Interferon Gamma Prolongs Survival of Varicella-Zoster Virus-Infected Human Neurons<i>In Vitro</i>

Baird, Nicholas L.; Bowlin, Jacqueline L.; Hotz, Taylor; Cohrs, Randall J.; Gilden, Don

doi:10.1128/jvi.00594-15

Cited by 19 publications

(18 citation statements)

References 17 publications

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“…IFN-␥, the sole member of the type II interferon family (17), produced during viral infection stimulates transcription of cellular genes that mediate antiviral responses against several herpesviruses (18)(19)(20). IFN-␥ is produced following primary VZV infection (21,22) and inhibits VZV production in human neurons (17) and human embryonic lung fibroblasts (23). VZV reactivation correlates with a decline in IFN-␥-producing immune cells (24).…”

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confidence: 99%

Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner

Shakya

O’Callaghan

Kim

2019

J Virol

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The major immediate early 62 (IE62) protein of varicella-zoster virus (VZV) is delivered to newly infected cell nuclei, where it initiates VZV replication by transactivating viral immediate early (IE), early (E), and late (L) genes. Interferon gamma (IFN-γ) is a potent cytokine produced following primary VZV infection. Furthermore, VZV reactivation correlates with a decline in IFN-γ-producing immune cells. Our results showed that treatment with 20 ng/ml of IFN-γ completely reduced intracellular VZV yield in A549 lung epithelial cells, MRC-5 lung fibroblasts, and ARPE-19 retinal epithelial cells at 4 days post-VZV infection. However, IFN-γ reduced virus yield only 2-fold in MeWo melanoma cells compared to that of untreated cells. IFN-β significantly inhibited VZV replication in both ARPE-19 and MeWo cells. In luciferase assays with VZV open reading frame 61 (ORF61) promoter reporter plasmid, IFN-γ abrogated the transactivation activity of IE62 by 95%, 97%, and 89% in A549, ARPE-19, and MRC-5 cells, respectively. However, IFN-γ abrogated IE62’s transactivation activity by 16% in MeWo cells, indicating that IFN-γ inhibits VZV replication as well as IE62-mediated transactivation in a cell line-dependent manner. The expression of VZV IE62 and ORF63 suppressed by IFN-γ was restored by JAK1 inhibitor treatment, indicating that the inhibition of VZV replication is mediated by JAK/STAT1 signaling. In the presence of IFN-γ, knockdown of interferon response factor 1 (IRF1) increased VZV replication. Ectopic expression of IRF1 reduced VZV yields 4,000-fold in MRC-5 and ARPE-19 cells but 3-fold in MeWo cells. These results suggest that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. IMPORTANCE Our results showed that IFN-γ significantly inhibited VZV replication in a cell line-dependent manner. IFN-γ inhibited VZV gene expression after the immediate early stage of infection and abrogated IE62-mediated transactivation. These results suggest that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. Understanding the mechanisms by which IFN-γ plays a role in VZV gene programming may be important in determining the tissue restriction of VZV.

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confidence: 99%

Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner

Shakya

O’Callaghan

Kim

2019

J Virol

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“…IFNγ could profoundly inhibit VZV production in ARPE-19, A549, MRC-5 but had only very limited capacity to inhibit infection in MeWo cells, where IFNβ retained the capacity to significantly reduce viral yield (120). IFNγ could also promote survival of VZV infected neurons to potentially ensure the efficient establishment of latency (121). More recently, Como and colleagues demonstrated that Type I IFNs had an inhibitory effect on VZV replication and spread in VZV infected human iPSC derived neurons in vitro (122).…”

Section: Vzv Modulation Of Ifn In Immune Cellsmentioning

confidence: 99%

Manipulation of the Innate Immune Response by Varicella Zoster Virus

et al. 2020

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Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and shingles (herpes zoster). VZV and other members of the herpesvirus family are distinguished by their ability to establish a latent infection, with the potential to reactivate and spread virus to other susceptible individuals. This lifelong relationship continually subjects VZV to the host immune system and as such VZV has evolved a plethora of strategies to evade and manipulate the immune response. This review will focus on our current understanding of the innate anti-viral control mechanisms faced by VZV. We will also discuss the diverse array of strategies employed by VZV to regulate these innate immune responses and highlight new knowledge on the interactions between VZV and human innate immune cells.Keywords: varicella-zoster virus, immune evasion, innate immune response, herpes zoster (HZ), varicella (chickenpox) Pathogenesis of VZV Reactivation and LatencyReactivation from latency causes herpes zoster (shingles), a neurocutaneous disease which occurs in 10-20% of seropositive individuals and involves anterograde axonal transport of virus Frontiers in Immunology | www.frontiersin.org

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“…Over the last few years, the ield of VZV latency and reactivation has greatly advanced due to the derivation of human neurons to perform mechanistic studies in vitro, and the advanced molecular techniques which have led to the identi ication of VLT in vivo [196]. Studies have shown that types I and II IFNs inhibit viral replication and that IFN-γ inhibits transcription, replication, and production of neurons derived from iPSCs [196][197][198]. Hence, IFNs could be used to induce a VZV latent phenotype in human neurons or to inhibit VZV reactivation [196].…”

Section: Animal and Other Experimental Models For Vzvmentioning

confidence: 99%

The beneficial effects of varicella zoster virus

Al-Anazi¹,

Wk²,

Al-Jasser³

2019

J Hematol Clin Res

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Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the benefi cial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported benefi cial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

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Interferon Gamma Prolongs Survival of Varicella-Zoster Virus-Infected Human NeuronsIn Vitro

Cited by 19 publications

References 17 publications

Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner

Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner

Manipulation of the Innate Immune Response by Varicella Zoster Virus

The beneficial effects of varicella zoster virus

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