The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Ann M Arvin - One of the best experts on this subject based on the ideXlab platform.
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current in vivo models of varicella zoster virus Neurotropism
Viruses, 2019Co-Authors: Ravi Mahalingam, Leigh Zerboni, Ann M Arvin, Anne A Gershon, Michael D Gershon, Jeffrey I Cohen, Wayne L Gray, Ilhem Messaoudi, Vicki TrainadorgeAbstract:Varicella-zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. An understanding of VZV Neurotropism in humans has long been hampered by the lack of an adequate animal model. For example, experimental inoculation of VZV in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. The severe combined immune deficient human (SCID-hu) model allows the study of VZV Neurotropism for human neural sub-populations. Simian varicella virus (SVV) infection of rhesus macaques (RM) closely resembles both human primary VZV infection and reactivation, with analyses at early times after infection providing valuable information about the extent of viral replication and the host immune responses. Indeed, a critical role for CD4 T-cell immunity during acute SVV infection as well as reactivation has emerged based on studies using RM. Herein we discuss the results of efforts from different groups to establish an animal model of VZV Neurotropism.
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the pathogenesis of varicella zoster virus Neurotropism and infection
2016Co-Authors: Leigh Zerboni, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is both a neurotropic and lymphotropic human alphaherpesvirus that causes varicella, which is commonly known as chickenpox, as the primary infection in susceptible individuals. During primary infection, VZV gains access to sensory ganglia of the peripheral nervous system and establishes latency within neurons. VZV reactivation from latency causes herpes zoster, called “shingles,” and is associated with a vesicular rash localized to one of the cutaneous dermatomes. While the clinical manifestations of varicella and herpes zoster are well documented, knowledge about the mechanisms of VZV pathogenesis in the human host is limited because infections are rarely fatal and VZV is highly species-specific for the human host. VZV infection of human (hu) dorsal root ganglia (DRG), skin, and thymus/liver (T cell) xenografts in the severe combined immunodeficiency (SCID) mouse model has provided a system for investigating molecular mechanisms of VZV pathogenesis. SCIDhu xenografts are infected with recombinant VZV mutant viruses that have targeted deletions or mutations of specific genes or their promoters, which enables the assessment of functions of VZV protein subdomains during VZV replication in intact human tissues in vivo. Use of these models has provided opportunities to examine VZV neuropathobiology and has shown the importance of intrinsic and innate responses that modulate VZV infection in vivo and in the absence of an adaptive immune response, which SCID mice lack. Using these tools to investigate VZV pathogenesis has provided insight into the clinical manifestations of varicella, herpes zoster and VZV-associated neurologic sequelae.
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investigation of varicella zoster virus Neurotropism and neurovirulence using scid mouse human drg xenografts
Journal of NeuroVirology, 2011Co-Authors: Leigh Zerboni, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus. Investigating pathogenic mechanisms that contribute to VZV neurovirulence are made difficult by a marked host restriction. Our approach to investigating VZV Neurotropism and neurovirulence has been to develop a mouse–human xenograft model in which human dorsal root ganglia (DRG) are maintained in severe compromised immunodeficient (SCID) mice. In this review, we will describe our key findings using this model in which we have demonstrated that VZV infection of SCID DRG xenograft results in rapid and efficient spread, enabled by satellite cell infection and polykaryon formation, which facilitates robust viral replication and release of infectious virus. In neurons that persist following this acute replicative phase, VZV genomes are present at low frequency with limited gene transcription and no protein synthesis, a state that resembles VZV latency in the natural human host. VZV glycoprotein I and interaction between glycoprotein I and glycoprotein E are critical for neurovirulence. Our work demonstrates that the DRG model can reveal characteristics about VZV replication and long-term persistence of latent VZV genomes in human neuronal tissues, in vivo, in an experimental system that may contribute to our knowledge of VZV neuropathogenesis.
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Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV Neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV Neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate Neurotropism and neurovirulence. The SCID mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
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varicella zoster virus Neurotropism in scid mouse human dorsal root ganglia xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV Neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV Neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate Neurotropism and neurovirulence. The SCID mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
Leigh Zerboni - One of the best experts on this subject based on the ideXlab platform.
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current in vivo models of varicella zoster virus Neurotropism
Viruses, 2019Co-Authors: Ravi Mahalingam, Leigh Zerboni, Ann M Arvin, Anne A Gershon, Michael D Gershon, Jeffrey I Cohen, Wayne L Gray, Ilhem Messaoudi, Vicki TrainadorgeAbstract:Varicella-zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. An understanding of VZV Neurotropism in humans has long been hampered by the lack of an adequate animal model. For example, experimental inoculation of VZV in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. The severe combined immune deficient human (SCID-hu) model allows the study of VZV Neurotropism for human neural sub-populations. Simian varicella virus (SVV) infection of rhesus macaques (RM) closely resembles both human primary VZV infection and reactivation, with analyses at early times after infection providing valuable information about the extent of viral replication and the host immune responses. Indeed, a critical role for CD4 T-cell immunity during acute SVV infection as well as reactivation has emerged based on studies using RM. Herein we discuss the results of efforts from different groups to establish an animal model of VZV Neurotropism.
