CD40 ligand exhibits a direct antiviral effect on Herpes Simplex Virus type-1 infection via a PI3K-dependent, autophagy-independent mechanism

Vlahava, Virginia-Maria; Eliopoulos, Aristides G.; Sourvinos, George

doi:10.1016/j.cellsig.2015.03.002

Cited by 5 publications

(4 citation statements)

References 62 publications

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“…Treating both normal and neoplastic cells with spautin-1 inhibits autophagy, as is indicated by decreased LC3II expression [ 41 , 43 , 45 – 47 , 63 – 73 ] and increased P62 expression [ 45 , 64 , 66 , 72 ] assessed by western blot. In our canine cell lines, we observed the opposite for LC3II; we saw either no change, or increased expression with increasing spautin-1 concentration ( Fig 3 ).…”

Section: Discussionmentioning

confidence: 99%

The autophagy inhibitor spautin-1, either alone or combined with doxorubicin, decreases cell survival and colony formation in canine appendicular osteosarcoma cells

et al. 2018

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Dogs diagnosed with appendicular osteosarcoma typically succumb to metastatic disease within a year of diagnosis. The current standard of care for curative intent, amputation followed by adjuvant chemotherapy, increases survival time but chemoresistance is a major contributor to mortality. Unfortunately, the mechanisms driving the progression of metastatic disease and the development of chemoresistance are unknown. One theory is that autophagy may contribute to chemoresistance by providing neoplastic cells with a mechanism to survive chemotherapy treatment. Our objective was to evaluate the effect of combining an autophagy inhibitor with a standard chemotherapeutic drug on response to chemotherapy in canine appendicular osteosarcoma cells. We hypothesized that combining the autophagy inhibitor spautin-1 with doxorubicin treatment would enhance chemoresponsiveness. Using commercial (D17) and primary cell lines derived from 1° and 2° sites of osteosarcoma, we showed that this combination treatment enhances cell killing and inhibits colony formation. Our findings support the theory that autophagy contributes to chemoresistance in canine appendicular osteosarcoma and indicate that adding an autophagy inhibitor to the standard of care has the potential to improve outcome.

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Section: Discussionmentioning

confidence: 99%

The autophagy inhibitor spautin-1, either alone or combined with doxorubicin, decreases cell survival and colony formation in canine appendicular osteosarcoma cells

et al. 2018

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“…CD40L is a type II tumor necrosis factor receptor (TNFR) superfamily transmembrane protein with a membrane-bound and a soluble form expressed principally by activated T cells and under severe inflammatory situations on natural killer cells and mast cells [15]. CD40L is a critical regulator of cellular and humoral immune responses in viral immunopathogenesis [16][17][18][19][20][21][22]. It also has identified roles in several autoimmune diseases [23][24][25][26][27][28], including neurodegenerative diseases such as MS [27,29] and Alzheimer's [30].…”

Section: Introductionmentioning

confidence: 99%

CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination

et al. 2021

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Neurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in the RSA59-induced neuroinflammation model of MS showed a protective role of CNS-infiltrating CD4+ T cells compared to their pathogenic role in the autoimmune model. The current study further investigated the molecular nexus between CD4+T cell-expressed CD40Ligand and microglia/macrophage-expressed CD40 using CD40L-/- mice. Results demonstrate CD40L expression in the CNS is modulated upon RSA59 infection. We show evidence that CD40L-/- mice are more susceptible to RSA59 induced disease due to reduced microglia/macrophage activation and significantly dampened effector CD4+ T recruitment to the CNS on day 10 p.i. Additionally, CD40L-/- mice exhibited severe demyelination mediated by phagocytic microglia/macrophages, axonal loss, and persistent poliomyelitis during chronic infection, indicating CD40-CD40L as host-protective against RSA59-induced demyelination. This suggests a novel target in designing prophylaxis for virus-induced demyelination and axonal degeneration, in contrast to immunosuppression which holds only for autoimmune mechanisms of inflammatory demyelination.

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“…It has been reported that CD40 L exhibits antiviral properties against HSV‐1 replication in vivo 126 . Further studies indicate that the activation of CD40 by the cognitive ligand CD40 L delays of the nucleus translocation of VP16, a possible mechanism to inhibit HSV‐1 replication 127 . Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is a ligand‐activated nuclear receptor that regulates the transcription of various genes.…”

Section: Hsv‐1 Vp16 Interacts With the Mineralocorticoid Receptor Nr3...mentioning

confidence: 99%

“… 126 Further studies indicate that the activation of CD40 by the cognitive ligand CD40 L delays of the nucleus translocation of VP16, a possible mechanism to inhibit HSV‐1 replication. 127 Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) is a ligand‐activated nuclear receptor that regulates the transcription of various genes. PPAR‐γ plays an essential role in adipogenesis and glucose homoeostasis.…”

Section: Hsv‐1 Vp16 Interacts With the Mineralocorticoid Receptor Nr3...mentioning

confidence: 99%

Host factors associated with either VP16 or VP16‐induced complex differentially affect HSV‐1 lytic infection

Ding

Neumann

Zhu

2022

Reviews in Medical Virology

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Herpes simplex virus type 1 (HSV‐1) is an important human pathogen with neurotropism. Following lytic infection in mucosal or skin epithelium, life‐long latency is established mainly in sensory neurons, which can periodically reactivate by stress, leading to recurrent disease and virus transmission. During the virus's productive infection, the tegument protein VP16, a component of HSV‐1 virion, is physically associated with two cellular factors, host cell factor‐1 (HCF‐1), and POU domain protein Oct‐1, to construct the VP16‐induced complex, which is essential to stimulate immediate early (IE)‐gene transcription as well as initiate the lytic programme. Apart from HCF‐1 and Oct‐1, VP16 also associates with a series of other host factors, making a VP16‐induced regulatory switch to either activate or inactivate virus gene transcription. In addition, VP16 has effects on distinct signalling pathways via binding to various host molecules that are essentially related to innate immune responses, RNA polymerases, molecular chaperones, and virus infection‐induced host shutoff. VP16 also functionally compensates for given host factors, such as PPAR‐γ and ß‐catenin. In this review, we provide an overview of the updated insights on the interplay between VP16 and the host factors that coordinate virus infection.

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CD40 ligand exhibits a direct antiviral effect on Herpes Simplex Virus type-1 infection via a PI3K-dependent, autophagy-independent mechanism

Cited by 5 publications

References 62 publications

The autophagy inhibitor spautin-1, either alone or combined with doxorubicin, decreases cell survival and colony formation in canine appendicular osteosarcoma cells

The autophagy inhibitor spautin-1, either alone or combined with doxorubicin, decreases cell survival and colony formation in canine appendicular osteosarcoma cells

CD40L protects against mouse hepatitis virus-induced neuroinflammatory demyelination

Host factors associated with either VP16 or VP16‐induced complex differentially affect HSV‐1 lytic infection

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