their splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases the viral inhibitory substance (VIS) which is neither immunoglobulin nor interferon. VIS has inhibitory effects against EMC-D in several kinds of cell lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post-treatment studies, VIS remarkably decreased the incidence of both illness and death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS activities existed in supernatant and pellet prepared from ultracentrifugation, but the properties of their activities could be differentiated quantitatively and qualitatively. It is speculated that VIS may be composed of at least two factors even though interferon may partially participate in one component of supernatant. The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might be due to the inhibition of the virus replication by VIS.

Asunto(s)

Antivirales/metabolismo , Bazo/metabolismo , Animales , Antivirales/química , Antivirales/aislamiento & purificación , Infecciones por Cardiovirus/etiología , Infecciones por Cardiovirus/prevención & control , Fusión Celular , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/prevención & control , Estabilidad de Medicamentos , Calor , Hibridomas , Concentración de Iones de Hidrógeno , Interferones/metabolismo , Masculino , Virus Maus Elberfeld/patogenicidad , Virus Maus Elberfeld/fisiología , Ratones , Bazo/citología , Replicación Viral

RESUMEN

Theiler's murine encephalomyelitis virus is responsible for a chronic inflammatory demyelinating disease of the central nervous system of the mouse. The disease is associated with persistent viral infection of the spinal cord. Some strains of mice are susceptible to viral infection, and other strains are resistant. The effect of the genetic background of the host on viral persistence has not been thoroughly investigated. We studied the amount of viral RNA in the spinal cords of 17 inbred strains of mice and their F1 crosses with the SJL/J strain and observed a large degree of variability among strains. The pattern of viral persistence among mouse strains could be explained by the interaction of two loci. One locus is localized in the H-2D region of the major histocompatibility complex, whereas the other locus is outside this complex and is not linked to the Tcrb locus on chromosome 6.

Asunto(s)

Encéfalo/microbiología , ADN Viral/análisis , Antígenos H-2/genética , Complejo Mayor de Histocompatibilidad , Virus Maus Elberfeld/fisiología , Ratones Endogámicos/genética , ARN Viral/análisis , Médula Espinal/microbiología , Animales , Mapeo Cromosómico , Cruzamientos Genéticos , ADN/análisis , ADN/genética , ADN Viral/genética , Predisposición Genética a la Enfermedad , Virus Maus Elberfeld/patogenicidad , Ratones , Reacción en Cadena de la Polimerasa , ARN/análisis , ARN/genética , ARN Viral/genética , Especificidad de la Especie , Virulencia

RESUMEN

Western immunoblots of BHK-21 cell lysates probed with the highly virulent GDVII and the less virulent BeAn strains of Theiler's murine encephalomyelitis virus (TMEV) revealed predominant binding to a 34-kDa membrane protein and much lower levels of binding to 100- and 18-kDa membrane proteins. Complete inhibition of virus binding to both the 34- and 18-kDa membrane species by excess unlabeled TMEV demonstrated specificity of binding. Virus binding was also blocked by wheat germ agglutinin, which specifically binds to sialic acid residues and blocks TMEV binding to whole BHK-21 cells. Radiolabeled TMEV also bound to 100-, 34-, and 18-kDa membrane proteins expressed on other TMEV permissive cell lines but not on the nonpermissive cell lines tested. These data suggest that a 34-kDa cellular protein may be the primary determinant of susceptibility to TMEV infection by mediating the binding of GDVII and BeAn viruses to susceptible cells.

Asunto(s)

Virus Maus Elberfeld/fisiología , Receptores Virales/fisiología , Animales , Autorradiografía , Unión Competitiva , Línea Celular , Membrana Celular/fisiología , Cricetinae , Electroforesis en Gel de Poliacrilamida , Metionina/metabolismo , Peso Molecular , Fosfatos/metabolismo , Radioisótopos de Fósforo , Receptores Virales/biosíntesis , Receptores Virales/aislamiento & purificación , Radioisótopos de Azufre

