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PLoS Pathogens

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https://www.readbyqxmd.com/read/29352319/activation-of-pi3k-akt-and-erk-during-early-rotavirus-infection-leads-to-v-atpase-dependent-endosomal-acidification-required-for-uncoating
#1
Mahmoud Soliman, Ja-Young Seo, Deok-Song Kim, Ji-Yun Kim, Jun-Gyu Park, Mia Madel Alfajaro, Yeong-Bin Baek, Eun-Hyo Cho, Joseph Kwon, Jong-Soon Choi, Mun-Il Kang, Sang-Ik Park, Kyoung-Oh Cho
The cellular PI3K/Akt and/or MEK/ERK signaling pathways mediate the entry process or endosomal acidification during infection of many viruses. However, their roles in the early infection events of group A rotaviruses (RVAs) have remained elusive. Here, we show that late-penetration (L-P) human DS-1 and bovine NCDV RVA strains stimulate these signaling pathways very early in the infection. Inhibition of both signaling pathways significantly reduced production of viral progeny due to blockage of virus particles in the late endosome, indicating that neither of the two signaling pathways is involved in virus trafficking...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352312/a-role-for-domain-i-of-the-hepatitis-c-virus-ns5a-protein-in-virus-assembly
#2
Chunhong Yin, Niluka Goonawardane, Hazel Stewart, Mark Harris
The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and assembly. NS5A comprises three domains, of these domain I is believed to be involved exclusively in genome replication. In contrast, domains II and III are required for the production of infectious virus particles and are largely dispensable for genome replication. Domain I is highly conserved between HCV and related hepaciviruses, and is highly structured, exhibiting different dimeric conformations. To investigate the functions of domain I in more detail, we conducted a mutagenic study of 12 absolutely conserved and surface-exposed residues within the context of a JFH-1-derived sub-genomic replicon and infectious virus...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352310/leishmania-proteophosphoglycans-regurgitated-from-infected-sand-flies-accelerate-dermal-wound-repair-and-exacerbate-leishmaniasis-via-insulin-like-growth-factor-1-dependent-signalling
#3
Emilie Giraud, Tereza Lěstinová, Tamsyn Derrick, Oihane Martin, Rod J Dillon, Petr Volf, Ingrid Műller, Paul A Bates, Matthew E Rogers
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352299/bunyavirus-requirement-for-endosomal-k-reveals-new-roles-of-cellular-ion-channels-during-infection
#4
Samantha Hover, Becky Foster, Juan Fontana, Alain Kohl, Steve A N Goldstein, John N Barr, Jamel Mankouri
In order to multiply and cause disease a virus must transport its genome from outside the cell into the cytosol, most commonly achieved through the endocytic network. Endosomes transport virus particles to specific cellular destinations and viruses exploit the changing environment of maturing endocytic vesicles as triggers to mediate genome release. Previously we demonstrated that several bunyaviruses, which comprise the largest family of negative sense RNA viruses, require the activity of cellular potassium (K+) channels to cause productive infection...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#5
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352288/phospholipid-scramblase-1-interacts-with-influenza-a-virus-np-impairing-its-nuclear-import-and-thereby-suppressing-virus-replication
#6
Weiyu Luo, Jie Zhang, Libin Liang, Guangwen Wang, Qibing Li, Pengyang Zhu, Yuan Zhou, Junping Li, Yuhui Zhao, Nan Sun, Shanyu Huang, Chenchen Zhou, Yu Chang, Pengfei Cui, Pucheng Chen, Yongping Jiang, Guohua Deng, Zhigao Bu, Chengjun Li, Li Jiang, Hualan Chen
Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352287/ifn%C3%AE-inhibits-g-csf-induced-neutrophil-expansion-and-invasion-of-the-cns-to-prevent-viral-encephalitis
#7
Chandran Ramakrishna, Edouard M Cantin
Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346416/decoding-the-network-of-trypanosoma-brucei-proteins-that-determines-sensitivity-to-apolipoprotein-l1
#8
Rachel B Currier, Anneli Cooper, Hollie Burrell-Saward, Annette MacLeod, Sam Alsford
In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been extensively characterised, our understanding of the range of factors that drive apoL1 action in T. b. brucei is limited...
