Interferon-β suppresses herpes simplex virus type 1 replication in trigeminal ganglion cells through an RNase L-dependent pathway

Carr, Daniel J.J.; Al-Khatib, Khaldun; James, Cassandra M.; Silverman, Robert H.

doi:10.1016/s0165-5728(03)00216-9

Cited by 41 publications

(33 citation statements)

References 44 publications

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“…The NS3/4A protein complex of hepatitis C virus also blocks phosphorylation of IRF3 (34). Among the ISG, the antiviral activity of 2Ј5ЈOAS has been wellcharacterized (35,36), however, the complete spectrum of ISG with potential antiviral activity remains to be defined. In this context, it is of interest to note that the microarray analysis of our pIC-activated astrocytes identified viperin/cig5 as one of the most highly expressed genes.…”

Section: Discussionmentioning

confidence: 99%

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

Rivieccio¹,

Suh²,

Zhao³

et al. 2006

The Journal of Immunology

129

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TLR3 functions as a viral nucleic acid sentinel activated by dsRNA viruses and virus replication intermediates within intracellular vesicles. To explore the spectrum of genes induced in human astrocytes by TLR3, we used a microarray approach and the analog polyriboinosinic polyribocytidylic acid (pIC) as ligand. As expected for TLR activation, pIC induced a wide array of cytokines and chemokines known for their role in inflammatory responses, as well as up-regulation of the receptor itself. The data also showed activation of a broad spectrum of antiviral response genes. To determine whether pIC induced an antiviral state in astrocytes, a pseudotyped HIV viral particle, vesicular stomatitis virus g-env-HIV-1, was used. pIC significantly abrogated HIV-1 replication, whereas IL-1, which also potently activates astrocytes, did not. One of the most highly up-regulated genes on microarray was the protein viperin/cig5. We found that viperin/cig5 expression was dependent on IFN regulatory factor 3 and NF-κB signaling, and that repetitive stimulation with pIC, but not IL-1, further increased expression. Viperin induction could also be substantially inhibited by neutralizing Abs to IFN-β, as could HIV-1 replication. To explore a role for viperin in IFN-β-mediated inhibition of HIV-1, we used an RNA interference (RNAi) approach. RNAi directed against viperin, but not a scrambled RNAi, significantly inhibited viperin expression, and also significantly reversed pIC-induced inhibition of HIV-1 replication. We conclude that viperin contributes to the antiviral state induced by TLR3 ligation in astrocytes, supporting a role for astrocytes as part of the innate immune response against infection in the CNS.

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Section: Discussionmentioning

confidence: 99%

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

Rivieccio¹,

Suh²,

Zhao³

et al. 2006

The Journal of Immunology

129

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“…These proteins do, however, partially mediate antiviral resistance in mice for some viruses. Mice lacking PKR showed increased lethality following VSV infection (16,71) and more severe ocular HSV disease (7). Mice deficient in PKR and/or RNase L showed increased mortality following coxsackievirus infection (20).…”

Section: B-cell-and Cd8mentioning

confidence: 99%

PKR and RNase L Contribute to Protection against Lethal West Nile Virus Infection by Controlling Early Viral Spread in the Periphery and Replication in Neurons