RESUMEN

A murine model that demonstrated a placental barrier to fetal enterovirus infection in late pregnancy was extended to middle and early gestation. Inoculation with Theiler's murine encephalomyelitis virus (TMEV) in middle and early gestation infected 73% and 90% of placentas and 7% and 78% of fetuses, respectively. In situ hybridization (ISH) of tissues obtained after middle-gestation inoculation revealed TMEV in the placental decidua and spongiotrophoblast layers but generally not in the labyrinth (the layer adjacent to the fetus) or fetus (similar to late gestation). In contrast, ISH of placentas harvested after early-gestation inoculation identified TMEV predominantly in the labyrinth, in which vasculature was often replaced by hyalinized hemorrhagic tissue and small cell infiltrates; fetuses contained virus in heart, pericardium, great vessels, lung, pleura, brain, and liver. The placental barrier to enterovirus transmission appears to develop between early and middle gestation. Enterovirus infection before this time may induce placental damage, fetal infection, or both.

Asunto(s)

Infecciones por Enterovirus/microbiología , Enfermedades Fetales/microbiología , Virus Maus Elberfeld/fisiología , Placenta/microbiología , Complicaciones Infecciosas del Embarazo/microbiología , Animales , Modelos Animales de Enfermedad , Infecciones por Enterovirus/inmunología , Femenino , Enfermedades Fetales/inmunología , Virus Maus Elberfeld/genética , Ratones , Hibridación de Ácido Nucleico , Placenta/inmunología , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Sondas ARN , ARN Viral/análisis

RESUMEN

The Daniels strain of Theiler's murine encephalomyelitis produces a chronic disease which is an animal model for human demyelinating disorders. Previously, we selected a neutralization-resistant virus variant producing an altered and diminished central nervous system disease in immunocompetent mice which was evident during the later stage of infection (after 4 weeks) (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). The exact epitope determining neurovirulence was precisely mapped to a capsid protein, VP-1, and represents a neutralizing region (A. Zurbriggen, J. M. Hogle, and R. S. Fujinami, J. Exp. Med. 170:2037-2049, 1989). Here, we present experiments with immunoincompetent animals to determine viral replication, spread, and targeting to the central nervous system in the absence of detectable antibodies or functional T cells. Nude mice were infected orally, and the virus was monitored by plaque assay, immunohistochemistry, and in situ hybridization. Early during the infection (1 week), the variant virus induced an acute disease comparable to that induced by the wild-type virus in these nude mice. Alterations in tropism in the central nervous system were not apparent when wild-type parental Daniels strain virus was compared with the variant virus. Moreover, variant virus replicated in tissue culture (BHK-21 cells) to similarly high titers in a time course identical to that of the wild-type virus (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). However, replication of the variant virus versus the wild-type virus within the spinal cord of athymic nude mice infected per os was substantially restricted by 6 weeks postinfection. Therefore, the reduced neurovirulence in the later stage (6 weeks) of the disease is most likely due to a diminished growth rate or spread of the variant virus in the central nervous system rather than to marked differences in viral tropism.

Asunto(s)

Infecciones por Enterovirus/microbiología , Virus Maus Elberfeld/fisiología , Médula Espinal/microbiología , Replicación Viral , Animales , Línea Celular , Infecciones por Enterovirus/patología , Variación Genética , Virus Maus Elberfeld/genética , Ratones , Ratones Desnudos , Especificidad de la Especie , Médula Espinal/patología

RESUMEN

Three categories of cell lines are described with respect to their activity in binding Theiler's murine encephalomyelitis virus (TMEV). High, medium and low densities of viral receptors can be detected on cell lines from different species and origins by using an immunological binding assay. Nevertheless, TMEV acts as a fastidious virus that only infects a few cell types productively. No correlation between virion binding and degree of permissiveness to infection could be detected. The presence of viral receptors in both susceptible and resistant strains of mice seemed to have a widespread tissue distribution, the thymus being an exception. When primary cerebral cultures, enriched in neurons, astrocytes or oligodendrocytes, were checked in the immunological assay, a higher density of viral receptors was detected in the neuronal population. The number of virus-binding sites in the BHK-21 cell line is reported here to be 5 x 10(3) per cell; approximately 15 x 10(3) and 2.5 x 10(3) are the estimates of binding sites per cultured neuron and macroglial cell, respectively.

