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PLoS Pathogens

Xuehong Jia, Bo Liu, Linlin Bao, Qi Lv, Fengdi Li, Hui Li, Yunqing An, Xulong Zhang, Bin Cao, Chen Wang
Severe influenza A virus infection causes high mortality and morbidity worldwide due to delayed antiviral treatment and inducing overwhelming immune responses, which contribute to immunopathological lung injury. Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), was effective in improving clinical outcomes in patients with severe H1N1 infection; however, the mechanisms by which it attenuates acute lung injury have not been elucidated. Here, delayed oseltamivir treatment was used to mimic clinical settings on lethal influenza A (H1N1) pdm09 virus (pH1N1) infection mice model...
November 13, 2018: PLoS Pathogens
Yolande Grobler, Chi Y Yun, David J Kahler, Casey M Bergman, Hangnoh Lee, Brian Oliver, Ruth Lehmann
Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts. Insects such as mosquitos act as vectors for many devastating human viruses such as Dengue, West Nile, and Zika. Remarkably, Wolbachia infection provides insect hosts with resistance to many arboviruses thereby rendering the insects ineffective as vectors. To utilize Wolbachia effectively as a tool against vector-borne viruses a better understanding of the host-Wolbachia relationship is needed. To investigate Wolbachia-insect interactions we used the Wolbachia/Drosophila model that provides a genetically tractable system for studying host-pathogen interactions...
November 13, 2018: PLoS Pathogens
Justine Schaeffer, Xavier Carnec, Stéphanie Reynard, Mathieu Mateo, Caroline Picard, Natalia Pietrosemoli, Marie-Agnès Dilliès, Sylvain Baize
Lassa virus (LASV) is responsible for a viral hemorrhagic fever in humans and the death of 3,000 to 5,000 people every year. The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid dendritic cells (mDC) to LASV, as mDCs are involved in both IFN-I production and T-cell activation. We compared the response of primary human mDCs to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic...
November 12, 2018: PLoS Pathogens
Artemis Perraki, Julien Gronnier, Paul Gouguet, Marie Boudsocq, Anne-Flore Deroubaix, Vincent Simon, Sylvie German-Retana, Cyril Zipfel, Emmanuelle Bayer, Sébastien Mongrand, Véronique Germain, Anthony Legrand, Birgit Habenstein
Plants respond to pathogens through dynamic regulation of plasma membrane-bound signaling pathways. To date, how the plant plasma membrane is involved in responses to viruses is mostly unknown. Here, we show that plant cells sense the Potato virus X (PVX) COAT PROTEIN and TRIPLE GENE BLOCK 1 proteins and subsequently trigger the activation of a membrane-bound calcium-dependent kinase. We show that the Arabidopsis thaliana CALCIUM-DEPENDENT PROTEIN KINASE 3-interacts with group 1 REMORINs in vivo, phosphorylates the intrinsically disordered N-terminal domain of the Group 1 REMORIN REM1...
November 12, 2018: PLoS Pathogens
Angela D Pack, Matthew H Collins, Charles S Rosenberg, Rick L Tarleton
Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction described for other persistent infections. In this study, we have evaluated the role of CD8+ T cells during chronic T. cruzi infection (>100 dpi), with a focus on sites of pathogen persistence. Consistent with repetitive antigen exposure during chronic infection, parasite-specific CD8+ T cells from multiple organs expressed high levels of KLRG1, but exhibit a preferential accumulation of CD69+ cells in skeletal muscle, indicating recent antigen encounter in a niche for T...
November 12, 2018: PLoS Pathogens
Natacha Merindol, Mohamed El-Far, Mohamed Sylla, Nasser Masroori, Caroline Dufour, Jia-Xin Li, Pearl Cherry, Mélodie B Plourde, Cécile Tremblay, Lionel Berthoux
Elite controllers (ECs) are a rare subset of HIV-1 slow progressors characterized by prolonged viremia suppression. HLA alleles B27 and B57 promote the cytotoxic T lymphocyte (CTL)-mediated depletion of infected cells in ECs, leading to the emergence of escape mutations in the viral capsid (CA). Whether those mutations modulate CA detection by innate sensors and effectors is poorly known. Here, we investigated the targeting of CA from B27/B57+ individuals by cytosolic antiviral factors Mx2 and TRIM5α. Toward that aim, we constructed chimeric HIV-1 vectors using CA isolated from B27/B57+ or control subjects...
