We ex the axonal transport of two strain of herpes simplex virus 1 (HSV-1) within the central nervous system ofcebus monkeys. Each strain was inijected into the "arm area" of the primry motor cortex. One strain, HSV-1(McIntyre-B), was transported transneuronaly in the retrograde direction. It infected neurons at sites known to project to the arm area of the primary motor cortex (e.g., ventrolateral thalamus). In addition-, "second-order" neurons were labeled in the deep cerebellar nuclei (dentate and interpositus) and in the globus pallidus (internal s ). This result supports the concept that the arm area of the primary motor cortex is a target of both cerebellar and basal ganglia output. In contrast, the other strain, HSV-1(H129), was transported transneuronally in the anterograde direction. It infected neurons at sites known to receive input from the arm area of the primary motor cortex (e.g., putamen, pontine nuclei). In addition, "third-order" neurons were labeled in the cerebellar cortex (granule and Golgi celis) and in the globus paldus (largely the external segment). Our observations suggest that strain differences have an important impact on the direction of transneuronal transport of HSV-1. Furthermore, it should be possible to examine the organization of cerebeflar and basal ganglia loops with cerebral-cortex by exploiting tusneuronal transport of HSV-1 and virus strain differences.Part .of the neural substrate for the central control of movement in primates is formed by multiple "loops" between the cerebral cortex and two subcortical centers, the basal ganglia and the cerebellum. These circuits are thought to be involved in many aspects of motor behavior, including the programming, initiation, and regulation of limb movement (e.g., refs. 1-4). In recent experiments, we have begun to explore the structure of these loops by using transneuronal transport of herpes simplex virus 1 (HSV-1). In the course of these studies, we made the surprising observation that the direction of transneuronal transport within these circuits depends on the specific strain of HSV-1 inoculated into the animal. To illustrate this result, in this report we describe some of the patterns of transneuronal-transport of two strains of HSV-1 within the pathways that link the "arm area" of the primary motor cortex with the basal ganglia and cerebellum. MATERIALS AND METHODSEither the H129 strain (5) (1.5 x 1012 plaque-forming units (pfu)/ml, n = 2; 8.0 x 1010 pfu/ml, n = 1) or the McIntyre-B strain (6) (6.1 x 10P pfu/ml, n = 2) ofHSV-1 was injected into the left arm area of the primary motor cortex (7) of cebus monkeys (Cebus apella). Each animal was anesthetized with ketamine (10 mg/kg, i.m.) and Nembutal (sodium pentobarbital, 25 mg/kg, i.p.), and 0.05 jul of virus was injected at each of six cortical sites. The surgical procedures used have been described in detail (8,9). The injection sites included both the crest of the precentral gyrus and the anterior bank of the central sulcus. Two to three days after inoculation, anima...
Although various methods of immunosuppression have been used to enhance susceptibility of mice to murine cytomegalovirus (MCMV) retinitis, none reproduce the unique complexity of immune deficiency experienced by patients during the progression of AIDS. C57BL/6 mice are susceptible to a retrovirus-induced murine acquired immune deficiency syndrome (MAIDS), characterized by progressive immune dysfunction which shares many features with AIDS. We therefore evaluated the frequency and severity of MCMV retinitis in C57BL/6 mice with MAIDS. Following subretinal inoculation of MCMV, nearly 90% of mice with MAIDS developed a necrotizing retinitis 8 to 10 days postinfection, whereas retinitis was observed in only 8% of age-matched immunocompetent control mice. Histopathologic analysis of the retinitis that developed in mice with MAIDS revealed features similar to those found in AIDS-related CMV retinitis. Eyes from MAIDS animals also contained on average higher amounts of infectious virus when compared with eyes from control animals. We conclude that retrovirus-induced immunosuppression increases susceptibility of C57BL/6 mice to MCMV retinitis.