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the pathogenesis of varicella zoster virus Neurotropism and infection
2016Co-Authors: Leigh Zerboni, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is both a neurotropic and lymphotropic human alphaherpesvirus that causes varicella, which is commonly known as chickenpox, as the primary infection in susceptible individuals. During primary infection, VZV gains access to sensory ganglia of the peripheral nervous system and establishes latency within neurons. VZV reactivation from latency causes herpes zoster, called “shingles,” and is associated with a vesicular rash localized to one of the cutaneous dermatomes. While the clinical manifestations of varicella and herpes zoster are well documented, knowledge about the mechanisms of VZV pathogenesis in the human host is limited because infections are rarely fatal and VZV is highly species-specific for the human host. VZV infection of human (hu) dorsal root ganglia (DRG), skin, and thymus/liver (T cell) xenografts in the severe combined immunodeficiency (SCID) mouse model has provided a system for investigating molecular mechanisms of VZV pathogenesis. SCIDhu xenografts are infected with recombinant VZV mutant viruses that have targeted deletions or mutations of specific genes or their promoters, which enables the assessment of functions of VZV protein subdomains during VZV replication in intact human tissues in vivo. Use of these models has provided opportunities to examine VZV neuropathobiology and has shown the importance of intrinsic and innate responses that modulate VZV infection in vivo and in the absence of an adaptive immune response, which SCID mice lack. Using these tools to investigate VZV pathogenesis has provided insight into the clinical manifestations of varicella, herpes zoster and VZV-associated neurologic sequelae.
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investigation of varicella zoster virus Neurotropism and neurovirulence using scid mouse human drg xenografts
Journal of NeuroVirology, 2011Co-Authors: Leigh Zerboni, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a medically important human alphaherpesvirus. Investigating pathogenic mechanisms that contribute to VZV neurovirulence are made difficult by a marked host restriction. Our approach to investigating VZV Neurotropism and neurovirulence has been to develop a mouse–human xenograft model in which human dorsal root ganglia (DRG) are maintained in severe compromised immunodeficient (SCID) mice. In this review, we will describe our key findings using this model in which we have demonstrated that VZV infection of SCID DRG xenograft results in rapid and efficient spread, enabled by satellite cell infection and polykaryon formation, which facilitates robust viral replication and release of infectious virus. In neurons that persist following this acute replicative phase, VZV genomes are present at low frequency with limited gene transcription and no protein synthesis, a state that resembles VZV latency in the natural human host. VZV glycoprotein I and interaction between glycoprotein I and glycoprotein E are critical for neurovirulence. Our work demonstrates that the DRG model can reveal characteristics about VZV replication and long-term persistence of latent VZV genomes in human neuronal tissues, in vivo, in an experimental system that may contribute to our knowledge of VZV neuropathogenesis.
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Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV Neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV Neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate Neurotropism and neurovirulence. The SCID mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
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varicella zoster virus Neurotropism in scid mouse human dorsal root ganglia xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV Neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV Neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate Neurotropism and neurovirulence. The SCID mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
Jeffrey I Cohen - One of the best experts on this subject based on the ideXlab platform.
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current in vivo models of varicella zoster virus Neurotropism
Viruses, 2019Co-Authors: Ravi Mahalingam, Leigh Zerboni, Ann M Arvin, Anne A Gershon, Michael D Gershon, Jeffrey I Cohen, Wayne L Gray, Ilhem Messaoudi, Vicki TrainadorgeAbstract:Varicella-zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. An understanding of VZV Neurotropism in humans has long been hampered by the lack of an adequate animal model. For example, experimental inoculation of VZV in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. The severe combined immune deficient human (SCID-hu) model allows the study of VZV Neurotropism for human neural sub-populations. Simian varicella virus (SVV) infection of rhesus macaques (RM) closely resembles both human primary VZV infection and reactivation, with analyses at early times after infection providing valuable information about the extent of viral replication and the host immune responses. Indeed, a critical role for CD4 T-cell immunity during acute SVV infection as well as reactivation has emerged based on studies using RM. Herein we discuss the results of efforts from different groups to establish an animal model of VZV Neurotropism.
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rodent models of varicella zoster virus Neurotropism
Current Topics in Microbiology and Immunology, 2010Co-Authors: Jeffrey I CohenAbstract:Inoculation of rodents with varicella-zoster virus (VZV) results in a latent infection in dorsal root ganglia with expression of at least five of the six VZV transcripts and one of the viral proteins that are reported to be expressed during latency in human ganglia. Rats develop allodynia and hyperalgesia in the limb distal to the site of injection and the resulting exaggerated withdrawal response to stimuli is reduced by treatment with gabapentin and amitryptyline, but not by antiviral therapy. Inoculation of rats with VZV mutants show that most viral genes are dispensable for latency, but that some genes (e.g., ORF4, 29, and ORF63) that are expressed during latency are important for the establishment of latency in rodents, but not for infection of rodent ganglia. The rodent model for VZV latency allows one to study ganglia removed immediately after death, avoiding the possibility of reactivation, and helps to identify VZV genes required for latency.
