Interferon-γ induced type I nitric oxide synthase activity inhibits viral replication in neurons

Komatsu, Takashi; Bi, Zhengbiao; Reiss, Carol Shoshkes

doi:10.1016/0165-5728(96)00083-5

Cited by 132 publications

(108 citation statements)

References 34 publications

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“…Antibodies seem to play a prominent role in the case of neuronal infection with Theiler's murine encephalitis virus (19), the neurotropic JHM variant of mouse hepatitis virus (17), Sindbis virus (8,37), and rabies virus (51). A contribution of IFN-␥ in viral clearance from neurons has previously been noted in a number of neurotropic virus infections, including vaccinia virus and vesicular stomatitis virus (35,36), measles virus (49,69), neurotropic mouse hepatitis virus (7,48,50), Sindbis virus (8), and lymphocytic choriomeningitis virus (65). However, the strict and exclusive dependence of BDV resistance on IFN-␥ during primary and secondary immune responses is unique.…”

Section: Discussionmentioning

confidence: 99%

“…The induction of NO synthase in macrophages, microglia, or neurons (30) and the subsequent synthesis of nitric oxide could contribute to the antiviral activity of IFN-␥ toward BDV. Nitric oxide is involved in the elimination of vesicular stomatitis virus from the CNS of mice (35). MRL mice with a defective NOS-2 gene showed a slightly enhanced rate of neurological disease after neonatal infection with BDV compared to NOS-2-expressing littermates (28), suggesting that IFN-␥-induced synthesis of nitric oxide could indeed play a role in the resistance of mice to BDV.…”

Section: Vol 79 2005 Ifn-␥ Mediates Borna Disease Virus Clearance Fmentioning

confidence: 99%

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CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-␥) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-␥-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-␥-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-␥-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-␥ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-␥ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

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Section: Discussionmentioning

confidence: 99%

Section: Vol 79 2005 Ifn-␥ Mediates Borna Disease Virus Clearance Fmentioning

confidence: 99%

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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“…NB41A3 cells, a neuroblastoma cell line, have been shown to have many properties of neurons, including the ability to form neurotubules and neurofilaments and in the storage and release of catecholamines (Breakfield et al, 1975;Schubert et al, 1969); they constitutively express neuronal nitric oxide synthase (NOS-1), IFN-γ eceptor (IFN-γ R), interleukin-12 receptor (IL-12R), and the N-methyl-D-aspartate (NMDA) receptor Ireland and Reiss, 2004;Komatsu et al, 1996). The effects of type I and II IFN on these cells have also been studied; the inhibitory effects of these cytokines on VSV replication are similar in these cells and in primary murine neurons (Chesler et al, 2003;Trottier et al, 2005).…”

Section: Vsv Does Not Induce Type I Ifn In Infected Neuroblastoma Cellsmentioning

confidence: 99%

Peripheral, but not central nervous system, type I interferon expression in mice in response to intranasal vesicular stomatitis virus infection

2007

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Type I interferon (IFN) is critical for resistance of mice to infection with vesicular stomatitis virus (VSV). Wild type (wt) VSV infection did not induce type I IFN production in vitro or in the central nervous system (CNS) of mice; however IFN-β was detected in lungs, spleen, and serum within 24 h. The M protein mutant VSV, T1026R1 (also referred to as M51R), induced type I IFN production in vitro and in the CNS, with poor expression in spleens. In addition, VSV T1026R1 was not pathogenic to mice after intranasal infection, illustrating the importance of IFN in controlling VSV replication in the CNS. Experiments with chemical sympathectomy, sRAGE, and neutralizing antibody to VSV were performed to investigate the mechanism(s) utilized for induction of peripheral IFN; neither sRAGE infusion nor chemical sympathectomy had an effect on peripheral IFN production. In contrast, administration of neutralizing antibody (Ab) readily blocked the response. Infectious VSV was transiently present in lungs and spleens at 24 h post infection. The results are consistent with VSV traffic from the olfactory neuroepithelium to peripheral lymphoid organs hematogenously or via lymphatic circulation. These results suggest that VSV replicates to high titers in the brains of mice because of the lack of IFN production in the CNS after intranasal VSV infection. In contrast, replication of VSV in peripheral organs is controlled by the production of large amounts of IFN.Address correpondence to

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“…40 An IFN-␥-dependent immune response further increases the local accumulation of activated immune cells and mediates the tissue damage of the CNS. [41][42][43][44] Phenotypically, these GF-IL12 transgenic mice develop a severe cerebellitis and, correspondingly, progressive ataxia. 25 However, most GF-IL12/CXCR3KO mice did not develop a clinical phenotype and had only minor histopathologic alterations of the cerebellum.…”

Section: Discussionmentioning

confidence: 99%

Opposing Roles for CXCR3 Signaling in Central Nervous System Versus Ocular Inflammation Mediated by the Astrocyte-Targeted Production of IL-12

Krauthausen

Ellis

Zimmermann

et al. 2011

The American Journal of Pathology

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Interferon-γ induced type I nitric oxide synthase activity inhibits viral replication in neurons

Cited by 132 publications

References 34 publications

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Peripheral, but not central nervous system, type I interferon expression in mice in response to intranasal vesicular stomatitis virus infection

Opposing Roles for CXCR3 Signaling in Central Nervous System Versus Ocular Inflammation Mediated by the Astrocyte-Targeted Production of IL-12

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