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https://www.readbyqxmd.com/read/28542576/ebola-virus-glycoprotein-directly-triggers-t-lymphocyte-death-despite-of-the-lack-of-infection
#1
Mathieu Iampietro, Patrick Younan, Andrew Nishida, Mukta Dutta, Ndongala Michel Lubaki, Rodrigo I Santos, Richard A Koup, Michael G Katze, Alexander Bukreyev
Fatal outcomes of Ebola virus (EBOV) infections are typically preceded by a 'sepsis-like' syndrome and lymphopenia despite T cells being resistant to Ebola infection. The mechanisms that lead to T lymphocytes death remain largely unknown; however, the degree of lymphopenia is highly correlative with fatalities. Here we investigated whether the addition of EBOV or its envelope glycoprotein (GP) to isolated primary human CD4+ T cells induced cell death. We observed a significant decrease in cell viability in a GP-dependent manner, which is suggestive of a direct role of GP in T cell death...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28539447/a-map-of-the-arenavirus-nucleoprotein-host-protein-interactome-reveals-that-jun%C3%A3-n-virus-selectively-impairs-the-antiviral-activity-of-pkr
#2
Benjamin R King, Dylan Hershkowitz, Philip L Eisenhauer, Marion E Weir, Christopher M Ziegler, Joanne Russo, Emily A Bruce, Bryan A Ballif, Jason Botten
Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. Encoding only four proteins to accomplish the viral life cycle, each arenavirus protein likely plays unappreciated accessory roles during infection. Here, we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoprotein (NP) of the Old World arenavirus lymphocytic choriomeningitis (LCMV) and the New World arenavirus Junín Candid #1 (JUNV). Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514687/particulate-array-of-well-ordered-hiv-clade-c-env-trimers-elicits-neutralizing-antibodies-that-display-a-unique-v2-cap-approach
#3
Paola Martinez-Murillo, Karen Tran, Javier Guenaga, Gustaf Lindgren, Monika Àdori, Yu Feng, Ganesh E Phad, Néstor Vázquez Bernat, Shridhar Bale, Jidnyasa Ingale, Viktoriya Dubrovskaya, Sijy O'Dell, Lotta Pramanik, Mats Spångberg, Martin Corcoran, Karin Loré, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam
The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28493891/antibody-to-hsv-gd-peptide-induced-by-vaccination-does-not-protect-against-hsv-2-infection-in-hsv-2-seronegative-women
#4
Peter B Gilbert, Jean-Louis Excler, Georgia D Tomaras, Lindsay N Carpp, Barton F Haynes, Hua-Xin Liao, David C Montefiori, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Gustavo H Kijak, Sodsai Tovanabutra, Donald P Francis, Carter Lee, Faruk Sinangil, Phillip W Berman, Nakorn Premsri, Prayura Kunasol, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Rhoda Morrow, Lawrence Corey, Jerome H Kim
BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28490595/sensing-of-hiv-1-entry-triggers-a-type-i-interferon-response-in-human-primary-macrophages
#5
Jérémie Decalf, Marion Desdouits, Vasco Rodrigues, François-Xavier Gobert, Matteo Gentili, Santy Marques-Ladeira, Célia Chamontin, Marylène Mougel, Bruna Cunha de Alencar, Philippe Benaroch
Along with CD4+ T lymphocytes, macrophages are a major cellular source of HIV-1 replication, and a potential viral reservoir. Following entry and reverse transcription in macrophages, cloaking of the viral cDNA by the HIV-1 capsid limits its cytosolic detection, enabling efficient replication. However, whether incoming HIV-1 particles are sensed by macrophages prior to reverse-transcription, remains unclear. Here, we show that HIV-1 triggers a broad expression of interferon-stimulated genes (ISG) in monocyte-derived macrophages within a few hours after infection...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28479588/clinical-impact-of-the-early-alanine-amininotransferase-flare-during-tenofovir-monotherapy-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b
#6
Hee Yeon Seo, Han Ah Lee, Soon Young Ko, Joon Ho Wang, Jeong Han Kim, Won Hyeok Choe, So Young Kwon
Background/Aims: Little is known about the effect of early flares on response during first-line tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB). The aim of this study was to investigate the incidence and outcome of early alanine aminotransferase (ALT) flare in treatment-naive patients with CHB during long-term TDF monotherapy. Methods: One hundred eighty-one treatment-naive CHB patients were treated with a 300-mg once-daily dose of TDF for more than 12 weeks...
