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Cell Host & Microbe

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https://www.readbyqxmd.com/read/28238623/salmonella-enterica-remodels-the-host-cell-endosomal-system-for-efficient-intravacuolar-nutrition
#1
Viktoria Liss, A Leoni Swart, Alexander Kehl, Natascha Hermanns, Yuying Zhang, Deepak Chikkaballi, Nathalie Böhles, Jörg Deiwick, Michael Hensel
Salmonella enterica is a facultative intracellular pathogen that survives and proliferates in the Salmonella-containing vacuole (SCV), yet how these vacuolar bacteria acquire nutrition remains to be determined. Intracellular Salmonella convert the host endosomal system into an extensive network of interconnected tubular vesicles, of which Salmonella-induced filaments (SIFs) are the most prominent. We found that membranes and lumen of SIFs and SCVs form a continuum, giving vacuolar Salmonella access to various types of endocytosed material...
February 21, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28238624/biochemical-basis-for-increased-activity-of-ebola-glycoprotein-in-the-2013-16-epidemic
#2
May K Wang, Sun-Young Lim, Soo Mi Lee, James M Cunningham
Ebola virus (EBOV) infection is characterized by sporadic outbreaks caused by zoonotic transmission. Fixed changes in amino acid sequence, such as A82V in the EBOV glycoprotein (GP) that occurred early in the 2013-16 epidemic, are suspected to confer a selective advantage to the virus. We used biochemical assays of GP function to show that A82V, as well as a polymorphism in residue 544 identified in other outbreaks, enhances infection by decreasing the threshold for activation of membrane fusion activity triggered by the host factors cathepsin B and Niemann-Pick C1...
February 18, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28216251/sars-cov-encoded-small-rnas-contribute-to-infection-associated-lung-pathology
#3
Lucía Morales, Juan Carlos Oliveros, Raúl Fernandez-Delgado, Benjamin Robert tenOever, Luis Enjuanes, Isabel Sola
Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18-22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication...
February 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407488/the-matrix-protein-of-human-parainfluenza-virus-type-3-induces-mitophagy-that-suppresses-interferon-responses
#4
Binbin Ding, Linliang Zhang, Zhifei Li, Yi Zhong, Qiaopeng Tang, Yali Qin, Mingzhou Chen
Mitophagy is a form of autophagy that selectively removes damaged mitochondria. Impaired mitochondria can be tagged by the kinase PINK1, which triggers recruitment of the E3-ubiquitin ligase Parkin and subsequent mitochondrial sequestration within autophagosomes. We previously found that human parainfluenza virus type 3 (HPIV3) infection induces autophagy, but the type and mechanisms of autophagy induction remain unknown. Here, we show that matrix protein (M) of HPIV3 translocates to mitochondria and interacts with Tu translation elongation factor mitochondrial (TUFM)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407487/matching-nlr-immune-receptors-to-autoimmunity-in-camta3-mutants-using-antimorphic-nlr-alleles
#5
Signe Lolle, Christiaan Greeff, Klaus Petersen, Milena Roux, Michael Krogh Jensen, Simon Bressendorff, Eleazar Rodriguez, Kenneth Sømark, John Mundy, Morten Petersen
To establish infection, pathogens deploy effectors to modify or remove host proteins. Plant immune receptors with nucleotide-binding, leucine-rich repeat domains (NLRs) detect these modifications and trigger immunity. Plant NLRs thus guard host "guardees." A corollary is that autoimmunity may result from inappropriate NLR activation because mutations in plant guardees could trigger corresponding NLR guards. To explore these hypotheses, we expressed 108 dominant-negative (DN) Arabidopsis NLRs in various lesion mimic mutants, including camta3, which exhibits autoimmunity...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407486/transcriptional-elongation-of-hsv-immediate-early-genes-by-the-super-elongation-complex-drives-lytic-infection-and-reactivation-from-latency
#6
Roberto Alfonso-Dunn, Anne-Marie W Turner, Pierre M Jean Beltran, Jesse H Arbuckle, Hanna G Budayeva, Ileana M Cristea, Thomas M Kristie
The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407485/defective-hiv-1-proviruses-are-expressed-and-can-be-recognized-by-cytotoxic-t-lymphocytes-which-shape-the-proviral-landscape
#7
Ross A Pollack, R Brad Jones, Mihaela Pertea, Katherine M Bruner, Alyssa R Martin, Allison S Thomas, Adam A Capoferri, Subul A Beg, Szu-Han Huang, Sara Karandish, Haiping Hao, Eitan Halper-Stromberg, Patrick C Yong, Colin Kovacs, Erika Benko, Robert F Siliciano, Ya-Chi Ho
Despite antiretroviral therapy, HIV-1 persists in memory CD4(+) T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs)...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407484/autoreactive-t-cells-and-chronic-fungal-infection-drive-esophageal-carcinogenesis
