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Cell Host & Microbe

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
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
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
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
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
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
Lulan Wang, Su-Yang Liu, Hsiang-Wen Chen, Juan Xu, Maxime Chapon, Tao Zhang, Fan Zhou, Yao E Wang, Natalie Quanquin, Guiqin Wang, Xiaoli Tian, Zhanlong He, Longding Liu, Wenhai Yu, David Jesse Sanchez, Yuying Liang, Taijiao Jiang, Robert Modlin, Barry R Bloom, Qihan Li, Jane C Deng, Paul Zhou, F Xiao-Feng Qin, Genhong Cheng
New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain...
March 8, 2017: Cell Host & Microbe
Géraldine Engels, Alexandra Maximiliane Hierweger, Julia Hoffmann, René Thieme, Swantje Thiele, Stephanie Bertram, Carola Dreier, Patricia Resa-Infante, Henning Jacobsen, Kristin Thiele, Malik Alawi, Daniela Indenbirken, Adam Grundhoff, Svenja Siebels, Nicole Fischer, Violeta Stojanovska, Damián Muzzio, Federico Jensen, Khalil Karimi, Hans-Willi Mittrücker, Petra Clara Arck, Gülsah Gabriel
Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8(+) T cells into the lung...
March 8, 2017: Cell Host & Microbe
Masanori Hatakeyama
Helicobacter pylori survives in the hostile acidic environment of the stomach through extensive adaptation. In this issue of Cell Host & Microbe, Bugaytsova et al. (2017) report an acid-responsive, reversible adherence of H. pylori BabA to the gastric mucosa, the strength of which is tuned by dynamic BabA adaptation.
March 8, 2017: Cell Host & Microbe
Christopher F Basler
Recent studies demonstrate that the Ebola virus glycoprotein (GP) acquired an A82V change during the West Africa epidemic and that this change altered the capacity of GP to be activated by host factors, enhancing infection of human cells. How this may alter the outcome of disease remains to be determined.
March 8, 2017: Cell Host & Microbe
Stylianos Bournazos, Jeffrey V Ravetch
Live attenuated vaccines are more immunogenic and have the capacity to elicit long-lasting immune responses. In two recent studies, Wang et al. (2017) and Si et al. (2016) describe strategies for the generation of live attenuated influenza viruses, which elicited robust humoral, mucosal, and cellular immunity against diverse virus strains.
March 8, 2017: Cell Host & Microbe
Shee-Mei Lok
Dengue hemorrhagic fever is shown to correlate with secondary infection with a virus serotype different from the previous infection. However, only a small fraction of secondary infections leads to hemorrhagic fever. A recent Science paper suggests that the fucosylation state and isotype of IgGs elicited in patients may enhance disease severity.
March 8, 2017: Cell Host & Microbe
Jane M Carlton, Steven A Sullivan
The Plasmodium genus has evolved over time and across hosts, complexifying our understanding of malaria. In a recent Nature paper, Rutledge et al. (2017) describe the genome sequences of three major human malaria parasite species, providing insight into Plasmodium evolution and raising the question of how many species there are.
March 8, 2017: Cell Host & Microbe
Petter Brodin
Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.
March 8, 2017: Cell Host & Microbe
Helen M Lazear
The 2015 emergence of Zika virus (ZIKV) in the Americas brought new attention to this previously obscure virus. Experimental model systems have been instrumental in rapidly advancing our understanding of ZIKV pathogenesis. Here, Lazear looks back on the events leading to the development of the ZIKV mouse model reported in Cell Host & Microbe.
March 8, 2017: Cell Host & Microbe
Dirk Gevers, Subra Kugathasan, Dan Knights, Aleksandar D Kostic, Rob Knight, Ramnik J Xavier
Our 2014 study published in Cell Host & Microbe, "The Treatment-Naive Microbiome in New-Onset Crohn's Disease," was designed to improve our understanding of the microbiome's role in Crohn's disease by studying a unique, well-suited cohort and sample set. This commentary provides a hindsight perspective of this original study as well as future outlook.
March 8, 2017: Cell Host & Microbe
Mihai G Netea, Jos W M van der Meer
The innate arm of the immune system has generally been regarded as primitive and non-specific and, in contrast to adaptive immunity, not to possess memory. Here we review the growing body of evidence that innate immunity has an important capacity to adapt, a de facto innate immune memory (also termed trained immunity), and this provides broad protection against infections.
March 8, 2017: Cell Host & Microbe
Jake Baum, Dave Richard, David T Riglar
It is only in the last decade that sub-cellular resolution of red cell invasion by the malaria parasite Plasmodium falciparum has been possible. Here we look back on the development of methodologies that led to this possibility and the subsequent advancements made in understanding this key event in malaria disease.
March 8, 2017: Cell Host & Microbe
Jason W Upton, William J Kaiser
Interrogation of murine cytomegalovirus (MCMV)-encoded cell-death suppressors revealed that necroptosis functions as a trap door to eliminate virally infected cells. This crucial host defense pathway is orchestrated by the sensing of infection by DAI/ZBP-1, engagement of the kinase RIPK3, and subsequent membrane permeablization by the pseudokinase MLKL.
March 8, 2017: Cell Host & Microbe
Rachel D Hood, S Brook Peterson, Joseph D Mougous
Specialized secretion systems are infamous for their contribution to host-pathogen interactions. Our discovery that the type VI secretion system delivers toxins between bacterial cells has broadened our understanding of how both pathogens and non-pathogens interact with one another, whether within or outside of the host.
March 8, 2017: Cell Host & Microbe
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