Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Detje, Claudia N.; Lienenklaus, Stefan; Chhatbar, Chintan; Spanier, Julia; Prajeeth, Chittappen Kandiyil; Soldner, Claudia; Tovey, Michaël G.; Schlüter, Dirk; Stangel, Martin; Kalinke, Ulrich

doi:10.1128/jvi.02044-14

Cited by 67 publications

(77 citation statements)

References 34 publications

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“…Inflammation in the central nervous system is characterized by marked activation of these glial cells [45]. Upon activation, glial cells are endowed with the ability to produce type I interferons, inflammatory cytokines, and chemokines [39, 46]. Multiple miRNAs can regulate human innate immune signaling pathways and mediate inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)

Wan

Ashraf

et al. 2016

Oncotarget

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MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulating the host immune response. Here we found that miR-22 is induced in glial cells upon stimulation with poly(I:C). Overexpression of miR-22 in the cultured cells resulted in decreased activity of interferon regulatory factor-3 and nuclear factor-kappa B, which in turn led to reduced expression of interferon-β and inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and chemokine (C-C motif) ligand 5, upon stimulation with poly(I:C), whereas knockdown of miR-22 had the opposite effect. We used a combination of bioinformatics and experimental techniques to demonstrate that mitochondrial antiviral signaling protein (MAVS), which positively regulates type I interferon production, is a novel target of miR-22. Overexpression of miR-22 decreased the activity of a luciferase reporter containing the MAVS 3′-untranslated region and led to decreased MAVS mRNA and protein levels. In contrast, ectopic expression of miR-22 inhibitor led to elevated MAVS expression. Collectively, our results demonstrate that miR-22 negatively regulates poly(I:C)-induced production of type I interferon and inflammatory cytokines via targeting MAVS.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)

Wan

Ashraf

et al. 2016

Oncotarget

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“…Previous work in our laboratories indicated that astrocytes are the main producers of IFN after infection of the CNS with La Crosse virus (8) or VSV (22), but how astrocytes might sense those viruses which preferentially replicate in neurons remained unclear. In the current study, we extended this observation by demonstrating that TMEV and RABV, two other virus species that also selectively replicate in neurons, showed the same behavior and preferentially triggered IFN-␤ synthesis in astrocytes of infected mouse brains.…”

Section: Discussionmentioning

confidence: 99%

Abortively Infected Astrocytes Appear To Represent the Main Source of Interferon Beta in the Virus-Infected Brain

Pfefferkorn

Kallfass

Lienenklaus

et al. 2016

J Virol

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“…Several recent studies used this approach to probe the brain's innate immune response to virus (49,51). Intranasal application of virus is technically simpler than intracerebral stereotactic injection and has the advantage that it interrogates a route of infection that may be a natural one.…”

Section: Discussionmentioning

confidence: 99%

The brain parenchyma has a type I interferon response that can limit virus spread

Drokhlyansky

Ayturk

Soh

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.

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Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Cited by 67 publications

References 34 publications

MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)

MicroRNA-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein (MAVS)

Abortively Infected Astrocytes Appear To Represent the Main Source of Interferon Beta in the Virus-Infected Brain

The brain parenchyma has a type I interferon response that can limit virus spread

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