#8
Feng Zhu, Jami Willette-Brown, Na-Young Song, Dakshayani Lomada, Yongmei Song, Liyan Xue, Zane Gray, Zitong Zhao, Sean R Davis, Zhonghe Sun, Peilin Zhang, Xiaolin Wu, Qimin Zhan, Ellen R Richie, Yinling Hu
Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell-driven autoimmune disease caused by impaired central tolerance, are susceptible to chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop APECED-like phenotypes, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407483/age-associated-microbial-dysbiosis-promotes-intestinal-permeability-systemic-inflammation-and-macrophage-dysfunction
#9
Netusha Thevaranjan, Alicja Puchta, Christian Schulz, Avee Naidoo, J C Szamosi, Chris P Verschoor, Dessi Loukov, Louis P Schenck, Jennifer Jury, Kevin P Foley, Jonathan D Schertzer, Maggie J Larché, Donald J Davidson, Elena F Verdú, Michael G Surette, Dawn M E Bowdish
Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity. Co-housing germ-free mice with old, but not young, conventionally raised mice increases pro-inflammatory cytokines in the blood...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407482/salmonella-typhimurium-diarrhea-reveals-basic-principles-of-enteropathogen-infection-and-disease-promoted-dna-exchange
#10
REVIEW
Sandra Y Wotzka, Bidong D Nguyen, Wolf-Dietrich Hardt
Despite decades of research, efficient therapies for most enteropathogenic bacteria are still lacking. In this review, we focus on Salmonella enterica Typhimurium (S. Typhimurium), a frequent cause of acute, self-limiting food-borne diarrhea and a model that has revealed key principles of enteropathogen infection. We review the steps of gut infection and the mucosal innate-immune defenses limiting pathogen burdens, and we discuss how inflammation boosts gut luminal S. Typhimurium growth. We also discuss how S...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407481/the-gut-microbiome-connecting-spatial-organization-to-function
#11
REVIEW
Carolina Tropini, Kristen A Earle, Kerwyn Casey Huang, Justin L Sonnenburg
The first rudimentary evidence that the human body harbors a microbiota hinted at the complexity of host-associated microbial ecosystems. Now, almost 400 years later, a renaissance in the study of microbiota spatial organization, driven by coincident revolutions in imaging and sequencing technologies, is revealing functional relationships between biogeography and health, particularly in the vertebrate gut. In this Review, we present our current understanding of principles governing the localization of intestinal bacteria, and spatial relationships between bacteria and their hosts...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407480/the-landscape-ecology-and-microbiota-of-the-human-nose-mouth-and-throat
#12
REVIEW
Diana M Proctor, David A Relman
Landscape ecology examines the relationships between the spatial arrangement of different landforms and the processes that give rise to spatial and temporal patterns in local community structure. The spatial ecology of the microbial communities that inhabit the human body-in particular, those of the nose, mouth, and throat-deserves greater attention. Important questions include what defines the size of a population (i.e., "patch") in a given body site, what defines the boundaries of distinct patches within a single body site, and where and over what spatial scales within a body site are gradients detected...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407479/living-in-peace-host-microbiota-mutualism-in-the-skin
#13
Daniel J Campbell, Meghan A Koch
Commensal microbes colonize the skin where they promote immune development and prevent infection without inducing damaging inflammatory responses. In this issue of Cell Host & Microbe, Scharschmidt et al. (2017) show that during hair follicle development, commensals induce regulatory T cell migration to the skin to ensure cutaneous homeostasis.
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407478/breaking-down-walls-microbiota-and-the-aging-gut
#14
Erin S Keebaugh, William W Ja
A range of animal species show increased inflammation with age. In this issue of Cell Host & Microbe, Thevaranjan et al. (2017) reveal that heightened inflammation is associated with deregulation of homeostatic interactions between intestinal microbes and the aging host.
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28407477/a-riptide-protects-neurons-from-infection
#15
Ryan P Gilley, William J Kaiser
RIPK3 and RIPK1 limit virus spread by executing either apoptotic or necroptotic cell death in response to infection. In a recent issue of Cell, Daniels et al. (2017) unveil an unexpected cell death-independent requirement of RIP kinase activity in coordinating neuroinflammation, restricting West Nile virus pathogenesis in neurons.