May 8, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28456632/tumor-necrosis-factor-inhibits-spread-of-hepatitis-c-virus-among-liver-cells-independent-from-interferons
#7
Stephen M Laidlaw, Svetlana Marukian, Rachel H Gilmore, Siobhán B Cashman, Volodymyr Nechyporuk-Zloy, Charles M Rice, Lynn B Dustin
BACKGROUND & AIMS: Tumor necrosis factor (TNF) an inflammatory cytokine expressed by human fetal liver cells (HFLCs) following infection with cell culture-derived hepatitis C virus. TNF has been reported to increase entry of HCV pseudoparticles into hepatoma cells and inhibit signaling by interferon alpha (IFNA), but have no effect on replication of HCV RNA. We investigated the effects of TNF on HCV infection of and spread among Huh-7 hepatoma cells and primary HFLCs.  METHODS: Human hepatoma (Huh-7 and Huh-7...
April 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28450453/microtubule-dynamics-drive-enhanced-chromatin-motion-and-mobilize-telomeres-in-response-to-dna-damage
#8
Josh Lawrimore, Timothy M Barry, Raymond M Barry, Alyssa C York, Diana M Cook, Kristen Akialis, Jolien Tyler, Paula Vasquez, Elaine Yeh, Kerry Bloom
Chromatin exhibits increased mobility upon DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage-induced chromosome mobility, we employ single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands following exposure to DNA damaging agents. The magnitude of chromatin mobility induced by a single double strand break requires active microtubule function...
April 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#9
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28430890/acceptability-comparison-between-hawley-retainers-and-vacuum-formed-retainers-in-orthodontic-adult-patients-a-single-centre-randomized-controlled-trial
#10
Mohammed Saleh, Mohammad Y Hajeer, Dieter Muessig
Background: Hawley retainers (HRs) and vacuum formed retainers (VFRs) are the most commonly used removable retainers in the orthodontic practice. Patients' cooperation in wearing these appliances is affected by the levels of discomfort and oral impairment. The evidence regarding their acceptably among orthodontic patients is limited. Aims: To compare the acceptability of HRs and VFRs over a 6-month period in a group of fixed orthodontic patients. Trial Design: Two-arm parallel-group randomized controlled trial...
April 19, 2017: European Journal of Orthodontics
https://www.readbyqxmd.com/read/28373273/appropriate-regulation-of-the-%C3%AF-e-dependent-envelope-stress-response-is-necessary-to-maintain-cell-envelope-integrity-and-stationary-phase-survival-in-escherichia-coli
#11
Hervé Nicoloff, Saumya Gopalkrishnan, Sarah E Ades
The alternative sigma factor σ(E) is a key component of the Escherichia coli response to cell envelope stress and is required for viability even in the absence of stress. σ(E) activity increases during entry into stationary phase suggesting an important role for σ(E) when nutrients are limiting. Elevated σ(E) activity has been proposed to activate a pathway leading to lysis of non-culturable cells that accumulate during early stationary phase. To better understand σ(E)-directed cell lysis and the role of σ(E) in stationary phase, we investigated the effects of elevated σ(E) activity in cultures grown for ten days...
April 3, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28366604/single-n277a-substitution-in-c2-of-simian-immunodeficiency-virus-envelope-influences-vaccine-elicited-cd4i-neutralizing-and-anti-v2-antibody-responses
#12
Xian Tang, Jia Guo, Lin Cheng, Caijun Sun, Li Liu, Teng Zuo, Hui Wang, Ling Chen, Linqi Zhang, Zhiwei Chen
An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28365225/safety-and-immunogenicity-of-one-versus-two-doses-of-takeda-s-tetravalent-dengue-vaccine-in-children-in-asia-and-latin-america-interim-results-from-a-phase-2-randomised-placebo-controlled-study
#13
Xavier Sáez-Llorens, Vianney Tricou, Delia Yu, Luis Rivera, Suely Tuboi, Pedro Garbes, Astrid Borkowski, Derek Wallace
BACKGROUND: Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4)...
March 29, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28362674/human-frequency-following-responses-to-vocoded-speech
#14
Saradha Ananthakrishnan, Xin Luo, Ananthanarayan Krishnan
OBJECTIVES: Vocoders offer an effective platform to simulate the effects of cochlear implant speech processing strategies in normal-hearing listeners. Several behavioral studies have examined the effects of varying spectral and temporal cues on vocoded speech perception; however, little is known about the neural indices of vocoded speech perception. Here, the scalp-recorded frequency following response (FFR) was used to study the effects of varying spectral and temporal cues on brainstem neural representation of specific acoustic cues, the temporal envelope periodicity related to fundamental frequency (F0) and temporal fine structure (TFS) related to formant and formant-related frequencies, as reflected in the phase-locked neural activity in response to vocoded speech...
