Cellular and Molecular Life Sciences最新文献

{"title":"SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses.","authors":"Thien-Phong Vu Manh, Carla Gouin, Julien De Wolf, Luc Jouneau, Florentina Pascale, Claudia Bevilacqua, Meriadeg Ar Gouilh, Bruno Da Costa, Christophe Chevalier, Matthieu Glorion, Laurent Hannouche, Céline Urien, Jérôme Estephan, Antoine Magnan, Morgan Le Guen, Quentin Marquant, Delphyne Descamps, Marc Dalod, Isabelle Schwartz-Cornil, Edouard Sage","doi":"10.1007/s00018-024-05322-z","DOIUrl":"10.1007/s00018-024-05322-z","url":null,"abstract":"<p><p>Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"351"},"PeriodicalIF":6.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis.","authors":"Maarten Swart, Andia N Redpath, Joy Ogbechi, Ryan Cardenas, Louise Topping, Ewoud B Compeer, Michael Goddard, Anastasios Chanalaris, Richard Williams, Daniel S Brewer, Nicola Smart, Claudia Monaco, Linda Troeberg","doi":"10.1007/s00018-024-05333-w","DOIUrl":"10.1007/s00018-024-05333-w","url":null,"abstract":"<p><p>Heparan sulfate (HS) proteoglycans are important regulators of cellular responses to soluble mediators such as chemokines, cytokines and growth factors. We profiled changes in expression of genes encoding HS core proteins, biosynthesis enzymes and modifiers during macrophage polarisation, and found that the most highly regulated gene was Sulf2, an extracellular HS 6-O-sulfatase that was markedly downregulated in response to pro-inflammatory stimuli. We then generated Sulf2^+/- bone marrow chimeric mice and examined inflammatory responses in antigen-induced arthritis, as a model of rheumatoid arthritis. Resolution of inflammation was impaired in myeloid Sulf2^+/- chimeras, with elevated joint swelling and increased abundance of pro-arthritic Th17 cells in synovial tissue. Transcriptomic and in vitro analyses indicated that Sulf2 deficiency increased type I interferon signaling in bone marrow-derived macrophages, leading to elevated expression of the Th17-inducing cytokine IL6. This establishes that dynamic remodeling of HS by Sulf2 limits type I interferon signaling in macrophages, and so protects against Th17-driven pathology.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"350"},"PeriodicalIF":6.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution.","authors":"Paula M Wagner, Mauricio A Salgado, Ornella Turani, Santiago J Fornasier, Gabriela A Salvador, Andrea M Smania, Cecilia Bouzat, Mario E Guido","doi":"10.1007/s00018-024-05355-4","DOIUrl":"10.1007/s00018-024-05355-4","url":null,"abstract":"<p><p>The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O₂ levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"348"},"PeriodicalIF":6.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lys-63-specific deubiquitinase BRCC36 enhances the sensitivity of multiple myeloma cells to lenalidomide by inhibiting lysosomal degradation of cereblon.","authors":"Busong Wang, Min Li, Dan Cao, Qing Sun, Wenjun Yu, Jingjing Ma, Haigang Ren, Guoqiang Xu, Liang Zhou","doi":"10.1007/s00018-024-05390-1","DOIUrl":"10.1007/s00018-024-05390-1","url":null,"abstract":"<p><p>Multiple myeloma (MM) is the second most common hematological tumor in adults. Immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide (Len), are effective drugs for the treatment of multiple myeloma. Len can recruit IKZF1 and IKZF3 to cereblon (CRBN), a substrate receptor of the cullin 4-RING E3 ligase (CRL4), promote their ubiquitination and degradation, and finally inhibit the proliferation of myeloma cells. However, MM patients develop resistance to IMiDs over time, leading to disease recurrence and deterioration. To explore the possible approaches that may enhance the sensitivity of IMiDs to MM, in this study, we used the proximity labeling technique TurboID and quantitative proteomics to identify Lys-63-specific deubiquitinase BRCC36 as a CRBN-interacting protein. Biochemical experiments demonstrated that BRCC36 in the BRISC complex protects CRBN from lysosomal degradation by specifically cleaving the K63-linked polyubiquitin chain on CRBN. Further studies found that a small-molecule compound SHIN1, which binds to BRISC complex subunit SHMT2, can upregulate CRBN by elevating BRCC36. The combination of SHIN1 and Len can further increase the sensitivity of MM cells to IMiDs. Therefore, this study provides the basis for the exploration of a possible strategy for the SHIN1 and Len combination treatment for MM.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"349"},"PeriodicalIF":6.