Cellular Microbiology最新文献

{"title":"Chlamydia pneumoniae Interferes with Macrophage Differentiation and Cell Cycle Regulation to Promote Its Replication","authors":"Eveliina Taavitsainen-Wahlroos,&nbsp;Ilkka Miettinen,&nbsp;Maarit Ylätalo,&nbsp;Inés Reigada,&nbsp;Kirsi Savijoki,&nbsp;Tuula Anneli Nyman,&nbsp;Leena Hanski","doi":"10.1155/2022/9854449","DOIUrl":"10.1155/2022/9854449","url":null,"abstract":"<div>\u0000 <p><i>Chlamydia pneumoniae</i> is a ubiquitous intracellular bacterium which infects humans via the respiratory route. The tendency of <i>C. pneumoniae</i> to persist in monocytes and macrophages is well known, but the underlying host-chlamydial interactions remain elusive. In this work, we have described changes in macrophage intracellular signaling pathways induced by <i>C. pneumoniae</i> infection. Label-free quantitative proteome analysis and pathway analysis tools were used to identify changes in human THP-1-derived macrophages upon <i>C. pneumoniae</i> CV6 infection. At 48-h postinfection, pathways associated to nuclear factor <i>κ</i>B (NF-<i>κ</i>B) regulation were stressed, while negative regulation on cell cycle control was prominent at both 48 h and 72 h. Upregulation of S100A8 and S100A9 calcium binding proteins, osteopontin, and purine nucleoside hydrolase, laccase domain containing protein 1 (LACC1) underlined the proinflammatory consequences of the infection, while elevated NF-<i>κ</i>B2 levels in infected macrophages indicates interaction with the noncanonical NF-<i>κ</i>B pathway. Infection-induced alteration of cell cycle control was obvious by the downregulation of mini chromosome maintenance (MCM) proteins MCM2-7, and the significance of host cell cycle regulation for <i>C. pneumoniae</i> replication was demonstrated by the ability of a cyclin-dependent kinase (CDK) 4/6 inhibitor Palbociclib to promote <i>C. pneumoniae</i> replication and infectious progeny production. The infection was found to suppress retinoblastoma expression in the macrophages in both protein and mRNA levels, and this change was reverted by treatment with a histone deacetylase inhibitor. The epigenetic suppression of retinoblastoma, along with upregulation of S100A8 and S100A9, indicate host cell changes associated with myeloid-derived suppressor cell (MDSC) phenotype.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/9854449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"93577916","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":"miR-30c Increases the Intracellular Survival of Helicobacter pylori by Inhibiting Autophagy","authors":"Qiuhua Deng,&nbsp;Yifei Xu,&nbsp;Yuanzun Zhong,&nbsp;Liyao Tang,&nbsp;Si Du,&nbsp;Jiongming Yang,&nbsp;Lingping Wu,&nbsp;Shaoju Guo,&nbsp;Bin Huang,&nbsp;Hongying Cao,&nbsp;Ping Huang","doi":"10.1155/2022/4536450","DOIUrl":"10.1155/2022/4536450","url":null,"abstract":"<div>\u0000 <p>Persistent <i>Helicobacter pylori</i> infection causes a variety of gastrointestinal diseases and even gastric cancer. <i>H. pylori</i> invades gastric epithelial cells to survive and proliferate, which is one of the key factors in persistent colonization. A Published study has confirmed that cells can eliminate intracellular <i>H. pylori</i> through xenophagy to maintain intracellular balance. However, a growing body of evidences indicate that <i>H. pylori</i> can inhibit xenophagy by miRNA through regulating the expression of key autophagy-related genes. Through western blot analysis, mRFP-GFP-LC3 transfection assay, and transmission electron microscopy, we found that <i>H. pylori</i> infection obstructed autophagy flux degradation stage in GES-1 cell lines. Gentamicin protection assay confirmed that inhibit xenophagy is benefit for intracellular <i>H. pylori</i> survive. miR-30c-1-3p and miR-30c-5p were upregulated in GES-1 cell lines after infecting with <i>H. pylori</i>, resulting in the negative regulation on xenophagy. Further studies through bioinformatics analysis and dual-luciferase reporter assays confirmed that <i>ATG14</i> and <i>ULK1</i> were the target genes of miR-30c-1-3p and that <i>ATG12</i> was the target gene of miR-30c-5p. The overexpression of miR-30c-1-3p and miR-30c-5p reduces the expression of <i>ATG14</i>, <i>ULK1</i>, and <i>ATG12</i> at mRNA level and also decreased intracellular <i>H. pylori</i> elimination in GES-1 cells. The above results suggested that the inhibition on xenophagy by miR-30c-1-3p and miR-30c-5p through <i>ATG14</i>, <i>ULK1</i>, and <i>ATG12</i> targeting benefitted intracellular <i>H. pylori</i> in the evasion of xenophagy clearance.