The Experts below are selected from a list of 21822 Experts worldwide ranked by ideXlab platform
Donald H Gilden - One of the best experts on this subject based on the ideXlab platform.
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neurological complications of varicella zoster Virus Reactivation
Current Opinion in Neurology, 2014Co-Authors: M Nagel, Donald H GildenAbstract:Purpose of review Varicella zoster Virus (VZV) Reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis, and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes, and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV Reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed. Recent findings After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephalitis, myelitis, and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in cerebrospinal fluid and treated with intravenous acyclovir. Summary Awareness of the expanding spectrum of neurological complications caused by VZV Reactivation with and without rash will improve diagnosis and treatment.
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t cells increase before zoster and pd 1 expression increases at the time of zoster in immunosuppressed nonhuman primates latently infected with simian varicella Virus
Journal of NeuroVirology, 2014Co-Authors: Stephanie James, Vicki Trainadorge, Donald H Gilden, Eileen Deharo, Brent E Palmer, Ravi MahalingamAbstract:Like varicella zoster Virus in humans, simian varicella Virus (SVV) becomes latent in ganglionic neurons along the entire neuraxis and reactivates in immunosuppressed monkeys. Five rhesus macaques were inoculated with SVV; 142 days later (latency), four monkeys were immunosuppressed, and T cells were analyzed for naive, memory, and effector phenotypes and expression of programmed death receptor-1 (PD-1; T cell exhaustion). All T cell subsets decreased during immunosuppression and except for CD8 effectors, peaked 2 weeks before zoster. Compared to before immunosuppression, PD-1 expression increased at Reactivation. Increased T cells before zoster is likely due to Virus Reactivation.
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simian varicella Virus pathogenesis
Current Topics in Microbiology and Immunology, 2010Co-Authors: Ravi Mahalingam, Ilhem Messaoudi, Donald H GildenAbstract:Because varicella zoster Virus (VZV) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and Reactivation. The pathological, virological, and immunological features of simian varicella Virus (SVV) infection in nonhuman primates are similar to those of VZV infection in humans. Both natural infection of cynomolgus and African green monkeys as well as intrabronchial inoculation of rhesus macaques with SVV provide the most useful models to study viral and immunological aspects of latency and the host immune response. Experimental immunosuppression of monkeys latently infected with SVV results in zoster, thus providing a new model system to study how the loss of adaptive immunity modulates Virus Reactivation.
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neurological disease produced by varicella zoster Virus Reactivation without rash
Current Topics in Microbiology and Immunology, 2010Co-Authors: Donald H Gilden, Ravi Mahalingam, Randall J Cohrs, M NagelAbstract:Reactivation of varicella zoster Virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitis, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy, myelopathy, and various inflammatory disorders of the eye. Importantly, VZV Reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions varies from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum.
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simian varicella Virus Reactivation in cynomolgus monkeys
Virology, 2007Co-Authors: Ravi Mahalingam, Vicki Trainadorge, Elizabeth Brazeau, Robert Sanford, Erin P Ribka, Rebecca Lorino, Scott J Alleman, Donald H GildenAbstract:SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella Reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical Reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical Reactivation. Virus Reactivation was confirmed not only by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.
Ravi Mahalingam - One of the best experts on this subject based on the ideXlab platform.
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t cells increase before zoster and pd 1 expression increases at the time of zoster in immunosuppressed nonhuman primates latently infected with simian varicella Virus
Journal of NeuroVirology, 2014Co-Authors: Stephanie James, Vicki Trainadorge, Donald H Gilden, Eileen Deharo, Brent E Palmer, Ravi MahalingamAbstract:Like varicella zoster Virus in humans, simian varicella Virus (SVV) becomes latent in ganglionic neurons along the entire neuraxis and reactivates in immunosuppressed monkeys. Five rhesus macaques were inoculated with SVV; 142 days later (latency), four monkeys were immunosuppressed, and T cells were analyzed for naive, memory, and effector phenotypes and expression of programmed death receptor-1 (PD-1; T cell exhaustion). All T cell subsets decreased during immunosuppression and except for CD8 effectors, peaked 2 weeks before zoster. Compared to before immunosuppression, PD-1 expression increased at Reactivation. Increased T cells before zoster is likely due to Virus Reactivation.
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simian varicella Virus pathogenesis
Current Topics in Microbiology and Immunology, 2010Co-Authors: Ravi Mahalingam, Ilhem Messaoudi, Donald H GildenAbstract:Because varicella zoster Virus (VZV) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and Reactivation. The pathological, virological, and immunological features of simian varicella Virus (SVV) infection in nonhuman primates are similar to those of VZV infection in humans. Both natural infection of cynomolgus and African green monkeys as well as intrabronchial inoculation of rhesus macaques with SVV provide the most useful models to study viral and immunological aspects of latency and the host immune response. Experimental immunosuppression of monkeys latently infected with SVV results in zoster, thus providing a new model system to study how the loss of adaptive immunity modulates Virus Reactivation.
