Lack of nitric oxide synthase type 2 (NOS2) results in reduced neuronal apoptosis and mortality following mouse hepatitis virus infection of the central nervous system

Chen, Benjamin P.; Lane, Thomas E.

doi:10.1080/135502802317247820

Cited by 20 publications

(22 citation statements)

References 35 publications

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“…Theiler's murine encephalomyelitis virus (Rubio et al, 2003) and Sindbis virus (Kimura and Griffin, 2003) were also reported to induce apoptosis, with most of the infected cells not showing hallmarks of apoptosis, as we also observed following HCoV-OC43 infection. The murine counterpart of HCoV-OC43, MHV, was also reported to induce apoptosis in mouse brain (Chen and Lane, 2002;Wu and Perlman, 1999;Schwartz et al, 2002). Apoptosis induced by coronaviral infection could be associated with HCoV-mediated neuropathogenesis by killing cells or by disseminating virus while limiting inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

et al. 2006

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The notion that an infectious respiratory pathogen can damage the central nervous system (CNS) and lead to neurological disease was tested using a human respiratory coronavirus, the OC43 strain of human coronavirus (HCoV-OC43). First, primary cell cultures were used to determine the susceptibility of each type of neural cells to virus infection. Neurons were the target cells, undergoing degeneration during infection, in part due to apoptosis. Second, neuropathogenicity was investigated in susceptible mice. Intracerebral inoculation of HCoV-OC43 into BALB/c mice led to an acute encephalitis with neuronal cell death by necrosis and apoptosis. Infectious virus was apparently cleared from surviving animals, whereas viral RNA persisted for several months. Some of the animals surviving to acute encephalitis presented an abnormal limb clasping reflex and a decrease in motor activity starting several months post-infection. These results suggest that viral persistence could be associated with an increased neuronal degeneration leading to neuropathology and motor deficits in susceptible individuals.

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Section: Discussionmentioning

confidence: 99%

Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

et al. 2006

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“…In consequence, nitric oxide-derived oxidants are more likely to cause nonspecific nitro-oxidative damage in virusinfected tissue than to eliminate the virus [47][48][49]. Accordingly, it has been reported that infection of iNOS knockout (−/−) and iNOS (+/+) mice with MHV resulted in similar kinetics of virus clearance, but in reduced neuronal apoptosis and mortality [50]. We did not follow the kinetics of virus clearance in our experimental setting, but we did show that 7 days after infection, tempol reduced viral load, iNOS expression, and CNS damage.…”

Section: Discussionmentioning

confidence: 99%

Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation

Tsuhako

Augusto

Linares

et al. 2010

Free Radical Biology and Medicine

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Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating disease of the human central nervous system (CNS). Most of the knowledge about the pathogenesis of MS has been derived from murine models, such as experimental autoimmune encephalomyelitis and viral encephalomyelitis. Here, we infected female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV-59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing encephalomyelitis. In untreated animals, neurological symptoms developed quickly: 90% of infected mice died 10 days after virus inoculation and the few survivors presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses on the first day and daily doses for 7 days plus 2 mM tempol in the drinking water ad libitum) profoundly altered the disease outcome: neurological symptoms were attenuated, mouse survival increased up to 70%, and half of the survivors behaved as normal mice. Not surprisingly, tempol substantially preserved the integrity of the CNS, including the blood-brain barrier. Furthermore, treatment with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-alpha and interferon-gamma, and protein nitration. The results indicate that tempol ameliorates murine viral encephalomyelitis by altering the redox status of the infectious environment that contributes to an attenuated CNS inflammatory response. Overall, our study supports the development of therapeutic strategies based on nitroxides to manage neuroinflammatory diseases, including MS.

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“…HCoV-OC43 was previously reported to induce apoptosis in MRC-5 cells, a lung cell line 11 but not in infected human monocytes/macrophages, unlike the infection observed with strain 229E. 12 The murine counterpart of HCoV-OC43, MHV, was reported to induce apoptosis in 17Cl-1 cells, a murine fibroblast cell line 13 and in mouse brain neurons 14,15 in addition to macrophage/microglial cells, astrocytes and oligodendrocytes. 16,17 And recently, SARS-CoV was shown to induce apoptosis of Vero E6 cells.…”

Section: Discussionmentioning

confidence: 99%

HCoV-Oc43–Induced Apoptosis of Murine Neuronal Cells

Jacomy

Talbot

2006

Advances in Experimental Medicine and Biology

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Lack of nitric oxide synthase type 2 (NOS2) results in reduced neuronal apoptosis and mortality following mouse hepatitis virus infection of the central nervous system

Cited by 20 publications

References 35 publications

Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation

HCoV-Oc43–Induced Apoptosis of Murine Neuronal Cells

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