March 30, 2017: Ear and Hearing
https://www.readbyqxmd.com/read/28298291/plasmablast-response-to-primary-rhesus-cytomegalovirus-cmv-infection-in-a-monkey-model-of-congenital-cmv-transmission
#15
Qihua Fan, Cody S Nelson, Kristy M Bialas, Flavia Chiuppesi, Joshua Amos, Thaddeus C Gurley, Dawn Jones Marshall, Joshua Eudailey, Holly Heimsath, Jonathon Himes, Ashlesha Deshpande, Mark R Walter, Felix Wussow, Don J Diamond, Peter A Barry, M Anthony Moody, Amitinder Kaur, Sallie R Permar
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4(+) T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant...
May 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28284242/epstein-barr-virus-nuclear-antigen-1-interacts-with-regulator-of-chromosome-condensation-1-dynamically-throughout-the-cell-cycle
#16
Thibaut Deschamps, Quentin Bazot, Derek M Leske, Ruth MacLeod, Dimitri Mompelat, Lionel Tafforeau, Vincent Lotteau, Vincent Maréchal, George S Baillie, Henri Gruffat, Joanna B Wilson, Evelyne Manet
The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is a sequence-specific DNA-binding protein that plays an essential role in viral episome replication and segregation, by recruiting the cellular complex of DNA replication onto the origin (oriP) and by tethering the viral DNA onto the mitotic chromosomes. Whereas the mechanisms of viral DNA replication are well documented, those involved in tethering EBNA1 to the cellular chromatin are far from being understood. Here, we have identified regulator of chromosome condensation 1 (RCC1) as a novel cellular partner for EBNA1...
February 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28283525/molecular-viability-testing-of-uv-inactivated-bacteria
#17
Kris M Weigel, Felicia K Nguyen, Moira R Kearney, John S Meschke, Gerard A Cangelosi
PCR is effective in detecting bacterial DNA in samples, but it is unable to differentiate viable bacteria from inactivated cells or free DNA fragments. New PCR-based analytical strategies have been developed to address this limitation. Molecular viability testing (MVT) correlates bacterial viability with the ability to rapidly synthesize species-specific rRNA precursors (pre-rRNA) in response to brief nutritional stimulation. Previous studies demonstrated that MVT can assess bacterial inactivation by chlorine, serum, and low-temperature pasteurization...
May 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28281035/acoustic-context-alters-vowel-categorization-in-perception-of-noise-vocoded-speech
#18
Christian E Stilp
Normal-hearing listeners' speech perception is widely influenced by spectral contrast effects (SCEs), where perception of a given sound is biased away from stable spectral properties of preceding sounds. Despite this influence, it is not clear how these contrast effects affect speech perception for cochlear implant (CI) users whose spectral resolution is notoriously poor. This knowledge is important for understanding how CIs might better encode key spectral properties of the listening environment. Here, SCEs were measured in normal-hearing listeners using noise-vocoded speech to simulate poor spectral resolution...
June 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28276012/isolation-of-contact-sites-between-inner-and-outer-mitochondrial-membranes
#19
Max Harner
Mitochondria are essential organelles of all eukaryotic cells. They perform a plethora of important metabolic functions and have a highly complex architecture that differs drastically between different cells and tissues. Mitochondria are delimited from the cytosol by the mitochondrial envelope that consists of the outer membrane and the inner membrane. The inner membrane is subdivided into the inner boundary membrane that runs parallel to the outer membrane and the crista membrane. Both sections of the inner membrane are linked by crista junctions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28275059/differences-in-post-injury-auditory-system-pathophysiology-after-mild-blast-and-non-blast-acute-acoustic-trauma
#20
Nicholas Race, Jesyin Lai, Riyi Shi, Edward L Bartlett
Hearing difficulties are the most commonly reported disabilities among veterans. Blast exposures during explosive events likely play a role, given their propensity to directly damage both peripheral (PAS) and central (CAS) auditory system components. Post-blast PAS pathophysiology has been well-documented in both clinical case reports and laboratory investigations. In contrast, blast-induced CAS dysfunction remains under-studied, but has been hypothesized to contribute to an array of common veteran behavioral complaints including learning, memory, communication, and emotional regulation...
March 8, 2017: Journal of Neurophysiology
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