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/4536450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41958616","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":"Plasmodium berghei-Mediated NRF2 Activation in Infected Hepatocytes Enhances Parasite Survival","authors":"Annina Bindschedler,&nbsp;Jacqueline Schmuckli-Maurer,&nbsp;Rahel Wacker,&nbsp;Nicolas Kramer,&nbsp;Ruth Rehmann,&nbsp;Reto Caldelari,&nbsp;Volker T. Heussler","doi":"10.1155/2022/7647976","DOIUrl":"10.1155/2022/7647976","url":null,"abstract":"<div>\u0000 <p>The protozoan parasite <i>Plasmodium</i>, causative agent of malaria, initially invades and develops in hepatocytes where it resides in a parasitophorous vacuole (PV). A single invaded parasite develops into thousands of daughter parasites. Survival of the host cell is crucial for successful completion of liver stage development. Nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a transcription factor known to induce transcription of cytoprotective genes when activated. Here we show that NRF2 is activated in <i>Plasmodium berghei</i>-infected hepatocytes. We observed that this NRF2 activation depends on PV membrane resident p62 recruiting KEAP1, the negative regulator of NRF2. Disrupting the NRF2 gene results in reduced parasite survival, indicating that NRF2 signaling is an important event for parasite development in hepatocytes. Together, our observations uncovered a novel mechanism of how <i>Plasmodium</i> parasites ensure host cell survival during liver stage development.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/7647976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44930624","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":"Cover Image: Entry of the Varicellovirus Canid herpesvirus 1 into Madin–Darby canine kidney epithelial cells is pH-independent and occurs via a macropinocytosis-like mechanism but without increase in fluid uptake (Cellular Microbiology 12/2021)","authors":"Mohamed Eisa,&nbsp;Hamza Loucif,&nbsp;Julien van Grevenynghe,&nbsp;Angela Pearson","doi":"10.1111/cmi.13401","DOIUrl":"10.1111/cmi.13401","url":null,"abstract":"<p>Confocal micrograph showing <i>Canid herpesvirus 1</i> (red) bound to MDCK cells, and DAPI-stained nuclei (blue). Primary amines of viral glycoproteins were labelled with Alexa Fluor succinimidyl esters 568 dye. For further details, readers are referred to the article by Eisa et al. on p. e13398 of this issue.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cmi.13401","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42370196","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":"Vam6/Vps39/TRAP1-domain proteins influence vacuolar morphology, iron acquisition and virulence in Cryptococcus neoformans","authors":"Guanggan Hu,&nbsp;Erik Bakkeren,&nbsp;Mélissa Caza,&nbsp;Linda Horianopoulos,&nbsp;Eddy Sánchez-León,&nbsp;Melanie Sorensen,&nbsp;Wonhee Jung,&nbsp;James W. Kronstad","doi":"10.1111/cmi.13400","DOIUrl":"10.1111/cmi.13400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The pathogenic fungus <i>Cryptococcus neoformans</i> must overcome iron limitation to cause disease in mammalian hosts. Previously, we reported a screen for insertion mutants with poor growth on haem as the sole iron source. In this study, we characterised one such mutant and found that the defective gene encoded a Vam6/Vps39/TRAP1 domain-containing protein required for robust growth on haem, an important iron source in host tissue. We designated this protein Vps3 based on reciprocal best matches with the corresponding protein in <i>Saccharomyces cerevisiae</i>. <i>C. neoformans</i> encodes a second Vam6/Vps39/TRAP1 domain-containing protein designated Vam6/Vlp1, and we found that this protein is also required for robust growth on haem as well as on inorganic iron sources. This protein is predicted to be a component of the homotypic fusion and vacuole protein sorting complex involved in endocytosis. Further characterisation of the <i>vam6Δ</i> and <i>vps3Δ</i> mutants revealed perturbed trafficking of iron acquisition functions (e.g., the high affinity iron permease Cft1) and impaired processing of the transcription factor Rim101, a regulator of haem and iron acquisition. The <i>vps3Δ</i> and <i>vam6Δ</i> mutants also had pleiotropic phenotypes including loss of virulence in a mouse model of cryptococcosis, reduced virulence factor elaboration and increased susceptibility to stress, indicating pleiotropic roles for Vps3 and Vam6 beyond haem use in <i>C. neoformans</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Two Vam6/Vps39/TRAP1-domain proteins, Vps3 and Vam6, support the growth of <i>Cryptococcus neoformans</i> on haem.