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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of the retina with herpes simplex virus type 1 (HSV-1) causes devastating lesions usually leading to blindness. However, the interactions between individual retinal cell types and this virus have not been well characterized, probably because of limitations posed by the complexity of the intact retina. We have now approached this problem through the use of separate, purified populations of isolated chick embryo retinal neurons and photoreceptor cells, of glial cells, and of pigmented epithelial cells. This manuscript deals with the initial part of these studies, aimed at determining the susceptibility of different retinal types to HSV-1 infection. The different cultures were exposed to HSV-1 for 3-48 hr, and cell infection was evaluated by immunocytochemical detection of viral antigens or by autoradiographic study of viral DNA replication. Practically 100% of the retinal glial cells and pigmented epithelial cells appeared susceptible to HSV-1 infection. On the other hand, as many as 70% of the neurons present in glia-free, pigment epithelium-free cultures, also appeared infected after a 24-hr exposure to the virus. Neuronal susceptibility to HSV-1 was already present in early (2-day) cultures, was time- and concentration-dependent, and led to neuronal degeneration after 24-48 hr. Neuronal infection was also corroborated by the detection of viral particles by transmission electron microscopy. Photoreceptor cells were consistently and selectively resistant to HSV-1 infection at all the concentrations and time points investigated. Both immunocytochemical and autoradiographic studies showed similar results. Photoreceptor resistance to HSV-1 appears to be selective, since they could be readily infected with RNA viruses such as vesicular stomatitis virus and influenza virus. These cell culture preparations offer an attractive system for the investigation of cellular mechanisms involved in the differential susceptibility of retinal cells to viral infection. Moreover, they could also help in the screening of treatments potentially capable of preventing and (or) curing HSV-induced retinal infection.
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PMID:Differential sensitivity of cultured retinal neurons and photoreceptors to herpes simplex infection. 282 Jul 71

To determine whether central neuropathogenesis associated with vesicular stomatitis virus (VSV) infection is regulated by T cells, we have examined the effects of intranasal infection of mice lacking T cells. The mice examined were of two kinds: (i) thymus-deficient BALB/c nu/nu nice and (ii) BALB/c mice experimentally depleted of T cells by systemic infusions of a monoclonal antibody to the CD4 or CD8 cell surface molecules. These mice were infected intranasally with a single dose of replication-competent VSV. Brain tissue homogenates were analyzed for the presence of infectious virus. For each population of mice, infection-related mortality was assessed. In histological sections of brain, the distribution of viral antigens (Ags) was examined by immunocytochemistry. We found that recovery of infectious virus from homogenates of tissues obtained from athymic nu/nu animals was more than 10 times greater than that from samples from their euthymic littermates. With a single exception in a BALB/c nu/nu mouse, virus was not isolated from the spleen when it was administered intranasally. In these experimental infections, athymic mice succumbed 1 to 2 days before their euthymic littermates. A dose of virus that resulted in half of the nu/+ survival rate was uniformly lethal to nu/nu mice. In experiments with BALB/c mice depleted of either CD4+ or CD8+ T cells by in vivo antibody treatment, histological analysis revealed an increase in viral Ag distribution in comparison with control (medium-infused) infected mice. Necrosis and inflammation paralleled the extent of viral Ag expression. Viral Ags were detected in discrete areas that usually remain uninfected in immunocompetent mice. These areas include the neocortex and caudate putamen nuclei, the piriform cortex, and the lateral olfactory tract. Neuronal loss and necrosis were consistently found in the olfactory bulb and the horizontal/vertical band of Broca. In some of the T-cell depleted mice, necrosis was also evident in the hippocampus, fimbria, mammillary bodies, and hypothalamic nuclei. In the brain stem, perivascular cuffing was evident, but with little necrosis. Collectively, these data suggest that CD4+ and CD8+ T cells make only a minor contribution to the development of histopathology but rather function together to limit viral replication and transsynaptic or ventricular spread of virus, thus promoting recovery. The primary effectors of histopathology appear to be related more to the cytopathologic nature of the virus infection and non-T-cell-mediated mechanisms.
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PMID:Central neuropathogenesis of vesicular stomatitis virus infection of immunodeficient mice. 810 6

Neuronal progenitor cells (NPC) are particularly suited as the target population for genetic and cellular therapy of neurological disorders such as Parkinson's disease or stroke. However, genetic modification of these cells using retroviral vectors remains a great challenge because of the low transduction rate and the need for fetal calf serum (FCS) during the transduction process that induces the cell differentiation to mature neurons. To overcome these problems, we developed a new retrovirus production system in which the simplified retroviral vector GCDNsap engineered to be resistant to denovo methylation was packaged in the vesicular stomatitis virus G protein (VSV-G), concentrated by centrifugation, and resuspended in serum-free medium (StemPro-34 SFM). In transduction experiments using enhanced green fluorescent protein (EGFP) as a marker, the concentrated FCS-free virus supernatant infected NPC at a high rate, while maintaining the ability of these cells to self-renew and differentiate in vitro. When such cells were grafted into mouse brains, EGFP-expressing NPC were detected in the region around the injection site at 8 weeks post transplantation. These findings suggest that the gene transfer system described here may provide a useful tool to genetically modify NPC for treatments of neurological disorders.
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PMID:Feasibility of ex vivo gene therapy for neurological disorders using the new retroviral vector GCDNsap packaged in the vesicular stomatitis virus G protein. 1235 1

We have produced high-titre HIV-1 green fluorescent protein-expressing lentiviral (LV) vectors pseudotyped with strain 3908 Venezuelan equine encephalitis virus glycoprotein (VEEV-G) and used them to study transduction of: (1) rat embryonic motor neuron (MN) and striatal neuron primary cultures, (2) differentiated MN cell line NSC-34 and (3) adult rat striatum. In primary neuronal cultures, transduction with VEEV-G-pseudotyped LV was more efficient and more neuronal than with vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped LV. In NSC-34 cells clear retrograde transport of VEEV-G vector particles was observed. In the striatum at the injection site, transduction with the VEEV-G vectors driven by cytomegalovirus or phosphoglycerate kinase promoters exhibited a distinct neuronal tropism with no microglial and only a minor astroglial component, superior to that obtained with VSV-G-pseudotyped LV, irrespective of the promoter used. Neuronal transduction efficiency increased over time. Distal to the injection site transduction of mitral cells in the olfactory bulb, thalamic neurons and dopaminergic neurons in the substantia nigra pars compacta was detected. This, together with observations of retrograde axonal trafficking in vitro indicates that these vectors also possess low level of retrograde neuronal transduction capability in vivo. In this study, we demonstrate both strong neurotropism as well as sustainability of expression and minimal host immune response in vivo, making the VEEV-G-pseudotyped LV vectors potentially useful for gene therapy of neurodegenerative diseases.
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PMID:Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors. 2317 19