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28366509/anaerobic-bacterial-fermentation-products-increase-tuberculosis-risk-in-antiretroviral-drug-treated-hiv-patients
#16
Leopoldo N Segal, Jose C Clemente, Yonghua Li, Chunhai Ruan, Jane Cao, Mauricio Danckers, Alison Morris, Sarah Tapyrik, Benjamin G Wu, Philip Diaz, Gregory Calligaro, Rodney Dawson, Richard N van Zyl-Smit, Keertan Dheda, William N Rom, Michael D Weiden
Despite the immune-reconstitution with antiretroviral therapy (ART), HIV-infected individuals remain highly susceptible to tuberculosis (TB) and have an enrichment of oral anaerobes in the lung. Products of bacterial anaerobic metabolism, like butyrate and other short-chain fatty acids (SCFAs), induce regulatory T cells (Tregs). We tested whether SCFAs contribute to poor TB control in a longitudinal cohort of ART-treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28343820/commensal-microbes-and-hair-follicle-morphogenesis-coordinately-drive-treg-migration-into-neonatal-skin
#17
Tiffany C Scharschmidt, Kimberly S Vasquez, Mariela L Pauli, Elizabeth G Leitner, Kevin Chu, Hong-An Truong, Margaret M Lowe, Robert Sanchez Rodriguez, Niwa Ali, Zoltan G Laszik, Justin L Sonnenburg, Sarah E Millar, Michael D Rosenblum
Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28279348/structure-guided-identification-of-a-family-of-dual-receptor-binding-pfemp1-that-is-associated-with-cerebral-malaria
#18
Frank Lennartz, Yvonne Adams, Anja Bengtsson, Rebecca W Olsen, Louise Turner, Nicaise T Ndam, Gertrude Ecklu-Mensah, Azizath Moussiliou, Michael F Ofori, Benoit Gamain, John P Lusingu, Jens E V Petersen, Christian W Wang, Sofia Nunes-Silva, Jakob S Jespersen, Clinton K Y Lau, Thor G Theander, Thomas Lavstsen, Lars Hviid, Matthew K Higgins, Anja T R Jensen
Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria, a binding phenotype linked to its symptoms has not been identified. Here, we used structural biology to determine how a group of PfEMP1 proteins interacts with intercellular adhesion molecule 1 (ICAM-1), allowing us to predict binders from a specific sequence motif alone...
March 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28279347/helicobacter-pylori-adapts-to-chronic-infection-and-gastric-disease-via-ph-responsive-baba-mediated-adherence
#19
Jeanna A Bugaytsova, Oscar Björnham, Yevgen A Chernov, Pär Gideonsson, Sara Henriksson, Melissa Mendez, Rolf Sjöström, Jafar Mahdavi, Anna Shevtsova, Dag Ilver, Kristof Moonens, Macarena P Quintana-Hayashi, Roman Moskalenko, Christopher Aisenbrey, Göran Bylund, Alexej Schmidt, Anna Åberg, Kristoffer Brännström, Verena Königer, Susanne Vikström, Lena Rakhimova, Anders Hofer, Johan Ögren, Hui Liu, Matthew D Goldman, Jeannette M Whitmire, Jörgen Ådén, Justine Younson, Charles G Kelly, Robert H Gilman, Abhijit Chowdhury, Asish K Mukhopadhyay, G Balakrish Nair, Konstantinos S Papadakos, Beatriz Martinez-Gonzalez, Dionyssios N Sgouras, Lars Engstrand, Magnus Unemo, Dan Danielsson, Sebastian Suerbaum, Stefan Oscarson, Ludmilla A Morozova-Roche, Anders Olofsson, Gerhard Gröbner, Jan Holgersson, Anders Esberg, Nicklas Strömberg, Maréne Landström, Angela M Eldridge, Brett A Chromy, Lori M Hansen, Jay V Solnick, Sara K Lindén, Rainer Haas, Andre Dubois, D Scott Merrell, Staffan Schedin, Han Remaut, Anna Arnqvist, Douglas E Berg, Thomas Borén
The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time...
March 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28279346/betacoronavirus-adaptation-to-humans-involved-progressive-loss-of-hemagglutinin-esterase-lectin-activity
#20
Mark J G Bakkers, Yifei Lang, Louris J Feitsma, Ruben J G Hulswit, Stefanie A H de Poot, Arno L W van Vliet, Irina Margine, Jolanda D F de Groot-Mijnes, Frank J M van Kuppeveld, Martijn A Langereis, Eric G Huizinga, Raoul J de Groot
Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43's introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation of mutations in the HE lectin domain...
March 8, 2017: Cell Host & Microbe
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