January 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29338055/a-novel-gerstmann-str%C3%A3-ussler-scheinker-disease-mutation-defines-a-precursor-for-amyloidogenic-8-kda-prp-fragments-and-reveals-n-terminal-structural-changes-shared-by-other-gss-alleles
#9
Robert C C Mercer, Nathalie Daude, Lyudmyla Dorosh, Ze-Lin Fu, Charles E Mays, Hristina Gapeshina, Serene L Wohlgemuth, Claudia Y Acevedo-Morantes, Jing Yang, Neil R Cashman, Michael B Coulthart, Dawn M Pearson, Jeffrey T Joseph, Holger Wille, Jiri G Safar, Gerard H Jansen, Maria Stepanova, Brian D Sykes, David Westaway
To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29338048/ebola-virus-requires-a-host-scramblase-for-externalization-of-phosphatidylserine-on-the-surface-of-viral-particles
#10
Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka
Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29338039/stat3-expression-by-myeloid-cells-is-detrimental-for-the-t-cell-mediated-control-of-infection-with-mycobacterium-tuberculosis
#11
Yu Gao, Juan Ignacio Basile, Cajsa Classon, Dolores Gavier-Widen, Akihiko Yoshimura, Berit Carow, Martin E Rottenberg
STAT3 is a master regulator of the immune responses. Here we show that M. tuberculosis-infected stat3fl/fl lysm cre mice, defective for STAT3 in myeloid cells, contained lower bacterial load in lungs and spleens, reduced granuloma extension but higher levels of pulmonary neutrophils. STAT3-deficient macrophages showed no improved control of intracellular mycobacterial growth. Instead, protection associated to elevated ability of stat3fl/fl lysm cre antigen-presenting cells (APCs) to release IL-6 and IL-23 and to stimulate IL-17 secretion by mycobacteria-specific T cells...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29320578/the-potent-effect-of-mycolactone-on-lipid-membranes
#12
Milène Nitenberg, Anaïs Bénarouche, Ofelia Maniti, Estelle Marion, Laurent Marsollier, Julie Géan, Erick J Dufourc, Jean-François Cavalier, Stéphane Canaan, Agnès P Girard-Egrot
Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated...
January 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29304174/importin-%C3%AE-1-is-required-for-nuclear-import-of-herpes-simplex-virus-proteins-and-capsid-assembly-in-fibroblasts-and-neurons
#13
Katinka Döhner, Ana Ramos-Nascimento, Dagmara Bialy, Fenja Anderson, Ana Hickford-Martinez, Franziska Rother, Thalea Koithan, Kathrin Rudolph, Anna Buch, Ute Prank, Anne Binz, Stefanie Hügel, Robert Jan Lebbink, Rob C Hoeben, Enno Hartmann, Michael Bader, Rudolf Bauerfeind, Beate Sodeik
Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4...
January 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29304169/the-vibrio-cholera-rnd-efflux-systems-impact-virulence-factor-production-and-adaptive-responses-via-periplasmic-sensor-proteins
#14
X Renee Bina, Mondraya F Howard, Dawn L Taylor-Mulneix, Vanessa M Ante, Dillon E Kunkle, James E Bina
Resistance-nodulation-division (RND) efflux systems are ubiquitous transporters in Gram-negative bacteria that are essential for antibiotic resistance. The RND efflux systems also contribute to diverse phenotypes independent of antimicrobial resistance, but the mechanism by which they affect most of these phenotypes is unclear. This is the case in Vibrio cholerae where the RND systems function in antimicrobial resistance and virulence factor production. Herein, we investigated the linkage between RND efflux and V...
January 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29304123/infection-and-depletion-of-cd4-group-1-innate-lymphoid-cells-by-hiv-1-via-type-i-interferon-pathway
#15
Juanjuan Zhao, Liang Cheng, Hongbo Wang, Haisheng Yu, Bo Tu, Qiang Fu, Guangming Li, Qi Wang, Yanling Sun, Xin Zhang, Zhenwen Liu, Weiwei Chen, Liguo Zhang, Lishan Su, Zheng Zhang
Innate lymphoid cells (ILCs) are severely depleted during chronic HIV-1 infection by unclear mechanisms. We report here that human ILC1s comprising of CD4+ and CD4- subpopulations were present in various human lymphoid organs but with different transcription programs and functions. Importantly, CD4+ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. Furthermore, chronic HIV-1 infection activated and depleted both CD4+ and CD4- ILC1s, and impaired their cytokine production activity...