Asunto(s)

Virus Maus Elberfeld/fisiología , Receptores Virales/fisiología , Animales , Astrocitos/fisiología , Línea Celular , Células Cultivadas , Humanos , Ratones , Ratones Endogámicos BALB C , Neuronas/fisiología , Oligodendroglía/fisiología , Especificidad de Órganos , Ratas , Ratas Endogámicas , Especificidad de la Especie , Replicación Viral

RESUMEN

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26-20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence.

Asunto(s)

Transformación Celular Viral , Enfermedades Desmielinizantes/microbiología , Virus Maus Elberfeld/genética , Animales , Anticuerpos Antivirales/análisis , Antígenos Virales/análisis , Línea Celular , Enfermedades Desmielinizantes/patología , Femenino , Variación Genética , Glioma , Inmunoglobulinas/análisis , Virus Maus Elberfeld/patogenicidad , Virus Maus Elberfeld/fisiología , Ratones , Ratones Endogámicos , ARN Viral/análisis , Médula Espinal/microbiología , Médula Espinal/patología , Ensayo de Placa Viral , Virulencia/genética , Replicación Viral

RESUMEN

The cytotropism of two strains, GDVII and DA, of Theiler's murine encephalomyelitis viruses (TMEV) was studied in the oligodendrocyte-enriched murine neural cell cultures. Both GDVII and DA caused cytopathic effects in the neural cell cultures, and double immunostaining for galactocerebroside (Gal-Cer), a marker molecule for oligodendrocyte, and viral antigens disclosed a dual expression of Gal-Cer and viral antigens in over 80% of cells in both cultures 24 h after infection with either GDVII or DA. The kinetics of cell-free and cell-associated infectivity were not significantly different between two cultures. These in vitro observations suggest that neither replication in oligodendrocyte nor cell-associated infectivity is a sole factor in discriminating those two subgroups of TMEV with regard to the demyelinating activity, and that virus cell binding may play an important role in virus persistence and TMEV-induced demyelination.

Asunto(s)

Virus Maus Elberfeld/fisiología , Neuronas/microbiología , Animales , Antígenos Virales/biosíntesis , Movimiento Celular , Células Cultivadas , Efecto Citopatogénico Viral , Enfermedades Desmielinizantes , Femenino , Galactosilceramidas/biosíntesis , Cinética , Ratones , Ratones Endogámicos C3H , Neuronas/patología , Oligodendroglía/microbiología , Oligodendroglía/patología , Especificidad de la Especie , Replicación Viral

RESUMEN

Employing a murine model of multiple sclerosis which utilizes intracranial injection of Theiler's virus murine encephalomyelitis (TMEV) into SJL/J mice, we tested the potential role of tumor necrosis factor alpha (TNF-alpha) in ameliorating CNS demyelination. Infection with TMEV caused early grey matter inflammation (7 days post-infection) in the brain and spinal cord followed by chronic demyelination (35 days post-infection) in the spinal cord. Administration of recombinant human or mouse TNF-alpha starting 12 h prior to infection and then three times weekly had minimal effect on development of grey matter inflammation in the spinal cord. In contrast, TNF-alpha dramatically reduced demyelination present in spinal cord on days 14 and 35 after TMEV infection (P less than 0.01) when compared to controls. CNS virus titers of TMEV were not modified by TNF-alpha administration as measured on days 7, 14, and 35 following infection. In vivo administration of TNF-alpha inhibits TMEV-induced demyelination in susceptible SJL/J mice without affecting virus replication in the CNS.

Asunto(s)

Enfermedades Desmielinizantes/prevención & control , Infecciones por Enterovirus/prevención & control , Virus Maus Elberfeld , Factor de Necrosis Tumoral alfa/farmacología , Animales , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/patología , Infecciones por Enterovirus/etiología , Infecciones por Enterovirus/patología , Femenino , Virus Maus Elberfeld/efectos de los fármacos , Virus Maus Elberfeld/fisiología , Ratones , Factores de Tiempo , Replicación Viral/efectos de los fármacos

