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PLoS Pathogens

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https://www.readbyqxmd.com/read/28651017/crystal-structure-of-middle-east-respiratory-syndrome-coronavirus-helicase
#1
Wei Hao, Justyna Aleksandra Wojdyla, Rong Zhao, Ruiyun Han, Rajat Das, Ivan Zlatev, Muthiah Manoharan, Meitian Wang, Sheng Cui
Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28651010/macrophages-but-not-neutrophils-are-critical-for-proliferation-of-burkholderia-cenocepacia-and-ensuing-host-damaging-inflammation
#2
Jennifer Mesureur, Joana R Feliciano, Nelly Wagner, Margarida C Gomes, Lili Zhang, Monica Blanco-Gonzalez, Michiel van der Vaart, David O'Callaghan, Annemarie H Meijer, Annette C Vergunst
Bacteria of the Burkholderia cepacia complex (Bcc) can cause devastating pulmonary infections in cystic fibrosis (CF) patients, yet the precise mechanisms underlying inflammation, recurrent exacerbations and transition from chronic stages to acute infection and septicemia are not known. Bcc bacteria are generally believed to have a predominant extracellular biofilm life style in infected CF lungs, similar to Pseudomonas aeruginosa, but this has been challenged by clinical observations which show Bcc bacteria predominantly in alveolar macrophages...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28651004/a-human-endogenous-retrovirus-derived-gene-that-can-contribute-to-oncogenesis-by-activating-the-erk-pathway-and-inducing-migration-and-invasion
#3
Cécile Lemaître, Jhen Tsang, Caroline Bireau, Thierry Heidmann, Marie Dewannieux
Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28650995/septins-restrict-inflammation-and-protect-zebrafish-larvae-from-shigella-infection
#4
Maria J Mazon-Moya, Alexandra R Willis, Vincenzo Torraca, Laurent Boucontet, Avinash R Shenoy, Emma Colucci-Guyon, Serge Mostowy
Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human colonic epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28650977/leishmania-donovani-resides-in-modified-early-endosomes-by-upregulating-rab5a-expression-via-the-downregulation-of-mir-494
#5
Jitender Kumar Verma, Ruchir Rastogi, Amitabha Mukhopadhyay
Several intracellular pathogens arrest the phagosome maturation in the host cells to avoid transport to lysosomes. In contrast, the Leishmania containing parasitophorous vacuole (PV) is shown to recruit lysosomal markers and thus Leishmania is postulated to be residing in the phagolysosomes in macrophages. Here, we report that Leishmania donovani specifically upregulates the expression of Rab5a by degrading c-Jun via their metalloprotease gp63 to downregulate the expression of miR-494 in THP-1 differentiated human macrophages...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28644872/helicobacter-pylori-gene-silencing-in-vivo-demonstrates-urease-is-essential-for-chronic-infection
#6
Aleksandra W Debowski, Senta M Walton, Eng-Guan Chua, Alfred Chin-Yen Tay, Tingting Liao, Binit Lamichhane, Robyn Himbeck, Keith A Stubbs, Barry J Marshall, Alma Fulurija, Mohammed Benghezal
Helicobacter pylori infection causes chronic active gastritis that after many years of infection can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the gastric environment and a key adaptation is the virulence factor urease. Although widely postulated, the requirement of urease expression for persistent infection has not been elucidated experimentally as conventional urease knockout mutants are incapable of colonization. To overcome this constraint, conditional H...
June 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28644867/host-derived-apolipoproteins-play-comparable-roles-with-viral-secretory-proteins-erns-and-ns1-in-the-infectious-particle-formation-of-flaviviridae
#7
Takasuke Fukuhara, Tomokazu Tamura, Chikako Ono, Mai Shiokawa, Hiroyuki Mori, Kentaro Uemura, Satomi Yamamoto, Takeshi Kurihara, Toru Okamoto, Ryosuke Suzuki, Kentaro Yoshii, Takeshi Kurosu, Manabu Igarashi, Hiroshi Aoki, Yoshihiro Sakoda, Yoshiharu Matsuura
Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane...
June 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640917/human-hantavirus-infection-elicits-pronounced-redistribution-of-mononuclear-phagocytes-in-peripheral-blood-and-airways
#8
Saskia Scholz, Faezzah Baharom, Gregory Rankin, Kimia T Maleki, Shawon Gupta, Sindhu Vangeti, Jamshid Pourazar, Andrea Discacciati, Jonas Höijer, Matteo Bottai, Niklas K Björkström, Johan Rasmuson, Magnus Evander, Anders Blomberg, Hans-Gustaf Ljunggren, Jonas Klingström, Clas Ahlm, Anna Smed-Sörensen
Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis...