Twenty-three strains of herpes simplex virus type 1 were compared for their pathogenicity in 4-week-old BALB/c mice after peripheral (footpad) or intracerebral inoculation. Among those strains examined were (i) six clinical isolates of brain or cerebrospinal fluid origin, (ii) seven clinical isolates of oral or genital origin, (iii) five prototype laboratory strains that have been passaged numerous times in culture, and (iv) five syncytial variants capable of producing cell fusion in
Monoclonal antibodies HC1 and HD1, directed against herpes simplex virus type 1 (HSV-1) glycoproteins gC and gD, respectively, were evaluated for their ability to passively immunize mice against acute virus-induced neurological disease after footpad inoculation with HSV-1 or herpes simplex virus type 2 (HSV-2). Control virus-infected mice receiving a single intraperitoneal injection of normal serum died within 7 to 10 days after the spread of virus from footpad to spinal cord and brain. However, a single intraperitoneal injection of either HC1 or HD1 antibody protected mice from neurological illness and death when administered to HSV-1 (strain HTZ)-infected mice at either 2 h before virus challenge or at 24 h after virus inoculation. To determine the in vivo specificity of the antibodies, passive transfer studies were performed with mice infected with the MP strain of HSV-1, a mutant of HSV-1 (mP) which is defective in the production of glycoprotein gC. Whereas HD1 antibody decreased the incidence of neurological illness in MP-and mP-infected mice, HC1 antibody, which protected mP-infected animals, failed to protect mice infected with the MP strain. When HD1 antibody was administered to HSV-2 (strain G)-infected mice at either 2 h before virus challenge or at 6 h (but not 24 h) after virus inoculation, 100% of the infected animals receiving HD1 antibody survived. In contrast, 100% of HSV-2 (strain G)-infected animals passively immunized with HC1 antibody developed neurological illness and died. These results provide in vivo evidence that the HSV-induced glycoprotein gC expresses type-specific antigenic determinants, whereas glycoprotein gD expresses type-common determinants.
AIDS-related human cytomegalovirus (HCMV) retinitis remains a major ophthalmologic problem worldwide. Although this sight-threatening disease is well characterized clinically, many pathogenic issues remain unresolved, among them a basic understanding of the relative roles of cell death pathways during development of retinal tissue destruction. Using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS), we initially investigated MCMV-infected eyes for evidence of apoptosis-associated molecules in mice with MAIDS of 4 weeks' (MAIDS-4) and 10 weeks' (MAIDS-10) duration, which were resistant and susceptible to retinal disease, respectively, but which harbored equivalent amounts of infectious MCMV. Whereas MCMV-infected eyes of MAIDS-4 mice showed little evidence of apoptosis-associated molecules, MCMV-infected eyes of MAIDS-10 mice showed significant amounts of tumor necrosis factor alpha (TNF-α), TNF receptors 1 and 2, active caspase 8, active caspase 3, TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-R(DR5), Fas, and Fas ligand mRNAs and/or proteins, all detected at peak amounts prior to development of most severe retinal disease. Immunohistochemical staining showed macrophages, granulocytes (neutrophils), Müller cells, and microglial cells as TNF-α sources. Remarkably, quantification of apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay suggested that apoptosis contributed minimally to retinal disease in MCMV-infected eyes of MAIDS-10 mice. Subsequent studies demonstrated that MCMV-infected eyes of MAIDS-10 mice, but not MAIDS-4 mice, showed evidence of significant increases in molecules associated with two additional cell death pathways, necroptosis (receptor-interacting protein 1 [RIP1] and RIP3 mRNAs) and pyroptosis (caspase 1, interleukin 1β [IL-1β], and IL-18 mRNAs). We conclude that apoptosis, necroptosis, and pyroptosis participate simultaneously during MAIDS-related MCMV retinitis, and all may play a role during AIDS-related HCMV retinitis.
Herpes simplex virus 1 (HSV-1) is a widespread global pathogen, of which the strain KOS is one of the most extensively studied. Previous sequence studies revealed that KOS does not cluster with other strains of North American geographic origin, but instead clustered with Asian strains. We sequenced a historical isolate of the original KOS strain, called KOS63, along with a separately isolated strain attributed to the same source individual, termed KOS79. Genomic analyses revealed that KOS63 closely resembled other recently sequenced isolates of KOS and was of Asian origin, but that KOS79 was a genetically unrelated strain that clustered in genetic distance analyses with HSV-1 strains of North American/European origin. These data suggest that the human source of KOS63 and KOS79 could have been infected with two genetically unrelated strains of disparate geographic origins. A PCR RFLP test was developed for rapid identification of these strains.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.