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PLoS Pathogens

Joseph D Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F Guimaraes, Darren A N Cook, Andrew Steven, Nico Van Rooijen, Judith E Allen, Stephen J Jenkins, Mark J Taylor
Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection...
March 16, 2018: PLoS Pathogens
Natthanon Leelarasamee, Lei Zhang, Cynthia Gleason
Root-knot nematodes secrete effectors that manipulate their host plant cells so that the nematode can successfully establish feeding sites and complete its lifecycle. The root-knot nematode feeding structures, their "giant cells," undergo extensive cytoskeletal remodeling. Previous cytological studies have shown the cytoplasmic actin within the feeding sites looks diffuse. In an effort to study root-knot nematode effectors that are involved in giant cell organogenesis, we have identified a nematode effector called MiPFN3 (Meloidogyne incognita Profilin 3)...
March 15, 2018: PLoS Pathogens
Frances Rocamora, Lei Zhu, Kek Yee Liong, Arjen Dondorp, Olivo Miotto, Sachel Mok, Zbynek Bozdech
Due to their remarkable parasitocidal activity, artemisinins represent the key components of first-line therapies against Plasmodium falciparum malaria. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts to control and ultimately eradicate the disease. To better understand the resistance phenotype, artemisinin-resistant parasite lines were derived from two clones of the 3D7 strain of P. falciparum using a selection regimen that mimics how parasites interact with the drug within patients...
March 14, 2018: PLoS Pathogens
Vandana Sekhar, Teresa Pollicino, Giacomo Diaz, Ronald E Engle, Farah Alayli, Marta Melis, Juraj Kabat, Ashley Tice, Anna Pomerenke, Nihal Altan-Bonnet, Fausto Zamboni, Paolo Lusso, Suzanne U Emerson, Patrizia Farci
Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication...
March 14, 2018: PLoS Pathogens
Brintha Parasumanna Girinathan, Junjun Ou, Bruno Dupuy, Revathi Govind
Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression...
March 12, 2018: PLoS Pathogens
Nicole Stichling, Maarit Suomalainen, Justin W Flatt, Markus Schmid, Martin Pacesa, Silvio Hemmi, Wolfgang Jungraithmayr, Mareike D Maler, Marina A Freudenberg, Andreas Plückthun, Tobias May, Mario Köster, György Fejer, Urs F Greber
Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction...
March 9, 2018: PLoS Pathogens
Kaiyi Zhang, Ambre Riba, Monika Nietschke, Natalia Torow, Urska Repnik, Andreas Pütz, Marcus Fulde, Aline Dupont, Michael Hensel, Mathias Hornef
Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice...
March 9, 2018: PLoS Pathogens
Zhulong Hu, Yuang Wang, Qiaopeng Tang, Xiaodan Yang, Yali Qin, Mingzhou Chen
Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway...
March 8, 2018: PLoS Pathogens
Gah-Hyun Lim, Timothy Hoey, Shifeng Zhu, Marion Clavel, Keshun Yu, Duroy Navarre, Aardra Kachroo, Jean-Marc Deragon, Pradeep Kachroo
The E3 ubiquitin ligase COP1 (Constitutive Photomorphogenesis 1) is a well known component of the light-mediated plant development that acts as a repressor of photomorphogenesis. Here we show that COP1 positively regulates defense against turnip crinkle virus (TCV) and avrRPM1 bacteria by contributing to stability of resistance (R) protein HRT and RPM1, respectively. HRT and RPM1 levels and thereby pathogen resistance is significantly reduced in the cop1 mutant background. Notably, the levels of at least two double-stranded RNA binding (DRB) proteins DRB1 and DRB4 are reduced in the cop1 mutant background suggesting that COP1 affects HRT stability via its effect on the DRB proteins...
March 7, 2018: PLoS Pathogens
Harrison G Jones, Tina Ritschel, Gabriel Pascual, Just P J Brakenhoff, Elissa Keogh, Polina Furmanova-Hollenstein, Ellen Lanckacker, Jehangir S Wadia, Morgan S A Gilman, R Anthony Williamson, Dirk Roymans, Angélique B van 't Wout, Johannes P Langedijk, Jason S McLellan
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models...
March 6, 2018: PLoS Pathogens
Florian Douam, Floriane Fusil, Margot Enguehard, Linda Dib, Francesca Nadalin, Loïc Schwaller, Gabriela Hrebikova, Jimmy Mancip, Laurent Mailly, Roland Montserret, Qiang Ding, Carine Maisse, Emilie Carlot, Ke Xu, Els Verhoeyen, Thomas F Baumert, Alexander Ploss, Alessandra Carbone, François-Loïc Cosset, Dimitri Lavillette
Amino-acid coevolution can be referred to mutational compensatory patterns preserving the function of a protein. Viral envelope glycoproteins, which mediate entry of enveloped viruses into their host cells, are shaped by coevolution signals that confer to viruses the plasticity to evade neutralizing antibodies without altering viral entry mechanisms. The functions and structures of the two envelope glycoproteins of the Hepatitis C Virus (HCV), E1 and E2, are poorly described. Especially, how these two proteins mediate the HCV fusion process between the viral and the cell membrane remains elusive...