Christopher Power - One of the best experts on this subject based on the ideXlab platform.
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lentiviral neuropathogenesis comparative neuroinvasion Neurotropism neurovirulence and host neurosusceptibility
Journal of Virology, 2002Co-Authors: Megan K Patrick, James B Johnston, Christopher PowerAbstract:Despite extensive genetic diversity among lentiviruses, they share many biological properties, including similar structural and genomic organizations, Mg2+-dependent reverse transcriptase activity, and broad cellular tropisms involving both proliferating and nonproliferating cells within and outside the nervous system (30). Lentiviruses can also be subdivided on the basis of pathogenesis into peripheral immune deficiency-inducing viruses, such as human (HIV), simian (SIV), feline (FIV), bovine (BIV), and chimeric simian-human (SHIV) immunodeficiency viruses, and those that are immune activators, including caprine arthritis encephalitis virus (CAEV), maedi-visna virus (MVV), and equine infectious anemia virus (EIAV) (Table (Table1).1). Systemically, most lentiviruses exhibit a distinct disease pattern in which primary infection induces acute disease and an intense immune response, followed by a lengthy period of subclinical infection (lenti = slow) and a terminal phase resulting in death (22). Immunodeficiency-associated lentiviral infections usually trigger a robust host immune response that is diminished over time, permitting opportunistic infections. In contrast, infections by the immune-activating lentiviruses are characterized by a terminal phase of host immune activation. CAEV and MVV infections are manifested as systemic inflammation with chronic arthritis, pneumonia, and mastitis, while EIAV induces recurrent episodes of an autoimmune-mediated acute hemolytic disease (17, 57, 89).
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distinct hiv 1 env sequences are associated with Neurotropism and neurovirulence
Current Topics in Microbiology and Immunology, 1995Co-Authors: Christopher Power, Justin C Mcarthur, Richard T Johnson, Diane E Griffin, Jonathan D Glass, R Dewey, Bruce ChesebroAbstract:Retroviral infections in many species are commonly associated with different forms of neurological illness. These neurological diseases differ widely in their clinical manifestations and in the extent of pathological changes such as severity of inflammation and sites of tissue destruction in the nervous system. For example, the human oncovirus HTLV-1 causes a myelopathy in less than 1% of infected adults (Roman 1988). Spinal cord pathology shows intense inflammation with T cell infiltrates and minimal virus detectable within the lesions (Power et al. 1991; Roman 1988). The type C murine retroviruses can induce a variety of CNS diseases. Cas Br E (Lynch et al. 1991; Gardner et al. 1973; Jolicoeur et al. 1992a), Friend PVC 211 (Masuda et al. 1992, 1993), and Moloney-ts 1 murine leukemia viruses (Szurek et al. 1990) cause a disease with spastic paralysis associated with noninflammatory spongiform degeneration involving primarily the gray matter of the spinal cord and brain stem. In contrast, FMCF-98D murine retrovirus (Buller et al. 1990) causes an ataxic disease associated with infection of white matter tracts of the cerebellum but showing minimal pathology. Friend TR 1.3 induces a stroke-like syndrome secondary to infection of brain capillary endothelial cells (Park et al. 1993). The lentiviruses including visna, CAEV, SIV, FIV, and HIV also cause a number of differing clinical syndromes with variable pathology. SIV, CAEV, and visna may be characterized by a progressive downhill neurological course of varying rapidity accompanied by widespread inflammation of the CNS (Sharma et al. 1992; Georgsson et al. 1989; Lackner et al. 1991; Narayan and Clements 1989).
Vicki Trainadorge - One of the best experts on this subject based on the ideXlab platform.
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current in vivo models of varicella zoster virus Neurotropism
Viruses, 2019Co-Authors: Ravi Mahalingam, Leigh Zerboni, Ann M Arvin, Anne A Gershon, Michael D Gershon, Jeffrey I Cohen, Wayne L Gray, Ilhem Messaoudi, Vicki TrainadorgeAbstract:Varicella-zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. An understanding of VZV Neurotropism in humans has long been hampered by the lack of an adequate animal model. For example, experimental inoculation of VZV in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. The severe combined immune deficient human (SCID-hu) model allows the study of VZV Neurotropism for human neural sub-populations. Simian varicella virus (SVV) infection of rhesus macaques (RM) closely resembles both human primary VZV infection and reactivation, with analyses at early times after infection providing valuable information about the extent of viral replication and the host immune responses. Indeed, a critical role for CD4 T-cell immunity during acute SVV infection as well as reactivation has emerged based on studies using RM. Herein we discuss the results of efforts from different groups to establish an animal model of VZV Neurotropism.