Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection

Shrestha, Bimmi; Wang, Tian; Samuel, Melanie A.; Whitby, Kevin; Craft, Joe; Fikrig, Erol; Diamond, Michael S.

doi:10.1128/jvi.00274-06

Cited by 178 publications

(157 citation statements)

References 74 publications

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“…The residential glial cells in the brain are activated in response to IFN-γ, and express a variety of PRRs that are involved in recognition of apoptotic-associated molecular patterns on the surface of apoptotic cells. Although IFN-γ participated in the clearance of Sindbis virus, a mosquito-borne alphavirus, from infected neurons [219], it was dispensable for clearance of WNV from CNS [137]. Collectively, these observations suggest that type I IFN signaling directly modulates viral replication in CNS tissues, and that IFN-γ is indirectly involved in clearance of apoptotic cells from the CNS.…”

Section: Innate Immune Response To Arboviruses In the Cnsmentioning

confidence: 72%

“…Hence, inhibition of CXCR4 results in enhanced entry of CD8 T cells into the CNS and improves mice survival from lethal WNV infection [233]. Further, mice deficient in CD8 T cells, major histocompatibility complex I, or perforin were unable to clear WNV infection from CNS, had increased viral burden in the CNS, and displayed higher mortality rate after infection with WNV than wild-type mice [137,236].…”

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

“…Mice lacking IFN-γ or IFN-γ receptor exhibit increased viremia and viral burdens in lymphoid tissues leading to early CNS invasion and decreased survival [137]. Similarly, γδT cells, in part through action as IFN-γ producers, are necessary to limit WNV viremia [138].…”

Section: Mechanisms Of Peripheral Infection Pathogenesis and Host Dmentioning

confidence: 99%

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Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus-and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

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Section: Innate Immune Response To Arboviruses In the Cnsmentioning

confidence: 72%

Section: Viral Clearance From the Cnsmentioning

confidence: 99%

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Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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“…In addition, the mean time to death of caspase 3 Ϫ/Ϫ mice was significantly extended relative to wild-type mice (8.7 Ϯ 0.9 days versus 7.2 Ϯ 0.8 days, respectively; P ϭ 0.008). This phenotype of decreased death after IC WNV infection in a genetically deficient mouse is particularly striking and has not been observed with any other mouse strain (47,48,54).…”

Section: Caspase 3 Is Activated In the Cns After Wnv Infectionmentioning

confidence: 88%

Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis

Samuel¹,

Morrey

Diamond

2007

J Virol

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162

176

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West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that has become a significant global cause of viral encephalitis. To examine the mechanisms of WNV-induced neuronal death and the importance of apoptosis in pathogenesis, we evaluated the role of a key apoptotic regulator, caspase 3. WNV infection induced caspase 3 activation and apoptosis in the brains of wild-type mice. Notably, congenic caspase 3 ؊/؊ mice were more resistant to lethal WNV infection, although there were no significant differences in the tissue viral burdens or the kinetics of viral spread. Instead, decreased neuronal death was observed in the cerebral cortices, brain stems, and cerebella of caspase 3 ؊/؊ mice. Analogously, primary central nervous system (CNS)-derived neurons demonstrated caspase 3 activation and apoptosis after WNV infection, and treatment with caspase inhibitors or a genetic deficiency in caspase 3 significantly decreased virus-induced death. These studies establish that caspase 3-dependent apoptosis contributes to the pathogenesis of lethal WNV encephalitis and suggest possible novel therapeutic targets to restrict CNS injury.

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“…The levels of WNV specific IgM and IgG were detected by ELISA using purified WNV E protein as described previously [34]. The titer of neutralizing antibody was determined using a previously published plaque reduction neutralization assay protocol with BHK21 cells [34].…”

Section: Detection Of Wnv-specific Antibodiesmentioning

confidence: 99%

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

Shrestha

Chu

et al. 2008

Vaccine

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West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a severe central nervous system (CNS) infection in humans and animals. Although commercial vaccines are available for horses, none is currently approved for human use. In this study, we evaluated the efficacy and mechanism of immune protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV vaccine induced higher levels of specific and neutralizing antibodies compared to a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial and almost complete protection against a highly stringent lethal intracranial WNV challenge were observed in mice 60 days after single dose immunization with the DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with a single dose of DNA plasmid or inactivated vaccine, antigenspecific CD8 + T cells were induced and contributed to protective immunity as acquired or genetic deficiencies of CD8 + T cells lowered the survival rates. In contrast, in boosted animals, WNVspecific antibody titers were higher, survival rates after challenge were greater, and an absence of CD8 + T cells did not appreciably affect mortality. Overall, our experiments suggest that in mice, both inactivated WNV and DNA plasmid vaccines are protective after two doses, and the specific contribution of antibody and CD8 + T cells to vaccine immunity against WNV is modulated by the prime-boost strategy.

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Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection

Abstract: West Nile virus (WNV) causes a severe central nervous system (CNS) infection in humans

Cited by 178 publications

References 74 publications

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis

The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus

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