January 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29304101/fab-based-inhibitors-reveal-ubiquitin-independent-functions-for-hiv-vif-neutralization-of-apobec3-restriction-factors
#16
Jennifer M Binning, Amber M Smith, Judd F Hultquist, Charles S Craik, Nathalie Caretta, Melody G Campbell, Lily Burton, Florencia La Greca, Michael J McGregor, Hai M Ta, Koen Bartholomeeusen, B Matija Peterlin, Nevan J Krogan, Natalia Sevillano, Yifan Cheng, John D Gross
The lentiviral protein Viral Infectivity Factor (Vif) counteracts the antiviral effects of host APOBEC3 (A3) proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs) to the Vif complex...
January 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29300789/mycobacterium-tuberculosis-induced-mir-155-subverts-autophagy-by-targeting-atg3-in-human-dendritic-cells
#17
Marilena P Etna, Alessandro Sinigaglia, Angela Grassi, Elena Giacomini, Alessandra Romagnoli, Manuela Pardini, Martina Severa, Melania Cruciani, Fabiana Rizzo, Eleni Ananstasiadou, Barbara Di Camillo, Luisa Barzon, Gian Maria Fimia, Riccardo Manganelli, Eliana M Coccia
Autophagy is a primordial eukaryotic pathway, which provides the immune system with multiple mechanisms for the elimination of invading pathogens including Mycobacterium tuberculosis (Mtb). As a consequence, Mtb has evolved different strategies to hijack the autophagy process. Given the crucial role of human primary dendritic cells (DC) in host immunity control, we characterized Mtb-DC interplay by studying the contribution of cellular microRNAs (miRNAs) in the post-transcriptional regulation of autophagy related genes...
January 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29293695/a-role-for-small-rna-in-regulating-innate-immunity-during-plant-growth
#18
Yingtian Deng, Jubin Wang, Jeffrey Tung, Dan Liu, Yingjia Zhou, Shuang He, Yunlian Du, Barbara Baker, Feng Li
Plant genomes encode large numbers of nucleotide-binding (NB) leucine-rich repeat (LRR) immune receptors (NLR) that mediate effector triggered immunity (ETI) and play key roles in protecting crops from diseases caused by devastating pathogens. Fitness costs are associated with plant NLR genes and regulation of NLR genes by micro(mi)RNAs and phased small interfering RNAs (phasiRNA) is proposed as a mechanism for reducing these fitness costs. However, whether NLR expression and NLR-mediated immunity are regulated during plant growth is unclear...
January 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29293689/tomato-leaf-curl-yunnan-virus-encoded-c4-induces-cell-division-through-enhancing-stability-of-cyclin-d-1-1-via-impairing-nbsk%C3%AE-mediated-phosphorylation-in-nicotiana-benthamiana
#19
Yuzhen Mei, Xiuling Yang, Changjun Huang, Xiuren Zhang, Xueping Zhou
The whitefly-transmitted geminiviruses induce severe developmental abnormalities in plants. Geminivirus-encoded C4 protein functions as one of viral symptom determinants that could induce abnormal cell division. However, the molecular mechanism by which C4 contributes to cell division induction remains unclear. Here we report that tomato leaf curl Yunnan virus (TLCYnV) C4 interacts with a glycogen synthase kinase 3 (GSK3)/SHAGGY-like kinase, designed NbSKη, in Nicotiana benthamiana. Pro32, Asn34 and Thr35 of TLCYnV C4 are critical for its interaction with NbSKη and required for C4-induced typical symptoms...
January 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29293681/indole-3-acetaldehyde-dehydrogenase-dependent-auxin-synthesis-contributes-to-virulence-of-pseudomonas-syringae-strain-dc3000
#20
Sheri A McClerklin, Soon Goo Lee, Christopher P Harper, Ron Nwumeh, Joseph M Jez, Barbara N Kunkel
The bacterial pathogen Pseudomonas syringae modulates plant hormone signaling to promote infection and disease development. P. syringae uses several strategies to manipulate auxin physiology in Arabidopsis thaliana to promote pathogenesis, including its synthesis of indole-3-acetic acid (IAA), the predominant form of auxin in plants, and production of virulence factors that alter auxin responses in the host; however, the role of pathogen-derived auxin in P. syringae pathogenesis is not well understood. Here we demonstrate that P...
January 2, 2018: PLoS Pathogens
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