Samuel

Whitby

Keller

et al. 2006

J Virol

226

249

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West Nile virus (WNV) is a neurotropic, mosquito-borne flavivirus that can cause lethal meningoencephalitis. Type I interferon (IFN) plays a critical role in controlling WNV replication, spread, and tropism. In this study, we begin to examine the effector mechanisms by which type I IFN inhibits WNV infection. Mice lacking both the interferon-induced, double-stranded-RNA-activated protein kinase (PKR) and the endoribonuclease of the 2,5-oligoadenylate synthetase-RNase L system (PKR ؊/؊ ؋ RL ؊/؊ ) were highly susceptible to subcutaneous WNV infection, with a 90% mortality rate compared to the 30% mortality rate observed in congenic wild-type mice. PKR ؊/؊ ؋ RL ؊/؊ mice had increased viral loads in their draining lymph nodes, sera, and spleens, which led to early viral entry into the central nervous system (CNS) and higher viral burden in neuronal tissues. Although mice lacking RNase L showed a higher CNS viral burden and an increased mortality, they were less susceptible than the PKR ؊/؊ ؋ RL ؊/؊ mice; thus, we also infer an antiviral role for PKR in the control of WNV infection. Notably, a deficiency in both PKR and RNase L resulted in a decreased ability of type I IFN to inhibit WNV in primary macrophages and cortical neurons. In contrast, the peripheral neurons of the superior cervical ganglia of PKR ؊/؊ ؋ RL ؊/؊ mice showed no deficiency in the IFN-mediated inhibition of WNV. Our data suggest that PKR and RNase L contribute to IFN-mediated protection in a cell-restricted manner and control WNV infection in peripheral tissues and some neuronal subtypes.

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“…RNase L degrades viral and cellular RNAs resulting in inhibition of protein synthesis (56). The 2Ј,5Ј-OAS/RNase L pathway has been shown to inhibit the replication of viruses belonging to different families, such as Picornaviridae (57,58), Hepadnaviridae (59), Paramyxoviridae (60), Herpesviridae (61), and Retroviridae (HIV-1) (62)(63)(64). MxA belongs to the GTPase superfamily of dynamin-like GTPases (65,66).…”

Section: E Pithelial Cells Of the Female Reproductive Tract (Frt)mentioning

confidence: 99%

Innate Immunity in the Human Female Reproductive Tract: Antiviral Response of Uterine Epithelial Cells to the TLR3 Agonist Poly(I:C)

Schaefer

Fahey

Wright

et al. 2005

The Journal of Immunology

237

243

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The objective of this study was to examine the expression of TLR by human primary uterine epithelial cells (UEC) and to determine whether exposure to the TLR agonist poly(I:C) would induce an antiviral response. The secretion of several cytokines and chemokines was examined as well as the mRNA expression of human β-defensin-1 and -2 (HBD1 and HBD2), IFN-β, and the IFN-β-stimulated genes myxovirus resistance gene 1 and 2′,5′ oligoadenylate synthetase. The expression of TLR1–9 by UEC was demonstrated by RT-PCR, with only TLR10 not expressed. Stimulation of UEC with the TLR3 agonist poly(I:C) induced the expression of the proinflammatory cytokines TNF-α, IL-6, GM-CSF, and G-CSF, as well as the chemokines CXCL8/IL-8, CCL2/MCP-1, and CCL4/MIP-1β. In addition, poly(I:C) exposure induced the mRNA expression of HBD1 and HBD2 by 6- and 4-fold, respectively. Furthermore, upon exposure to poly(I:C) UEC initiated a potent antiviral response resulting in the induction of IFN-β mRNA expression 70-fold and myxovirus resistance gene 1 and 2′,5′ oligoadenylate synthetase mRNA expression (107- and 96-fold), respectively. These results suggest that epithelial cells that line the uterine cavity are sensitive to viral infection and/or exposure to viral dsRNA released from killed epithelial cells. Not only do UEC release proinflammatory cytokines and chemokines that mediate the initiation of an inflammatory response and recruitment of immune cells to the site of infection, but they also express β-defensins, IFN-β, and IFN-β-stimulated genes that can have a direct inhibiting effect on viral replication.

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Interferon-β suppresses herpes simplex virus type 1 replication in trigeminal ganglion cells through an RNase L-dependent pathway

Cited by 41 publications

References 44 publications

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5

PKR and RNase L Contribute to Protection against Lethal West Nile Virus Infection by Controlling Early Viral Spread in the Periphery and Replication in Neurons

Innate Immunity in the Human Female Reproductive Tract: Antiviral Response of Uterine Epithelial Cells to the TLR3 Agonist Poly(I:C)

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