March 5, 2018: PLoS Pathogens
Avantika S Chitre, Michael G Kattah, Yenny Y Rosli, Montha Pao, Monika Deswal, Steven G Deeks, Peter W Hunt, Mohamed Abdel-Mohsen, Luis J Montaner, Charles C Kim, Averil Ma, Ma Somsouk, Joseph M McCune Clinical Trial NCT00594880.
March 5, 2018: PLoS Pathogens
Kshitij Wagh, Michael S Seaman, Marshall Zingg, Tomas Fitzsimons, Dan H Barouch, Dennis R Burton, Mark Connors, David D Ho, John R Mascola, Michel C Nussenzweig, Jeffrey Ravetch, Rajeev Gautam, Malcolm A Martin, David C Montefiori, Bette Korber NCT02960581.
March 5, 2018: PLoS Pathogens
Kendra A Bussey, Ulrike Lau, Sophie Schumann, Antonio Gallo, Lisa Osbelt, Markus Stempel, Christine Arnold, Josef Wissing, Hans Henrik Gad, Rune Hartmann, Wolfram Brune, Lothar Jänsch, Adrian Whitehouse, Melanie M Brinkmann
Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the few oncogenic human viruses known to date. Its large genome encodes more than 85 proteins and includes both unique viral proteins as well as proteins conserved amongst herpesviruses. KSHV ORF20 is a member of the herpesviral core UL24 family, but the function of ORF20 and its role in the viral life cycle is not well understood. ORF20 encodes three largely uncharacterized isoforms, which we found were localized predominantly in the nuclei and nucleoli...
March 2, 2018: PLoS Pathogens
Bo G Lindberg, Xiongzhuo Tang, Widad Dantoft, Priya Gohel, Shiva Seyedoleslami Esfahani, Jessica M Lindvall, Ylva Engström
Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub) encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila...
March 2, 2018: PLoS Pathogens
Charles-Adrien Richard, Vincent Rincheval, Safa Lassoued, Jenna Fix, Christophe Cardone, Camille Esneau, Sergei Nekhai, Marie Galloux, Marie-Anne Rameix-Welti, Christina Sizun, Jean-François Eléouët
Respiratory syncytial virus (RSV) RNA synthesis occurs in cytoplasmic inclusion bodies (IBs) in which all the components of the viral RNA polymerase are concentrated. In this work, we show that RSV P protein recruits the essential RSV transcription factor M2-1 to IBs independently of the phosphorylation state of M2-1. We also show that M2-1 dephosphorylation is achieved by a complex formed between P and the cellular phosphatase PP1. We identified the PP1 binding site of P, which is an RVxF-like motif located nearby and upstream of the M2-1 binding region...
February 28, 2018: PLoS Pathogens
Kimberley F Prior, Daan R van der Veen, Aidan J O'Donnell, Katherine Cumnock, David Schneider, Arnab Pain, Amit Subudhi, Abhinay Ramaprasad, Samuel S C Rund, Nicholas J Savill, Sarah E Reece
Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment. Recent work shows that daily (circadian) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hosts. Because parasite rhythms matter for their fitness, understanding how they are regulated could lead to innovative ways to reduce the severity and spread of diseases. Here, we examine how host circadian rhythms influence rhythms in the asexual replication of malaria parasites...
February 26, 2018: PLoS Pathogens
Paul A Beare, Brendan M Jeffrey, Carrie M Long, Craig M Martens, Robert A Heinzen
Coxiella burnetii is an intracellular pathogen that causes human Q fever, a disease that normally presents as a severe flu-like illness. Due to high infectivity and disease severity, the pathogen is considered a risk group 3 organism. Full-length lipopolysaccharide (LPS) is required for full virulence and disease by C. burnetii and is the only virulence factor currently defined by infection of an immunocompetent animal. Transition of virulent phase I bacteria with smooth LPS, to avirulent phase II bacteria with rough LPS, occurs during in vitro passage...
February 26, 2018: PLoS Pathogens
Emily N Gallichotte, Thomas J Baric, Boyd L Yount, Douglas G Widman, Anna Durbin, Steve Whitehead, Ralph S Baric, Aravinda M de Silva
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome. It is estimated that a third of the world's population is at risk for infection, with an estimated 390 million infections annually. Dengue virus serotype 2 (DENV2) causes severe epidemics, and the leading tetravalent dengue vaccine has lower efficacy against DENV2 compared to the other 3 serotypes. In natural DENV2 infections, strongly neutralizing type-specific antibodies provide protection against subsequent DENV2 infection...
February 26, 2018: PLoS Pathogens
Yan Huo, Yuanling Yu, Liying Chen, Qiong Li, Mengting Zhang, Zhiyu Song, Xiaoying Chen, Rongxiang Fang, Lili Zhang
Insect vitellogenin (Vg) has been considered to be synthesized in the fat body. Here, we found that abundant Vg protein is synthesized in Laodelphax striatellus hemocytes as well. We also determined that only the hemocyte-produced Vg binds to Rice stripe virus (RSV) in vivo. Examination of the subunit composition of L. striatellus Vg (LsVg) revealed that LsVg was processed differently after its expression in different tissues. The LsVg subunit able to bind to RSV exist stably only in hemocytes, while fat body-produced LsVg lacks the RSV-interacting subunit...
February 23, 2018: PLoS Pathogens
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