June 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640879/dual-targeting-of-a-virus-movement-protein-to-er-and-plasma-membrane-subdomains-is-essential-for-plasmodesmata-localization
#9
Kazuya Ishikawa, Masayoshi Hashimoto, Akira Yusa, Hiroaki Koinuma, Yugo Kitazawa, Osamu Netsu, Yasuyuki Yamaji, Shigetou Namba
Plant virus movement proteins (MPs) localize to plasmodesmata (PD) to facilitate virus cell-to-cell movement. Numerous studies have suggested that MPs use a pathway either through the ER or through the plasma membrane (PM). Furthermore, recent studies reported that ER-PM contact sites and PM microdomains, which are subdomains found in the ER and PM, are involved in virus cell-to-cell movement. However, functional relationship of these subdomains in MP traffic to PD has not been described previously. We demonstrate here the intracellular trafficking of fig mosaic virus MP (MPFMV) using live cell imaging, focusing on its ER-directing signal peptide (SPFMV)...
June 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28632755/potassium-is-a-key-signal-in-host-microbiome-dysbiosis-in-periodontitis
#10
Susan Yost, Ana E Duran-Pinedo, Keerthana Krishnan, Jorge Frias-Lopez
Dysbiosis, or the imbalance in the structural and/or functional properties of the microbiome, is at the origin of important infectious inflammatory diseases such as inflammatory bowel disease (IBD) and periodontal disease. Periodontitis is a polymicrobial inflammatory disease that affects a large proportion of the world's population and has been associated with a wide variety of systemic health conditions, such as diabetes, cardiovascular and respiratory diseases. Dysbiosis has been identified as a key element in the development of the disease...
June 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628666/the-effector-avrrxo1-phosphorylates-nad-in-planta
#11
Teja Shidore, Corey D Broeckling, Jay S Kirkwood, John J Long, Jiamin Miao, Bingyu Zhao, Jan E Leach, Lindsay R Triplett
Gram-negative bacterial pathogens of plants and animals employ type III secreted effectors to suppress innate immunity. Most characterized effectors work through modification of host proteins or transcriptional regulators, although a few are known to modify small molecule targets. The Xanthomonas type III secreted avirulence factor AvrRxo1 is a structural homolog of the zeta toxin family of sugar-nucleotide kinases that suppresses bacterial growth. AvrRxo1 was recently reported to phosphorylate the central metabolite and signaling molecule NAD in vitro, suggesting that the effector might enhance bacterial virulence on plants through manipulation of primary metabolic pathways...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628655/moend3-regulates-appressorium-formation-and-virulence-through-mediating-endocytosis-in-rice-blast-fungus-magnaporthe-oryzae
#12
Xiao Li, Chuyun Gao, Lianwei Li, Muxing Liu, Ziyi Yin, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Zhengguang Zhang
Eukaryotic cells respond to environmental stimuli when cell surface receptors are bound by environmental ligands. The binding initiates a signal transduction cascade that results in the appropriate intracellular responses. Studies have shown that endocytosis is critical for receptor internalization and signaling activation. In the rice blast fungus Magnaporthe oryzae, a non-canonical G-protein coupled receptor, Pth11, and membrane sensors MoMsb2 and MoSho1 are thought to function upstream of G-protein/cAMP signaling and the Pmk1 MAPK pathway to regulate appressorium formation and pathogenesis...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628654/the-apah-like-phosphatase-tbalph1-is-the-major-mrna-decapping-enzyme-of-trypanosomes
#13
Susanne Kramer
5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628650/the-human-cytomegalovirus-glycoprotein-pul11-acts-via-cd45-to-induce-t-cell-il-10-secretion
#14
Jasmin Zischke, Panagiota Mamareli, Claudia Pokoyski, Ildar Gabaev, Sabine Buyny, Roland Jacobs, Christine S Falk, Matthias Lochner, Tim Sparwasser, Thomas F Schulz, Penelope C Kay-Fedorov
Human Cytomegalovirus (HCMV) is a widespread pathogen, infection with which can cause severe disease for immunocompromised individuals. The complex changes wrought on the host's immune system during both productive and latent HCMV infection are well known. Infected cells are masked and manipulated and uninfected immune cells are also affected; peripheral blood mononuclear cell (PBMC) proliferation is reduced and cytokine profiles altered. Levels increase of the anti-inflammatory cytokine IL-10, which may be important for the establishment of HCMV infections and is required for the development of high viral titres by murine cytomegalovirus...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28628648/the-adenovirus-major-core-protein-vii-is-dispensable-for-virion-assembly-but-is-essential-for-lytic-infection
#15
Philomena Ostapchuk, Maarit Suomalainen, Yueting Zheng, Karin Boucke, Urs F Greber, Patrick Hearing
The Adenovirus (Ad) genome within the capsid is tightly associated with a virus-encoded, histone-like core protein-protein VII. Two other Ad core proteins, V and X/μ, also are located within the virion and are loosely associated with viral DNA. Core protein VII remains associated with the Ad genome during the early phase of infection. It is not known if naked Ad DNA is packaged into the capsid, as with dsDNA bacteriophage and herpesviruses, followed by the encapsidation of viral core proteins, or if a unique packaging mechanism exists with Ad where a DNA-protein complex is simultaneously packaged into the virion...
