Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells

Bulstrode, Harry; Girdler, Gemma; Gracia, Tannia; Aivazidis, Alexander; Moutsopoulos, Ilias; Young, Adam M. H.; Hancock, John F.; He, Xiaoling; Ridley, Katherine; Xu, Zhaoyang; Stockley, John H.; Finlay, John B.; Hallou, Clement; Fajardo, Teodoro; Fountain, Daniel M; Dongen, Stijn van; Joannides, Alexis; Morris, Robert; Mair, Richard; Watts, Colin; Santarius, Thomas; Price, Stephen J.; Hutchinson, Peter J.; Hodson, Emma J.; Pollard, Steven M.; Mohorianu, Irina; Barker, Roger A.; Sweeney, Trevor R.; Bayraktar, Ömer; Gergely, Fanni; Rowitch, David H.

doi:10.1016/j.neuron.2022.09.002

Cited by 12 publications

(6 citation statements)

References 74 publications

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“…More interestingly, we also demonstrate here that the treatment with type 1 interferon beta (IFNβ), which is a well-known immunomodulator capable of decreasing inflammation and of rescuing the CZS phenotype ultimately characterized by the microcephaly (Bulstrode et al, 2022) restores the Ndel1 activity to the levels of the uninfected healthy control mice (Figure 8). Interestingly, productive ZIKV infection in human developing brain and glioblastoma (GBM, which is an adult brain cancer) primary tissue explants, both contain SOX2+ neural progenitors, proved that human developing brain is uniformly vulnerable to ZIKV infection while GBM was more refractory, which correlated with an innate immune expression signature (Bulstrode et al, 2022). Moreover, GBM-derived CD11b + microglia/ macrophages were necessary and sufficient to protect neuronal progenitors against ZIKV infection in a non-cell autonomous manner, as CD11b+ conditioned medium and IFNβ treatment rendered human developing brain progenitor lines and explants refractory to ZIKV (Bulstrode et al, 2022).…”

Section: Discussionmentioning

confidence: 69%

“…Interestingly, productive ZIKV infection in human developing brain and glioblastoma (GBM, which is an adult brain cancer) primary tissue explants, both contain SOX2+ neural progenitors, proved that human developing brain is uniformly vulnerable to ZIKV infection while GBM was more refractory, which correlated with an innate immune expression signature (Bulstrode et al, 2022). Moreover, GBM-derived CD11b + microglia/ macrophages were necessary and sufficient to protect neuronal progenitors against ZIKV infection in a non-cell autonomous manner, as CD11b+ conditioned medium and IFNβ treatment rendered human developing brain progenitor lines and explants refractory to ZIKV (Bulstrode et al, 2022). Also, IFNβ treatment demonstrated a neuroprotective effect in brain organoids infected by ZIKV by rescuing organoids growth and size and also reverting the transcriptional changes caused by ZIKV infection (Krenn et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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Assessing the role of Ndel1 oligopeptidase activity in congenital Zika syndrome: Potential predictor of congenital syndrome endophenotype and treatment response

Christoff,

Nani,

Lessa

et al. 2023

Journal of Neurochemistry

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Maternal infections are among the main risk factors for cognitive impairments in the offspring. Zika virus (ZIKV) can be transmitted vertically, causing a set of heterogeneous birth defects, such as microcephaly, ventriculomegaly and corpus callosum dysgenesis. Nuclear distribution element like‐1 (Ndel1) oligopeptidase controls crucial aspects of cerebral cortex development underlying cortical malformations. Here, we examine Ndel1 activity in an animal model for ZIKV infection, which was associated with deregulated corticogenesis. We observed here a reduction in Ndel1 activity in the forebrain associated with the congenital syndrome induced by ZIKV isolates, in an in utero and postnatal injections of different inoculum doses in mice models. In addition, we observed a strong correlation between Ndel1 activity and brain size of animals infected by ZIKV, suggesting the potential of this measure as a biomarker for microcephaly. More importantly, the increase of interferon (IFN)‐beta signaling, which was used to rescue the ZIKV infection outcomes, also recovered Ndel1 activity to levels similar to those of uninfected healthy control mice, but with no influence on Ndel1 activity in uninfected healthy control animals. Taken together, we demonstrate for the first time here an association of corticogenesis impairments determined by ZIKV infection and the modulation of Ndel1 activity. Although further studies are still necessary to clarify the possible role(s) of Ndel1 activity in the molecular mechanism(s) underlying the congenital syndrome induced by ZIKV, we suggest here the potential of monitoring the Ndel1 activity to predict this pathological condition at early stages of embryos or offspring development, during while the currently employed methods are unable to detect impaired corticogenesis leading to microcephaly. Ndel1 activity may also be possibly used to follow up the positive response to the treatment, such as that employing the IFN‐beta that is able to rescue the ZIKV‐induced brain injury.image

