Zika virus infection modulates the metabolomic profile of microglial cells

Diop, Fodé; Vial, Thomas; Ferraris, Pauline; Wichit, Sineewanlaya; Bengue, Michèle; Hamel, Rodolphe; Talignani, Loïc; Liégeois, Florian; Pompon, Julien; Yssel, Hans; Marti, Guillaume; Missé, Dorothée

doi:10.1371/journal.pone.0206093

Cited by 62 publications

(53 citation statements)

References 50 publications

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“…Analysis of differential expressed circRNAs has revealed changes in the metabolism of fatty acids upon BmCPV infection ( Hu et al, 2018 ).All these reports have demonstrated that lipid-related metabolisms play vital roles in the life cycles of RNA viruses. It is worth noting that the virus-induced changes of cellular metabolic activity generally facilitate the progress of virus infection ( Diop et al, 2018 ; Tian et al, 2019 ). To date, the lipid metabolism in cells infected by double-stranded RNA (dsRNA) viruses, such as, BmCPV remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

Zhang

Shi

et al. 2021

Developmental & Comparative Immunology

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Bombyx mori cytoplasmic polyhedrosis virus (BmCPV)that belongs to the genus Cypovirus in the family of Reoviridae is one of the problematic pathogens in sericulture. In our previous study, we have found that lipid-related constituents in the host cellular membrane are associated with the BmCPV life cycle. It is important to note that the lipids not only affect the cellular biological processes, they also impact the virus life cycle. However, the intracellular lipid homeostasis in BmN cells after BmCPV infection remains unclear. Here, the lipid metabolism in BmCPV-infected BmN cells was studied by lipidomics analysis. Our results revealed that the intracellular lipid homeostasis was disturbed in BmN cells upon BmCPV infection. Major lipids constituents in cellular membrane were found to be significantly induced upon BmCPV infection, which included triglycerides, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phospholipids, glucoside ceramide, monoetherphosphatidylcholin, ceramide, ceramide phosphoethanolamine and cardiolipin. Further analysis of the pathways related to these altered lipids (such as PE and PC) showed that glycerophospholipid metabolism was one of the most enriched pathways. These results suggested that BmCPV may manipulate the lipid metabolism of cells for their own interest. The findings may facilitate a better understanding of the roles of lipid metabolic changes during virus infection in future studies.

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Section: Introductionmentioning

confidence: 99%

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

Zhang

Shi

et al. 2021

Developmental & Comparative Immunology

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“…However, hyperactivation of microglia induces chronic inflammation and neurodegeneration [ 30 ]. ZIKV-infected microglia exhibit an activated phenotype, characterized by the upregulation of several inflammatory cytokines and may also transmit the virus to other target cells in the brain [ 9 , 31 ]. To determine the role of IL-22 in the microglial profile during ZIKV infection, we analyzed the microglial phenotype in both WT and IL-22 -/- neonatal mice.…”

Section: Resultsmentioning

confidence: 99%

“…The mRNA levels of IFN-γ , as well as its inducible chemokines, CXCL9 and CXCL10 , were not changed significantly. However, the level of brain TNF-α , which is the main cytokine produced by microglia [ 31 , 32 ], was significantly decreased in IL-22 -/- mice (Fig. S3 ).…”

Section: Resultsmentioning

confidence: 99%

IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice

Liang

et al. 2020

J Neuroinflammation

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Background The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown. Methods The cellular source of IL-22 was identified in IFNAR -/- mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22 -/- mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8 + T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads. Results We found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16–19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22 -/- mice mounted more vigorous ZIKV-specific CD8 + T cell responses, which led to a more effective control of ZIKV in the brain. Conclusions Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

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“…The mRNA levels of IFN-γ, as well as its inducible chemokines, CXCL9 and CXCL10, were not changed signi cantly. However, the level of brain TNF-α, which is the main cytokine produced by microglia [27,28], was signi cantly decreased in IL-22 −/− mice (Fig. S3).…”

Section: Il-22 De Ciency Reduced Microglia Activation In Zikvinfectedmentioning

confidence: 98%

“…However hyperactivation of microglia induces chronic in ammation and neurodegeneration [26]. ZIKV-infected microglia exhibit an activated phenotype, characterized by upregulation of several in ammatory cytokines and may also transmit virus to other target cells in the brain [9,27]. To determine the role of IL-22 in microglial pro le during ZIKV infection, we analyzed the microglial phenotype in both IL-22 −/− and WT neonatal mice.…”

Section: Il-22 De Ciency Reduced Microglia Activation In Zikvinfectedmentioning

confidence: 99%

IL-22 hinders antiviral T cell responses and exacerbates neurological disorders in ZIKV-infected immunocompetent neonatal mice

Liang

et al. 2020

Preprint

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Background The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of neurological disorders and congenital defects. However, host immunity and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays a role in ZIKV infection is unknown. Methods The cellular source of IL-22 was identified in IFNAR−/− mice and WT neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old wild-type (WT) and IL-22−/− mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, we infected mouse primary astrocytes in vitro, and characterized the reactive astrocyte phenotype. Human glial cell line was also infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression and viral loads. Results We found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to develop weight loss, staggered steps, bilateral hind limb paralysis, weakness at 10 days post-infection (dpi), and ultimately succumbed to infection at 16–19 dpi. Surprisingly, IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly reduced the incidence of neurological disorders and mortality. ZIKV infection facilitated a neurotoxic polarization of A1-prone astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a marginal effect on glial cells in vitro, IL-22−/− mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain. Conclusions Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

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Zika virus infection modulates the metabolomic profile of microglial cells

Cited by 62 publications

References 50 publications

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

Characterization of the lipidomic profile of BmN cells in response to Bombyx mori cytoplasmic polyhedrosis virus infection

IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice

IL-22 hinders antiviral T cell responses and exacerbates neurological disorders in ZIKV-infected immunocompetent neonatal mice

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