RESUMEN

Infection of athymic (nu/nu) mice with Theiler's murine encephalomyelitis virus results in an acute encephalitis which resembles poliomyelitis. Immunohistochemistry and in situ hybridization were used to delineate the presence of viral proteins and RNA in the nervous systems of nude mice infected with the Daniels strain of Theiler's virus. This system permits the analysis of a viral infection in the absence of an effective immune response. By immunohistochemistry, viral antigen was found in the processes and cell bodies of neurons and glial cells. Besides the presence of viral antigen in these cell types, by in situ hybridization, Theiler's virus RNA was also found in cells associated with vascular endothelium in the brains and spinal cords of these infected mice. Theiler's virus RNA-positive endothelial cells were observed not only near the primary lesions but also away from demonstrable lesions in normal-appearing regions in the central nervous system. Earlier work had suggested an intra-axonal dissemination for this virus (M. C. Dal Canto and H. L. Lipton, Am. J. Pathol. 106:20-29, 1982). Our findings are consistent with this model but also suggest an additional mechanism for virus spread within the central nervous system, i.e., by infecting vascular cells and crossing the blood-brain barrier. Lastly, after Theiler's murine encephalomyelitis virus infection, not only glial cells but also endothelial cells express major histocompatibility complex class II (la) antigen on their surface (M. Rodriguez, M. L. Pierce, and E. A. Howie, J. Immunol. 138:3438-3442, 1987). Our demonstration of Theiler's virus-infected endotheliumlike cells may explain interactions of virus products in stimulating antigen presentation.

Asunto(s)

Endotelio Vascular/microbiología , Infecciones por Enterovirus/microbiología , Enterovirus/genética , Virus Maus Elberfeld/genética , ARN Viral/análisis , Animales , Antígenos Virales/análisis , Encéfalo/irrigación sanguínea , Encéfalo/microbiología , Línea Celular , Femenino , Hipocampo/análisis , Hipocampo/microbiología , Inmunohistoquímica , Virus Maus Elberfeld/crecimiento & desarrollo , Virus Maus Elberfeld/inmunología , Virus Maus Elberfeld/fisiología , Ratones , Ratones Desnudos , Neuroglía/análisis , Neuroglía/microbiología , Neuronas/análisis , Neuronas/microbiología , Hibridación de Ácido Nucleico , Médula Espinal/análisis , Médula Espinal/irrigación sanguínea , Médula Espinal/microbiología , Ensayo de Placa Viral , Proteínas Virales/análisis

RESUMEN

Theiler's murine encephalomyelitis virus (TMEV) gives rise to a biphasic disease of the central nervous system (CNS) following intracranial inoculation of susceptible strains of mice. The early phase, during the first month, resembles poliomyelitis and in the late phase the mice suffer from inflammatory demyelination reminiscent of multiple sclerosis. In order to investigate the role of helper T cells in the acute and chronic phases of the disease we depleted mice of their L3T4 T cells in vivo with rat monoclonal antibodies, prior to infection and prior to the onset of clinical signs of demyelination. Mice depleted of their helper cells failed to produce antibodies to TMEV and consequently were unable to clear virus from the CNS and died within the first month of infection. Depletion of T cells before the demyelinating phase of the disease resulted in a marked decrease in the incidence of disease from 77% of the immunocompetent animals with clinical signs of paralysis to 36%. Immunocompetent TMEV-infected mice also developed antibodies against myelin suggesting that autoimmune mechanisms may play a role in TMEV-induced demyelination.

Asunto(s)

Enfermedades Desmielinizantes/etiología , Infecciones por Enterovirus/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Autoanticuerpos/análisis , Encéfalo/microbiología , Enfermedades Desmielinizantes/inmunología , Femenino , Virus Maus Elberfeld/inmunología , Virus Maus Elberfeld/fisiología , Ratones , Ratones Endogámicos CBA , Vaina de Mielina/inmunología , Médula Espinal/microbiología , Replicación Viral

RESUMEN

Theiler's murine encephalomyelitis viruses causing both fatal encephalitis (GDVII virus) and chronic demyelinating disease (WW virus) are capable of replicating in isolated Schwann cell cultures. Light microscopy combined with immunohistochemical staining of viral antigens revealed that large numbers of Schwann cells infected with the two viruses show cytopathic effect (rounding) and contain viral antigens. Electron microscopy of virus-infected Schwann cells shows that the morphological alterations that the cells undergo following infection by the two virus isolates are different. In the early stages of GDVII and WW virus infection, different inclusion bodies are formed in the cells cytoplasm. At late stages of the infection GDVII virions are found in all infected cells and are arranged in crystalline arrays around inclusion bodies. In contrast, in WW virus-infected Schwann cells only in few cells virions were observed and they appeared aligned between two membrane units.