</li>\u0000 \u0000 <li>Loss of Vps3 and Vam6 influences the trafficking and expression of iron uptake proteins.</li>\u0000 \u0000 <li>Loss of Vps3 or Vam6 eliminates the ability of <i>C. neoformans</i> to cause disease in a mouse model of cryptococcosis.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39907834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane","authors":"Lili Zhao,&nbsp;Fuwang Chen,&nbsp;Oliver Quitt,&nbsp;Marvin Festag,&nbsp;Marc Ringelhan,&nbsp;Karin Wisskirchen,&nbsp;Julia Festag,&nbsp;Luidmila Yakovleva,&nbsp;Camille Sureau,&nbsp;Felix Bohne,&nbsp;Michaela Aichler,&nbsp;Volker Bruss,&nbsp;Maxim Shevtsov,&nbsp;Maarten van de Klundert,&nbsp;Frank Momburg,&nbsp;Britta S. Möhl,&nbsp;Ulrike Protzer","doi":"10.1111/cmi.13399","DOIUrl":"10.1111/cmi.13399","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication but do not cure HBV, leaving patients at risk to develop hepatocellular carcinoma. Here, we show that HBV envelope proteins (HBs)—besides their integration into endosomal membranes—become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognising a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>HBs become translocated to the plasma membrane.</li>\u0000 \u0000 <li>Novel, recombinant antibody confirmed proper conformation of HBs on the membrane.</li>\u0000 \u0000 <li>HBs provide an interesting target by T-cell-based, potentially curative therapies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cmi.13399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39674410","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":"Chlamydia and HPV induce centrosome amplification in the host cell through additive mechanisms","authors":"Kevin Wang,&nbsp;Karissa J. Muñoz,&nbsp;Ming Tan,&nbsp;Christine Sütterlin","doi":"10.1111/cmi.13397","DOIUrl":"10.1111/cmi.13397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Based on epidemiology studies, <i>Chlamydia trachomatis</i> has been proposed as a co-factor for human papillomavirus (HPV) in the development of cervical cancer. These two intracellular pathogens have been independently reported to induce the production of extra centrosomes, or centrosome amplification, which is a hallmark of cancer cells. We developed a cell culture model to systematically measure the individual and combined effects of <i>Chlamydia</i> and HPV on the centrosome in the same host cell. We found that <i>C. trachomatis</i> caused centrosome amplification in a greater proportion of cells than HPV and that the effects of the two pathogens on the centrosome were additive. Furthermore, centrosome amplification induced by <i>Chlamydia</i>, but not by HPV, strongly correlated with multinucleation and required progression through mitosis. Our results suggest that <i>C. trachomatis</i> and HPV induce centrosome amplification through different mechanisms, with the chlamydial effect being largely due to a failure in cytokinesis that also results in multinucleation. Our findings provide support for <i>C. trachomatis</i> as a co-factor for HPV in carcinogenesis and offer mechanistic insights into how two infectious agents may cooperate to promote cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <p>• <i>Chlamydia</i> and HPV induce centrosome amplification in an additive manner.</p>\u0000 \u0000 <p>• <i>Chlamydia</i>-induced centrosome amplification is linked to host cell multinucleation.</p>\u0000 \u0000 <p>• <i>Chlamydia</i>-induced centrosome amplification requires cell cycle progression.</p>\u0000 \u0000 <p>• <i>Chlamydia</i> and HPV cause centrosome amplification through different mechanisms.