Interferon-Induced Tetherin Restricts Vesicular Stomatitis Virus Release in Neurons

Sarojini, Sreeja; Theofanis, Thana; Reiss, Carol Shoshkes

doi:10.1089/dna.2011.1384

Cited by 31 publications

(19 citation statements)

References 82 publications

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“…Tetherin expression was also evaluated in the TG by PCR at day 5 pi (Supplemental Figure 1b) in light of evidence showing tetherin expression in neurons 30,31 and the enhanced trafficking of HSV-1 from the cornea to the TG in STING −/− and CD118 −/− mice observed herein (Supplemental Figure 1a). Though STING is required for tetherin expression in the corneal epithelium (Figure 4c, Supplemental Movie 1), tetherin is upregulated in the TG of STING −/− mice similarly to WT at an approximate 8-fold increase over UI yet conspicuously absent in CD118 −/− TG at day 5 pi (Supplemental Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin

Royer

Carr

2016

Mucosal Immunology

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Type 1 interferons (IFNα/β) mediate immunologic host resistance to numerous viral infections including herpes simplex virus type 1 (HSV-1). The pathways responsible for IFNα/β signaling during the innate immune response to acute HSV-1 infection in the cornea are incompletely understood. Using a murine ocular infection model, we hypothesized that the stimulator of IFN genes (STING) mediates resistance to HSV-1 infection at the ocular surface and preserves the structural integrity of this mucosal site. Viral pathogenesis, tissue pathology, and host immune responses during ocular HSV-1 infection were characterized by plaque assay, esthesiometry, pachymetry, immunohistochemistry, flow cytometry, and siRNA transfection in wildtype C57BL/6 (WT), STING-deficient (STING−/−), and IFNα/β receptor-deficient (CD118−/−) mice at days 3–5 post infection. The presence of STING was critical for sustained control of HSV-1 replication in the corneal epithelium and neuroinvasion, but loss of STING had a negligible impact with respect to gross tissue pathology. Auxiliary STING-independent IFNα/β signaling pathways were responsible for maintenance of the corneal integrity. Lymphatic vessels, mast cells, and sensory innervation were compromised in CD118−/− mice concurrent with increased tissue edema. STING-dependent signaling led to the upregulation of tetherin, a viral restriction factor we identify is important in containing the spread of HSV-1 in vivo.

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Section: Resultsmentioning

confidence: 99%

A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin

Royer

Carr

2016

Mucosal Immunology

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“…were similar in spleens and salivary glands on days 3 and 14 p.i., respectively (Figure 2B). It has been reported that BST2 inhibits the release of VSV from infected cells (19, 20) so we next infected mice i.v. with VSV-OVA.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Paradoxical Roles of BST2/Tetherin in Promoting Type I IFN Response and Viral Infection

Swiecki

Wang

Gilfillan

et al. 2012

The Journal of Immunology

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Bone marrow stromal antigen-2 (BST2) is a transmembrane protein that prevents virus release from infected cells. It was also reported that BST2 inhibits type-I-interferon (IFN-I) production by plasmacytoid DC (pDC). To determine BST2 impact on antiviral responses in vivo we generated BST2−/− mice. Following infection with a murine retrovirus, BST2−/− mice had slightly elevated viral loads; however, infection with other enveloped viruses revealed unexpected roles of BST2. BST2−/− mice showed reduced IFN-I production by pDC. Moreover, BST2−/− mice had lower viral titers in lungs following intranasal infection with VSV-OVA and influenza B, and increased numbers of virus-specific CD8+T cells in the lungs, suggesting that BST2 may facilitate entry and/or replication of enveloped viruses and modulate priming of CD8+T cells. These findings suggest complex roles of BST2 beyond retroviral control in vivo, possibly reflecting the involvement of BST2 in endocytosis and intracellular trafficking of viruses, viral nucleic acids and antigens.

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“…BST2 is an ISG encoded type 2 transmembrane protein that functions as an antiviral restriction factor. Importantly, recent studies have indicated that BST2 inhibits VSV release by neuroblastoma cells (Sarojini et al, 2011). In addition, the IFN-induced with tetratricopeptide repeats 2 (Ifit2) gene has been implicated in VSV neurotropism as Ifit2 deficient animals show increased susceptibility to VSV infection delivered via the i.n.…”

Section: Neurotropism Of Vsvmentioning

confidence: 99%

Understanding and altering cell tropism of vesicular stomatitis virus

Hastie¹,

Cataldi²,

Marriott³

et al. 2013

Virus Research

115

116

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Vesicular stomatitis virus (VSV) is a prototypic nonsegmented negative-strand RNA virus. VSV’s broad cell tropism makes it a popular model virus for many basic research applications. In addition, a lack of preexisting human immunity against VSV, inherent oncotropism and other features make VSV a widely used platform for vaccine and oncolytic vectors. However, VSV’s neurotropism that can result in viral encephalitis in experimental animals needs to be addressed for the use of the virus as a safe vector. Therefore, it is very important to understand the determinants of VSV tropism and develop strategies to alter it. VSV glycoprotein (G) and matrix (M) protein play major roles in its cell tropism. VSV G protein is responsible for VSV broad cell tropism and is often used for pseudotyping other viruses. VSV M affects cell tropism via evasion of antiviral responses, and M mutants can be used to limit cell tropism to cell types defective in interferon signaling. In addition, other VSV proteins and host proteins may function as determinants of VSV cell tropism. Various approaches have been successfully used to alter VSV tropism to benefit basic research and clinically relevant applications.

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Interferon-Induced Tetherin Restricts Vesicular Stomatitis Virus Release in Neurons

Cited by 31 publications

References 82 publications

A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin

A STING-dependent innate-sensing pathway mediates resistance to corneal HSV-1 infection via upregulation of the antiviral effector tetherin

Cutting Edge: Paradoxical Roles of BST2/Tetherin in Promoting Type I IFN Response and Viral Infection

Understanding and altering cell tropism of vesicular stomatitis virus

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