Asunto(s)

Enterovirus/ultraestructura , Virus Maus Elberfeld/ultraestructura , Células de Schwann/microbiología , Replicación Viral , Animales , Separación Celular , Células Cultivadas , Cricetinae , Técnica del Anticuerpo Fluorescente , Técnicas para Inmunoenzimas , Virus Maus Elberfeld/fisiología , Ratones , Microscopía Electrónica de Rastreo , Células de Schwann/ultraestructura

RESUMEN

Demyelination was produced in mice by intracerebral inoculation of Theiler's murine encephalomyelitis virus. The earliest ultrastructural changes occurred in the inner cytoplasmic tongues of oligodendrocytes, the most distal extension of these cells. Viral antigen was localized to glial loops that connect with myelin lamellae. This study indicates that a "dying-back" process may occur in virus-infected oligodendrocytes, which then results in demyelination.

Asunto(s)

Enfermedades Desmielinizantes/microbiología , Infecciones por Enterovirus/complicaciones , Neuroglía/patología , Oligodendroglía/patología , Animales , Transformación Celular Viral , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/patología , Infecciones por Enterovirus/patología , Virus Maus Elberfeld/fisiología , Ratones , Ratones Endogámicos , Microscopía Electrónica , Oligodendroglía/microbiología , Oligodendroglía/ultraestructura , Médula Espinal/patología

RESUMEN

Genetic control of resistance and susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice was examined. Mice derived from various crosses between susceptible SJL (S) and resistant C57BL/6 (B6) strains allowed determination of the relative susceptibility contributed by H-2 and non-H-2 genes, as well as allowing segregation of H-2 linked genes. Six of 39 B6SF1 hybrid progeny developed disease, suggesting several possibilities--resistance is dominant and susceptibility recessive but with incomplete penetrance, the incidence of disease is dose dependent and is dictated by the number of "susceptible/resistant" alleles present at one or more loci, or some combination of the two. Data involving the progeny from the B6SF1 hybrids mated to the S parental strain indicated the involvement of more than one locus. The strong correlation between the number of H-2s haplotypes and the incidence of demyelinating disease suggested that at least one of the genes was linked to the H-2 complex; however, other independently segregating (unlinked) loci strongly affected the disease incidence among H-2 identical animals. A gene or genes from the S background was also associated with enhanced virus growth or diminished virus clearance in the central nervous system (CNS). Overall, the observations support a gene dosage model for susceptibility that relates disease incidence to the total number of S alleles at both H-2 and non-H-2 loci.

Asunto(s)

Enfermedades Desmielinizantes/genética , Infecciones por Enterovirus/genética , Animales , Cruzamientos Genéticos , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/patología , Susceptibilidad a Enfermedades , Infecciones por Enterovirus/complicaciones , Infecciones por Enterovirus/patología , Femenino , Antígenos H-2/genética , Inmunidad Innata , Masculino , Virus Maus Elberfeld/fisiología , Ratones , Ratones Endogámicos , Médula Espinal/microbiología , Replicación Viral

RESUMEN

This study has demonstrated that the ability of BeAn 8386 virus to persist in the central nervous system of mice declines with the increasing age of the host at the time of inoculation. Although persistent infection was established in 1-, 3-, 9-, and 40-week-old mice, there was a significant reduction in both the frequency of virus isolations and the mean virus titers in mice inoculated after 3 weeks of age. The incidence of clinical demyelinating disease (late disease) also decreased in animals infected after 3 weeks of age in parallel with the decline in virus persistence.

Asunto(s)

Encéfalo/microbiología , Enterovirus/aislamiento & purificación , Virus Maus Elberfeld/aislamiento & purificación , Envejecimiento , Animales , Encéfalo/crecimiento & desarrollo , Masculino , Virus Maus Elberfeld/fisiología , Ratones