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel CDKL5 targets identified in human iPSC-derived neurons.","authors":"Sean Massey, Ching-Seng Ang, Nadia M Davidson, Anita Quigley, Ben Rollo, Alexander R Harris, Robert M I Kapsa, John Christodoulou, Nicole J Van Bergen","doi":"10.1007/s00018-024-05389-8","DOIUrl":"10.1007/s00018-024-05389-8","url":null,"abstract":"<p><p>CDKL5 Deficiency Disorder (CDD) is a debilitating epileptic encephalopathy disorder affecting young children with no effective treatments. CDD is caused by pathogenic variants in Cyclin-Dependent Kinase-Like 5 (CDKL5), a protein kinase that regulates key phosphorylation events in neurons. For therapeutic intervention, it is essential to understand molecular pathways and phosphorylation targets of CDKL5. Using an unbiased phosphoproteomic approach we identified novel targets of CDKL5, including GTF2I, PPP1R35, GATAD2A and ZNF219 in human iPSC-derived neuronal cells. The phosphoserine residue in the target proteins lies in the CDKL5 consensus motif. We validated direct phosphorylation of GTF2I and PPP1R35 by CDKL5 using complementary approaches. GTF2I controls axon guidance, cell cycle and neurodevelopment by regulating expression of neuronal genes. PPP1R35 is critical for centriole elongation and cilia morphology, processes that are impaired in CDD. PPP1R35 interacts with CEP131, a known CDKL5 phospho-target. GATAD2A and ZNF219 belong to the Nucleosome Remodelling Deacetylase (NuRD) complex, which regulates neuronal activity-dependent genes and synaptic connectivity. In-depth knowledge of molecular pathways regulated by CDKL5 will allow a better understanding of druggable disease pathways to fast-track therapeutic development.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"347"},"PeriodicalIF":6.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low intensity repetitive transcranial magnetic stimulation enhances remyelination by newborn and surviving oligodendrocytes in the cuprizone model of toxic demyelination.","authors":"Phuong Tram Nguyen, Kalina Makowiecki, Thomas S Lewis, Alastair J Fortune, Mackenzie Clutterbuck, Laura A Reale, Bruce V Taylor, Jennifer Rodger, Carlie L Cullen, Kaylene M Young","doi":"10.1007/s00018-024-05391-0","DOIUrl":"10.1007/s00018-024-05391-0","url":null,"abstract":"<p><p>In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"346"},"PeriodicalIF":6.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from BMSCs in osteogenic differentiation promote type H blood vessel angiogenesis through miR-150-5p mediated metabolic reprogramming of endothelial cells.","authors":"Feng Wu, Chengchao Song, Guanqi Zhen, Qin Jin, Wei Li, Xiongjie Liang, Wenbo Xu, Wenhui Guo, Yang Yang, Wei Dong, Anlong Jiang, Pengyu Kong, Jinglong Yan","doi":"10.1007/s00018-024-05371-4","DOIUrl":"10.1007/s00018-024-05371-4","url":null,"abstract":"<p><p>Osteogenesis is tightly coupled with angiogenesis spatiotemporally. Previous studies have demonstrated that type H blood vessel formed by endothelial cells with high expression of CD31 and Emcn (CD31^hi Emcn^hi ECs) play a crucial role in bone regeneration. The mechanism of the molecular communication around CD31^hi Emcn^hi ECs and bone mesenchymal stem cells (BMSCs) in the osteogenic microenvironment is unclear. This study indicates that exosomes from bone mesenchymal stem cells with 7 days osteogenic differentiation (7D-BMSCs-exo) may promote CD31^hi Emcn^hi ECs angiogenesis, which was verified by tube formation assay, qRT-PCR, Western blot, immunofluorescence staining and µCT assays etc. in vitro and in vivo. Furthermore, by exosomal miRNA microarray and WGCNA assays, we identified downregulated miR-150-5p as the most relative hub gene coupling osteogenic differentiation and type H blood vessel angiogenesis. With bioinformatics assays, dual luciferase reporter experiments, qRT-PCR and Western blot assays, SOX2(SRY-Box Transcription Factor 2) was confirmed as a novel downstream target gene of miR-150-5p in exosomes, which might be a pivotal mechanism regulating CD31^hi Emcn^hi ECs formation. Additionally, JC-1 immunofluorescence staining, Western blot and seahorse assay results showed that the overexpression of SOX2 could shift metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis to enhance the CD31^hi Emcn^hi ECs formation. The PI3k/Akt signaling pathway might play a key role in this process. In summary, BMSCs in osteogenic differentiation might secrete exosomes with low miR-150-5p expression to induce type H blood vessel formation by mediating SOX2 overexpression in ECs. These findings might reveal a molecular mechanism of osteogenesis coupled with type H blood vessel angiogenesis in the osteogenic microenvironment and provide a new therapeutic target or cell-free remedy for osteogenesis impaired diseases.