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Assessing the role of Ndel1 oligopeptidase activity in congenital Zika syndrome: Potential predictor of congenital syndrome endophenotype and treatment response

Christoff,

Nani,

Lessa

et al. 2023

Journal of Neurochemistry

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“…Contrarily, glioma slice cultures exhibit resistance to Zika virus infection unlike NPC, which is attributed to interferon-beta secretion by myeloid cells in the glioblastoma tumor microenvironment (132,133). The combination of CDK4/6 inhibitors with ZIKV-LAV enhances the selective replication of the vaccine, resulting in significant inhibition of tumor growth and prolonged survival in glioma mice.…”

Section: Zika Virusmentioning

confidence: 99%

Advances in oncolytic herpes simplex virus and adenovirus therapy for recurrent glioma

Hu,

Liao,

Tao

et al. 2023

Front. Immunol.

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Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing new therapeutic strategies. Oncolytic viruses have emerged as a promising option. Oncolytic viruses selectively replicate within tumor cells, destroying them and stimulating the immune system for an enhanced anticancer response. Among Oncolytic viruses investigated for recurrent gliomas, oncolytic herpes simplex virus and oncolytic adenovirus show notable potential. Genetic modifications play a crucial role in optimizing their therapeutic efficacy. Different generations of replicative conditioned oncolytic human adenovirus and oncolytic HSV have been developed, incorporating specific modifications to enhance tumor selectivity, replication efficiency, and immune activation. This review article summarizes these genetic modifications, offering insights into the underlying mechanisms of Oncolytic viruses’ therapy. It also aims to identify strategies for further enhancing the therapeutic benefits of Oncolytic viruses. However, it is important to acknowledge that additional research and clinical trials are necessary to establish the safety, efficacy, and optimal utilization of Oncolytic viruses in treating recurrent glioblastoma.

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“…Type I interferon responses have been shown to play a major role in protection from ZIKV infection, as demonstrated in mice that lack either IFNα or the receptors for IFNα [ 96 , 97 , 98 , 99 ]. Bulstrode et al demonstrated that IFNβ produced by myeloid cells significantly restricts ZIKV infection of progenitor cells in primary tissue explants [ 100 ]. Though Type I IFNs clearly suppress ZIKV infection, they have also been shown to play an ambivalent role.…”

Section: Zika Virus Infection and Immune Responsesmentioning

confidence: 99%

Zika Virus—A Reemerging Neurotropic Arbovirus Associated with Adverse Pregnancy Outcomes and Neuropathogenesis

Elliott,

Mattapallil

2024

Pathogens

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Zika virus (ZIKV) is a reemerging flavivirus that is primarily spread through bites from infected mosquitos. It was first discovered in 1947 in sentinel monkeys in Uganda and has since been the cause of several outbreaks, primarily in tropical and subtropical areas. Unlike earlier outbreaks, the 2015–2016 epidemic in Brazil was characterized by the emergence of neurovirulent strains of ZIKV strains that could be sexually and perinatally transmitted, leading to the Congenital Zika Syndrome (CZS) in newborns, and Guillain-Barre Syndrome (GBS) along with encephalitis and meningitis in adults. The immune response elicited by ZIKV infection is highly effective and characterized by the induction of both ZIKV-specific neutralizing antibodies and robust effector CD8+ T cell responses. However, the structural similarities between ZIKV and Dengue virus (DENV) lead to the induction of cross-reactive immune responses that could potentially enhance subsequent DENV infection, which imposes a constraint on the development of a highly efficacious ZIKV vaccine. The isolation and characterization of antibodies capable of cross-neutralizing both ZIKV and DENV along with cross-reactive CD8+ T cell responses suggest that vaccine immunogens can be designed to overcome these constraints. Here we review the structural characteristics of ZIKV along with the evidence of neuropathogenesis associated with ZIKV infection and the complex nature of the immune response that is elicited by ZIKV infection.

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Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells

Cited by 12 publications

References 74 publications

Assessing the role of Ndel1 oligopeptidase activity in congenital Zika syndrome: Potential predictor of congenital syndrome endophenotype and treatment response

Assessing the role of Ndel1 oligopeptidase activity in congenital Zika syndrome: Potential predictor of congenital syndrome endophenotype and treatment response

Advances in oncolytic herpes simplex virus and adenovirus therapy for recurrent glioma

Zika Virus—A Reemerging Neurotropic Arbovirus Associated with Adverse Pregnancy Outcomes and Neuropathogenesis

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