November 12, 2018: PLoS Pathogens
Yong-Yao Yu, Weiguang Kong, Ya-Xing Yin, Fen Dong, Zhen-Yu Huang, Guang-Mei Yin, Shuai Dong, Irene Salinas, Yong-An Zhang, Zhen Xu
The olfactory organ of vertebrates receives chemical cues present in the air or water and, at the same time, they are exposed to invading pathogens. Nasal-associated lymphoid tissue (NALT), which serves as a mucosal inductive site for humoral immune responses against antigen stimulation in mammals, is present also in teleosts. IgT in teleosts is responsible for similar functions to those carried out by IgA in mammals. Moreover, teleost NALT is known to contain B-cells and teleost nasal mucus contains immunoglobulins (Igs)...
November 5, 2018: PLoS Pathogens
Marie Leoz, Petra Kukanja, Zeping Luo, Fang Huang, Daniele C Cary, B Matija Peterlin, Koh Fujinaga
Transcription of HIV provirus is a key step of the viral cycle, and depends on the recruitment of the cellular positive transcription elongation factor (P-TEFb) to the HIV promoter. The viral transactivator Tat can displace P-TEFb from the 7SK small nuclear ribonucleoprotein, where it is bound and inactivated by HEXIM1, and bring it to TAR, which allows the stalled RNA polymerase II to transition to successful transcription elongation. In this study, we designed a chimeric inhibitor of HIV transcription by combining functional domains from HEXIM1 and Tat...
November 5, 2018: PLoS Pathogens
Michael Hulse, Lisa B Caruso, Jozef Madzo, Yinfei Tan, Sarah Johnson, Italo Tempera
Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Poly(ADP-ribose) polymerase 1 (PARP1) regulates accessibility of chromatin, alters functions of transcriptional activators and repressors, and has been directly implicated in transcriptional activation. Previously we showed that LMP1 activates PARP1 and increases Poly(ADP-ribos)ylation (PARylation) through PARP1. Therefore, to identify targets of LMP1 that are regulated through PARP1, LMP1 was ectopically expressed in an EBV-negative Burkitt's lymphoma cell line...
November 5, 2018: PLoS Pathogens
Celia C LaBranche, Andrew T McGuire, Matthew D Gray, Shay Behrens, Tongqing Zhou, Quentin J Sattentau, James Peacock, Amanda Eaton, Kelli Greene, Hongmei Gao, Haili Tang, Lautaro G Perez, Kevin O Saunders, John R Mascola, Barton F Haynes, Leonidas Stamatatos, David C Montefiori
Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination. VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models. Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages...
November 5, 2018: PLoS Pathogens
Yiyang Jiang, Hailong Yu, Fudong Li, Lin Cheng, Lingru Zhu, Yunyu Shi, Qingguo Gong
Methyltransferase RlmCD was previously shown to be responsible for the introduction of C5 methylation at both U747 and U1939 of the 23S ribosomal RNA in Streptococcus pneumoniae. Intriguingly, its structural homologue, RumA, can only catalyze the methylation of U1939, while RlmC is the dedicated enzyme for m5U747 in Escherichia coli. In this study, we describe the structure of RlmCD in complex with its cofactor and the RNA substrate containing U747 at 2.00 Å or U1939 at 3.10 Å. We demonstrate that multiple structural features collaborate to establish the dual enzymatic activities of RlmCD...
November 2, 2018: PLoS Pathogens
Lele Zhang, Ning Wei, Ye Cui, Ze Hong, Xing Liu, Qiang Wang, Senlin Li, Heng Liu, Huansha Yu, Yanni Cai, Quanyi Wang, Juanjuan Zhu, Wei Meng, Zhengjun Chen, Chen Wang
Stimulator of interferon genes (STING) is critical for cytosolic DNA-triggered innate immunity. STING is modified by several types of polyubiquitin chains. Here, we report that the deubiquitinase CYLD sustains STING signaling by stabilizing the STING protein. CYLD deficiency promoted the K48-linked polyubiquitination and degradation of STING, attenuating the induction of IRF3-responsive genes after HSV-1 infection or the transfection of DNA ligands. Additionally, CYLD knockout mice were more susceptible to HSV-1 infection than their wild-type (WT) littermates...