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"344"},"PeriodicalIF":6.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A8/A9-activated IFNγ⁺ NK cells trigger β-cell necroptosis in hepatitis B virus-associated liver cirrhosis.","authors":"Xuehui Li, Liang Hong, MingHui Ru, Rui Cai, Yuting Meng, Baohua Wang, Hongyan Diao, Lanjuan Li, Zhongwen Wu","doi":"10.1007/s00018-024-05365-2","DOIUrl":"10.1007/s00018-024-05365-2","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear.</p><p><strong>Methods: </strong>Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet β cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation.</p><p><strong>Results: </strong>Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated β cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL₄) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased β cells necroptosis compared with those treated with CCL₄. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE.</p><p><strong>Conclusion: </strong>Together, the data indicate that IFN-γ produced by NK cells induces β cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"345"},"PeriodicalIF":6.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.","authors":"Mercedes Mirasierra, Antonio Fernández-Pérez, Blanca Lizarbe, Noelia Keiran, Laura Ruiz-Cañas, María José Casarejos, Sebastián Cerdán, Joan Vendrell, Sonia Fernández-Veledo, Mario Vallejo","doi":"10.1007/s00018-024-05384-z","DOIUrl":"10.1007/s00018-024-05384-z","url":null,"abstract":"<p><p>The coordination of food intake, energy storage, and expenditure involves complex interactions between hypothalamic neurons and peripheral tissues including pancreatic islets, adipocytes, muscle, and liver. Previous research shows that deficiency of the transcription factor Alx3 alters pancreatic islet-dependent glucose homeostasis. In this study we carried out a comprehensive assessment of metabolic alterations in Alx3 deficiency. We report that Alx3-deficient mice exhibit decreased food intake without changes in body weight, along with reduced energy expenditure and altered respiratory exchange ratio. Magnetic resonance imaging reveals increased adiposity and decreased muscle mass, which was associated with markers of motor and sympathetic denervation. By contrast, Alx3-deficient mice on a high-fat diet show attenuated weight gain and improved insulin sensitivity, compared to control mice. Gene expression analysis demonstrates altered lipogenic and lipolytic gene profiles. In wild type mice Alx3 is expressed in hypothalamic arcuate nucleus neurons, but not in major peripheral metabolic organs. Functional diffusion-weighted magnetic resonance imaging reveals selective hypothalamic responses to fasting in the arcuate nucleus of Alx3-deficient mice. Additionally, altered expression of proopiomelanocortin and melanocortin-3 receptor mRNA in the hypothalamus suggests impaired regulation of feeding behavior. This study highlights the crucial role for Alx3 in governing food intake, energy homeostasis, and metabolic nutrient partitioning, thereby influencing body mass composition.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"343"},"PeriodicalIF":6.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.","authors":"Shuang Li, Yuanyang Xie, Changyin Yu, Chunfu Zheng, Zucai Xu","doi":"10.1007/s00018-024-05369-y","DOIUrl":"10.1007/s00018-024-05369-y","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) has successfully established a long-lasting latent infection in humans due to its ability to counteract the host antiviral innate immune response. During coevolution with the host, the virus has evolved various evasion techniques to evade the host's innate immune surveillance. At present, there is still no vaccine available for the prevention and treatment of CMV infection, and the interaction between CMV infection and host antiviral innate immunity is still not well understood. However, ongoing studies will offer new insights into how to treat and prevent CMV infection and its related diseases. Here, we update recent studies on how CMV evades antiviral innate immunity, with a focus on how CMV proteins target and disrupt critical adaptors of antiviral innate immune signaling pathways. This review also discusses some classic intrinsic cellular defences that are crucial to the fight against viral invasion. A comprehensive review of the evasion mechanisms of antiviral innate immunity by CMV will help investigators identify new therapeutic targets and develop vaccines against CMV infection.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"81 1","pages":"341"},"PeriodicalIF":6.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}