June 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28622386/alpha-defensin-dependent-enhancement-of-enteric-viral-infection
#16
Sarah S Wilson, Beth A Bromme, Mayumi K Holly, Mayim E Wiens, Anshu P Gounder, Youngmee Sul, Jason G Smith
The small intestinal epithelium produces numerous antimicrobial peptides and proteins, including abundant enteric α-defensins. Although they most commonly function as potent antivirals in cell culture, enteric α-defensins have also been shown to enhance some viral infections in vitro. Efforts to determine the physiologic relevance of enhanced infection have been limited by the absence of a suitable cell culture system. To address this issue, here we use primary stem cell-derived small intestinal enteroids to examine the impact of naturally secreted α-defensins on infection by the enteric mouse pathogen, mouse adenovirus 2 (MAdV-2)...
June 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28622363/acyloxyacyl-hydrolase-promotes-the-resolution-of-lipopolysaccharide-induced-acute-lung-injury
#17
Benkun Zou, Wei Jiang, Han Han, Jing Li, Weiying Mao, Zihui Tang, Qian Yang, Guojun Qian, Jing Qian, Wenjiao Zeng, Jie Gu, Tianqing Chu, Ning Zhu, Wenhong Zhang, Dapeng Yan, Rui He, Yiwei Chu, Mingfang Lu
Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS)...
June 16, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28617871/hypoxia-inducible-factor-1%C3%AE-plays-roles-in-epstein-barr-virus-s-natural-life-cycle-and-tumorigenesis-by-inducing-lytic-infection-through-direct-binding-to-the-immediate-early-bzlf1-gene-promoter
#18
Richard J Kraus, Xianming Yu, Blue-Leaf A Cordes, Saraniya Sathiamoorthi, Tawin Iempridee, Dhananjay M Nawandar, Shidong Ma, James C Romero-Masters, Kyle G McChesney, Zhen Lin, Kathleen R Makielski, Denis L Lee, Paul F Lambert, Eric C Johannsen, Shannon C Kenney, Janet E Mertz
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens...
June 15, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28481926/delineating-morbillivirus-entry-dissemination-and-airborne-transmission-by-studying-in-vivo-competition-of-multicolor-canine-distemper-viruses-in-ferrets
#19
Rory D de Vries, Martin Ludlow, Alwin de Jong, Linda J Rennick, R Joyce Verburgh, Geert van Amerongen, Debby van Riel, Peter R W A van Run, Sander Herfst, Thijs Kuiken, Ron A M Fouchier, Albert D M E Osterhaus, Rik L de Swart, W Paul Duprex
Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (CDV) expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo)...
May 8, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28475648/hiv-1-competition-experiments-in-humanized-mice-show-that-apobec3h-imposes-selective-pressure-and-promotes-virus-adaptation
#20
Yusuke Nakano, Naoko Misawa, Guillermo Juarez-Fernandez, Miyu Moriwaki, Shinji Nakaoka, Takaaki Funo, Eri Yamada, Andrew Soper, Rokusuke Yoshikawa, Diako Ebrahimi, Yuuya Tachiki, Shingo Iwami, Reuben S Harris, Yoshio Koyanagi, Kei Sato
APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo...
May 5, 2017: PLoS Pathogens
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