November 2, 2018: PLoS Pathogens
Erika Pineda, Magali Thonnus, Muriel Mazet, Arnaud Mourier, Edern Cahoreau, Hanna Kulyk, Jean-William Dupuy, Marc Biran, Cyril Masante, Stefan Allmann, Loïc Rivière, Brice Rotureau, Jean-Charles Portais, Frédéric Bringaud
The bloodstream forms of Trypanosoma brucei (BSF), the parasite protist causing sleeping sickness, primarily proliferate in the blood of their mammalian hosts. The skin and adipose tissues were recently identified as additional major sites for parasite development. Glucose was the only carbon source known to be used by bloodstream trypanosomes to feed their central carbon metabolism, however, the metabolic behaviour of extravascular tissue-adapted parasites has not been addressed yet. Since the production of glycerol is an important primary function of adipocytes, we have adapted BSF trypanosomes to a glucose-depleted but glycerol-rich culture medium (CMM_Glyc/GlcNAc) and compared their metabolism and proteome to those of parasites grown in standard glucose-rich conditions (CMM_Glc)...
November 1, 2018: PLoS Pathogens
Micaela Elvira Martinez
No abstract text is available yet for this article.
November 2018: PLoS Pathogens
Zigui Chen, Rob DeSalle, Mark Schiffman, Rolando Herrero, Charles E Wood, Julio C Ruiz, Gary M Clifford, Paul K S Chan, Robert D Burk
Recent discoveries on the origins of modern humans from multiple archaic hominin populations and the diversity of human papillomaviruses (HPVs) suggest a complex scenario of virus-host evolution. To evaluate the origin of HPV pathogenesis, we estimated the phylogeny, timing, and dispersal of HPV16 variants using a Bayesian Markov Chain Monte Carlo framework. To increase precision, we identified and characterized non-human primate papillomaviruses from New and Old World monkeys to set molecular clock models...
November 2018: PLoS Pathogens
Philip Goulder, Steven G Deeks
In this brief review and perspective, we address the question of whether the immune responses that bring about immune control of acute HIV infection are the same as, or distinct from, those that maintain long-term viral suppression once control of viremia has been achieved. To this end, we describe the natural history of elite and post-treatment control, noting the lack of data regarding what happens acutely. We review the evidence suggesting that the two clinical phenotypes may differ in terms of the mechanisms required to achieve and maintain control, as well as the level of inflammation that persists once a steady state is achieved...
November 2018: PLoS Pathogens
Johanna B Withers, Eric S Li, Tenaya K Vallery, Therese A Yario, Joan A Steitz
During lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear viral long noncoding RNA known as PAN RNA becomes the most abundant polyadenylated transcript in the cell. Knockout or knockdown of KSHV PAN RNA results in loss of late lytic viral gene expression and, consequently, reduction of progeny virion release from the cell. Here, we demonstrate that knockdown of PAN RNA from the related Rhesus macaque rhadinovirus (RRV) phenocopies that of KSHV PAN RNA. These two PAN RNA homologs, although lacking significant nucleotide sequence conservation, can functionally substitute for each other to rescue phenotypes associated with the absence of PAN RNA expression...
November 2018: PLoS Pathogens
Amir Saberi, Anastasia A Gulyaeva, John L Brubacher, Phillip A Newmark, Alexander E Gorbalenya
RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive host environment). A 33.5 kilobase (kb) nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is in the 100-300 kb range. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps towards DNA-based life, studies of larger RNA viruses advance our understanding of the size constraints on RNP entities and the role of genome size in virus adaptation...
November 2018: PLoS Pathogens
Sharie Keanne C Ganchua, Anthony M Cadena, Pauline Maiello, Hannah P Gideon, Amy J Myers, Beth F Junecko, Edwin C Klein, Philana Ling Lin, Joshua T Mattila, JoAnne L Flynn
Tuberculosis is commonly considered a chronic lung disease, however, extrapulmonary infection can occur in any organ. Even though lymph nodes (LN) are among the most common sites of extrapulmonary Mycobacterium tuberculosis (Mtb) infection, and thoracic LNs are frequently infected in humans, bacterial dynamics and the effect of Mtb infection in LN structure and function is relatively unstudied. We surveyed thoracic LNs from Mtb-infected cynomolgus and rhesus macaques analyzing PET CT scans, bacterial burden, LN structure and immune function...
November 2018: PLoS Pathogens
Kirsten Kuipers, Kristen L Lokken, Tonia Zangari, Mark A Boyer, Sunny Shin, Jeffrey N Weiser
Young age is a risk factor for prolonged colonization by common pathogens residing in their upper respiratory tract (URT). Why children present with more persistent colonization is unknown and there is relatively little insight into the host-pathogen interactions that contribute to persistent colonization. To identify factors permissive for persistent colonization during infancy, we utilized an infant mouse model of Streptococcus pneumoniae colonization in which clearance from the mucosal surface of the URT requires many weeks to months...
October 2018: PLoS Pathogens
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