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neurological disease produced by varicella zoster Virus Reactivation without rash
Current Topics in Microbiology and Immunology, 2010Co-Authors: Donald H Gilden, Ravi Mahalingam, Randall J Cohrs, M NagelAbstract:Reactivation of varicella zoster Virus (VZV) from latently infected human ganglia usually produces herpes zoster (shingles), characterized by dermatomal distribution pain and rash. Zoster is often followed by chronic pain (postherpetic neuralgia or PHN) as well as meningitis or meningoencephalitis, cerebellitis, isolated cranial nerve palsies that produce ophthalmoplegia or the Ramsay Hunt syndrome, multiple cranial nerve palsies (polyneuritis cranialis), vasculopathy, myelopathy, and various inflammatory disorders of the eye. Importantly, VZV Reactivation can produce chronic radicular pain without rash (zoster sine herpete), as well as all the neurological disorders listed above without rash. The protean neurological and ocular disorders produced by VZV in the absence of rash are a challenge to the practicing clinician. The presentation of these conditions varies from acute to subacute to chronic. Virological confirmation requires the demonstration of amplifiable VZV DNA in cerebrospinal fluid (CSF) or in blood mononuclear cells, or the presence of anti-VZV IgG antibody in CSF or of anti-VZV IgM antibody in CSF or serum.
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simian varicella Virus Reactivation in cynomolgus monkeys
Virology, 2007Co-Authors: Ravi Mahalingam, Vicki Trainadorge, Elizabeth Brazeau, Robert Sanford, Erin P Ribka, Rebecca Lorino, Scott J Alleman, Donald H GildenAbstract:SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella Reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical Reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical Reactivation. Virus Reactivation was confirmed not only by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.
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disseminated simian varicella Virus infection in an irradiated rhesus macaque macaca mulatta
Journal of Virology, 2007Co-Authors: Krishnan Kolappaswamy, Ravi Mahalingam, Vicki Trainadorge, Donald H Gilden, Steven T Shipley, B K Kleinschmidtdemasters, Charles G Mcleod, Laura L Hungerford, Louis J DetollaAbstract:We describe correlative clinicopathological/virological findings from a simian varicella Virus (SVV)-seronegative monkey that developed disseminated varicella 105 days after gamma-irradiation. Twelve other monkeys in the colony were also irradiated, none of which developed varicella. Before irradiation, sera from the monkey that developed disseminated infection and one asymptomatic monkey were available. Analysis indicated that subclinical Reactivation of latent SVV from an asymptomatic irradiated monkey likely led to disseminated varicella in the seronegative irradiated monkey. These findings parallel those from humans with disseminated varicella infection and support the usefulness of SVV infection as a model for human varicella-zoster Virus infection, particularly Virus Reactivation after gamma-irradiation.
Robert F Siliciano - One of the best experts on this subject based on the ideXlab platform.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
Hungchih Yang - One of the best experts on this subject based on the ideXlab platform.
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hepatitis b Virus Reactivation in patients receiving interferon free direct acting antiviral agents for chronic hepatitis c Virus infection
Open Forum Infectious Diseases, 2017Co-Authors: Chenhua Liu, Chunjen Liu, Yujen Fang, Hungchih Yang, Peijer Chen, Dingshinn Chen, Jiahorng KaoAbstract:BACKGROUND Little is known about the risk of hepatitis B Virus (HBV) Reactivation in patients receiving interferon (IFN)-free direct-acting antiviral agents (DAAs) for hepatitis C Virus (HCV). METHODS Patients who were seropositive for HBV core antibody and who received IFN-free DAAs for HCV were enrolled. Hepatitis B Virus Reactivation was defined as reappearance of serum HBV deoxyribonucleic acid (DNA) ≥100 IU/mL in patients with baseline undetectable viral load, or ≥2 log10 IU/mL increase of HBV DNA in patients with baseline detectable viral load. Hepatitis B Virus-related alanine aminotransferase (ALT) flare was defined as ALT ≥5 times upper limit of normal or ≥2 times of the baseline level. Hepatitis B Virus-related hepatic decompensation was defined as presence of jaundice, coagulopathy, hepatic encephalopathy, or ascites. RESULTS Compared with no HBV Reactivation in 81 HBV surface antigen (HBsAg)-negative patients, 2 of 12 HBsAg-positive patients had HBV Reactivation (0% [confidence interval {95% CI}, 0%-4.5%] vs 16.7% [95% CI, 4.7%-44.8%], P = .015). No patients had ALT flare or hepatic decompensation. Baseline HBsAg level at a cutoff value of 500 IU/mL was associated with HBV Reactivation in HBsAg-positive patients. There was no HBsAg seroreversion in HBsAg-negative patients. CONCLUSIONS Hepatitis B Virus Reactivation is limited to HBsAg-positive patients receiving IFN-free DAAs for HCV. Higher baseline HBsAg levels are associated with HBV Reactivation. The risk of ALT flares or hepatic decompensation is low in these patients.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
Liang Shan - One of the best experts on this subject based on the ideXlab platform.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
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stimulation of hiv 1 specific cytolytic t lymphocytes facilitates elimination of latent viral reservoir after Virus Reactivation
Immunity, 2012Co-Authors: Liang Shan, Hungchih Yang, Kai Deng, Neeta S Shroff, Christine M Durand, Alireza S Rabi, Hao Zhang, Joseph Bernard Margolick, Joel N Blankson, Robert F SilicianoAbstract:Summary Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the Virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proViruses without inducing global T cell activation. However, the killing of the infected cells after Virus Reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4 + T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials.
