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PLoS Pathogens

Duncan Wilson, Julian R Naglik, Bernhard Hube
No abstract text is available yet for this article.
October 2016: PLoS Pathogens
Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I Bukrinsky, Paul J Brindley
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein...
October 2016: PLoS Pathogens
Fumika Mi-Ichi, Hiroki Yoshida, Shinjiro Hamano
Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by "encystation" and "excystation." Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent...
October 2016: PLoS Pathogens
Qian Qi, Mary M Cavanagh, Sabine Le Saux, Lisa E Wagar, Sally Mackey, Jinyu Hu, Holden Maecker, Gary E Swan, Mark M Davis, Cornelia L Dekker, Lu Tian, Cornelia M Weyand, Jörg J Goronzy
Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age...
October 2016: PLoS Pathogens
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
Xianxiu Wan, Jian-Jun Wen, Sue-Jie Koo, Lisa Yi Liang, Nisha Jain Garg
Chronic chagasic cardiomyopathy (CCM) is presented by increased oxidative/inflammatory stress and decreased mitochondrial bioenergetics. SIRT1 senses the redox changes and integrates mitochondrial metabolism and inflammation; and SIRT1 deficiency may be a major determinant in CCM. To test this, C57BL/6 mice were infected with Trypanosoma cruzi (Tc), treated with SIRT1 agonists (resveratrol or SRT1720), and monitored during chronic phase (~150 days post-infection). Resveratrol treatment was partially beneficial in controlling the pathologic processes in Chagas disease...
October 2016: PLoS Pathogens
Ke Ren, Wei Zhang, Xiaoqing Chen, Yingyu Ma, Yue Dai, Yimei Fan, Yayi Hou, Ren Xiang Tan, Erguang Li
The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4) as a critical player in HSV infection. We show that treatment with pan BD domain inhibitor enhanced both HSV infection. Using JQ1 as a probe, we found that JQ1, a defined BD1 inhibitor, acts through BRD4 protein since knockdown of BRD4 expression ablated JQ1 effect on HSV infection...
October 2016: PLoS Pathogens
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
Haley Echlin, Matthew W Frank, Amy Iverson, Ti-Cheng Chang, Michael D L Johnson, Charles O Rock, Jason W Rosch
The pneumococcus is one of the most prodigious producers of hydrogen peroxide amongst bacterial pathogens. Hydrogen peroxide production by the pneumococcus has been implicated in antibiotic synergism, competition between other bacterial colonizers of the nasopharynx, and damage to epithelial cells. However, the role during invasive disease has been less clear with mutants defective in hydrogen peroxide production demonstrating both attenuation and heightened invasive disease capacity depending upon strain and serotype background...
October 2016: PLoS Pathogens
Shasha Li, Hao Hu, Zhiheng He, Deguang Liang, Rui Sun, Ke Lan
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation...
October 2016: PLoS Pathogens
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
Kimberly F Starr, Eric A Porsch, Patrick C Seed, Christian Heiss, Radnaa Naran, L Scott Forsberg, Uri Amit, Pablo Yagupsky, Parastoo Azadi, Joseph W St Geme
Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269-492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases...
October 2016: PLoS Pathogens
Robert N Kirchdoerfer, Crystal L Moyer, Dafna M Abelson, Erica Ollmann Saphire
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays...
October 2016: PLoS Pathogens
Jovan Nikolic, Ahmet Civas, Zoé Lama, Cécile Lagaudrière-Gesbert, Danielle Blondel
Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection...
October 2016: PLoS Pathogens
Michele Chu, Michael J G Mallozzi, Bryan P Roxas, Lisa Bertolo, Mario A Monteiro, Al Agellon, V K Viswanathan, Gayatri Vedantam
Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis. Cell wall glycopolymers (CWGs) influence the virulence of various pathogens. Five C. difficile CWGs, including PSII, have been structurally characterized, but their biosynthesis and significance in C. difficile infection is unknown. We explored the contribution of a conserved CWG locus to C...
October 2016: PLoS Pathogens
Aline Koch, Dagmar Biedenkopf, Alexandra Furch, Lennart Weber, Oliver Rossbach, Eltayb Abdellatef, Lukas Linicus, Jan Johannsmeier, Lukas Jelonek, Alexander Goesmann, Vinitha Cardoza, John McMillan, Tobias Mentzel, Karl-Heinz Kogel
Meeting the increasing food and energy demands of a growing population will require the development of ground-breaking strategies that promote sustainable plant production. Host-induced gene silencing has shown great potential for controlling pest and diseases in crop plants. However, while delivery of inhibitory noncoding double-stranded (ds)RNA by transgenic expression is a promising concept, it requires the generation of transgenic crop plants which may cause substantial delay for application strategies depending on the transformability and genetic stability of the crop plant species...
October 2016: PLoS Pathogens
Naomi H Philip, Alexandra DeLaney, Lance W Peterson, Melanie Santos-Marrero, Jennifer T Grier, Yan Sun, Meghan A Wynosky-Dolfi, Erin E Zwack, Baofeng Hu, Tayla M Olsen, Anthony Rongvaux, Scott D Pope, Carolina B López, Andrew Oberst, Daniel P Beiting, Jorge Henao-Mejia, Igor E Brodsky
Caspases regulate cell death programs in response to environmental stresses, including infection and inflammation, and are therefore critical for the proper operation of the mammalian immune system. Caspase-8 is necessary for optimal production of inflammatory cytokines and host defense against infection by multiple pathogens including Yersinia, but whether this is due to death of infected cells or an intrinsic role of caspase-8 in TLR-induced gene expression is unknown. Caspase-8 activation at death signaling complexes results in its autoprocessing and subsequent cleavage and activation of its downstream apoptotic targets...
October 2016: PLoS Pathogens
Susanna K P Lau, Patrick C Y Woo, Kenneth S M Li, Hao-Ji Zhang, Rachel Y Y Fan, Anna J X Zhang, Brandon C C Chan, Carol S F Lam, Cyril C Y Yip, Ming-Chi Yuen, Kwok-Hung Chan, Zhi-Wei Chen, Kwok-Yung Yuen
While novel picornaviruses are being discovered in rodents, their host range and pathogenicity are largely unknown. We identified two novel picornaviruses, rosavirus B from the street rat, Norway rat, and rosavirus C from five different wild rat species (chestnut spiny rat, greater bandicoot rat, Indochinese forest rat, roof rat and Coxing's white-bellied rat) in China. Analysis of 13 complete genome sequences showed that "Rosavirus B" and "Rosavirus C" represent two potentially novel picornavirus species infecting different rodents...
October 2016: PLoS Pathogens
Emilio Yángüez, Alicia García-Culebras, Aldo Frau, Catalina Llompart, Klaus-Peter Knobeloch, Sylvia Gutierrez-Erlandsson, Adolfo García-Sastre, Mariano Esteban, Amelia Nieto, Susana Guerra
[This corrects the article DOI: 10.1371/journal.ppat.1003632.].
October 2016: PLoS Pathogens
Suomeng Dong, Yuanchao Wang
[This corrects the article DOI: 10.1371/journal.ppat.1005704.].
October 2016: PLoS Pathogens
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