</p>\u0000 \u0000 <p>• This study supports <i>Chlamydia</i> as a co-factor for HPV in carcinogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39842219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Entry of the Varicellovirus Canid herpesvirus 1 into Madin–Darby canine kidney epithelial cells is pH-independent and occurs via a macropinocytosis-like mechanism but without increase in fluid uptake","authors":"Mohamed Eisa,&nbsp;Hamza Loucif,&nbsp;Julien van Grevenynghe,&nbsp;Angela Pearson","doi":"10.1111/cmi.13398","DOIUrl":"10.1111/cmi.13398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p><i>Canid herpesvirus</i> 1 (CHV-1) is a <i>Varicellovirus</i> that causes self-limiting infections in adult dogs but morbidity and mortality in puppies. Using a multipronged approach, we discovered the CHV-1 entry pathway into Madin–Darby canine kidney (MDCK) epithelial cells. We found that CHV-1 triggered extensive host cell membrane lamellipodial ruffling and rapid internalisation of virions in large, uncoated vacuoles, suggestive of macropinocytosis. Treatment with inhibitors targeting key macropinocytosis factors, including inhibitors of Na⁺/H⁺ exchangers, F-actin, myosin light-chain kinase, protein kinase C, p21-activated kinase, phosphatidylinositol-3-kinase and focal adhesion kinase, significantly reduced viral replication. Moreover, the effect was restricted to exposure to the inhibitors early in infection, confirming a role for the macropinocytic machinery during entry. The profile of inhibitors also suggested a role for signalling via integrins and receptor tyrosine kinases in viral entry. In contrast, inhibitors of clathrin, caveolin, microtubules and endosomal acidification did not affect CHV-1 entry into MDCK cells. We found that the virus colocalised with the fluid-phase uptake marker dextran; however, surprisingly, CHV-1 infection did not enhance the uptake of dextran. Thus, our results indicate that CHV-1 uses a macropinocytosis-like, pH-independent entry pathway into MDCK cells, which nevertheless is not based on stimulation of fluid uptake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>CHV-1 enters epithelial cells via a macropinocytosis-like mechanism.</li>\u0000 \u0000 <li>CHV-1 induces extensive lamellipodial ruffling.</li>\u0000 \u0000 <li>CHV-1 entry into MDCK cells is pH-independent.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39557986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image: The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis (Cellular Microbiology 11/2021)","authors":"Silvia Radosa,&nbsp;Jakob L. Sprague,&nbsp;Siu-Hin Lau,&nbsp;Renáta Tóth,&nbsp;Jörg Linde,&nbsp;Thomas Krüger,&nbsp;Marcel Sprenger,&nbsp;Lydia Kasper,&nbsp;Martin Westermann,&nbsp;Olaf Kniemeyer,&nbsp;Bernhard Hube,&nbsp;Axel A. Brakhage,&nbsp;Attila Gácser,&nbsp;Falk Hillmann","doi":"10.1111/cmi.13396","DOIUrl":"10.1111/cmi.13396","url":null,"abstract":"<p>The fungivorous amoeba <i>Protostelium aurantium</i> feeds on a wide range of fungal species. The image shows amoebae digesting GFP-expressing cells of the human pathogenic yeast <i>Candida parapsilosis</i>. For further details, readers are referred to the article by Radosa et al. on p. e13389 of this issue.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cmi.13396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41610318","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":"Dengue virus replication enhances labile zinc pools by modulation of ZIP8","authors":"Aleksha Panwar,&nbsp;Jigme Wangchuk,&nbsp;Meenakshi Kar,&nbsp;Rakesh Lodha,&nbsp;Guruprasad R. Medigeshi","doi":"10.1111/cmi.13395","DOIUrl":"10.1111/cmi.13395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Zinc-dependent viral proteins rely on intracellular zinc homeostasis for successful completion of infectious life-cycle. Here, we report that the intracellular labile zinc levels were elevated at early stages of dengue virus (DENV) infection in hepatic cells and this increase in free zinc was abolished in cells infected with UV-inactivated virus or with a DENV replication inhibitor implicating a role for zinc homeostasis in viral RNA replication. This change in free zinc was mediated by zinc transporter, ZIP8, as siRNA-mediated knockdown of ZIP8 resulted in abrogation of increase in free zinc levels leading to significant reduction in DENV titers suggesting a crucial role for ZIP8 in early stages of DENV replication. Furthermore, elevated free zinc levels correlated with high copy numbers of dengue genome in peripheral blood leukocytes obtained from dengue patients compared to healthy controls suggesting a critical role for zinc homeostasis in dengue infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Dengue virus utilises cellular zinc homeostasis during replication of its RNA.</li>\u0000 \u0000 <li>ZIP8 upregulates free zinc levels during dengue virus replication.</li>\u0000 \u0000 <li>Enhanced viremia associates with elevated intracellular free zinc in dengue.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39518423","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}