by Molly Ohainle, Kyusik Kim, Sevnur Komurlu Keceli, Abby Felton, Ed Campbell, Jeremy Luban, Michael Emerman The HIV-1 capsid protein makes up the core of the virion and plays a critical role in early steps of HIV replication. Due to its exposure in the cytoplasm after entry, HIV capsid is a target for host cell factors that act directly to block infection such as TRIM5α and MxB. Several host proteins also play a role in facilitating infection, including in the protection of HIV-1 capsid from...
by Heather A. Flores, Jyotika Taneja de Bruyne, Tanya B. O’Donnell, Vu Tuyet Nhu, Nguyen Thi Giang, Huynh Thi Xuan Trang, Huynh Thi Thuy Van, Vo Thi Long, Le Thi Dui, Huynh Le Anh Huy, Huynh Thi Le Duyen, Nguyen Thi Van Thuy, Nguyen Thanh Phong, Nguyen Van Vinh Chau, Duong Thi Hue Kien, Tran Thuy Vi, Bridget Wills, Scott L. O’Neill, Cameron P. Simmons, Lauren B. Carrington The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against...
by Shauna M. Crowley, Xiao Han, Joannie M. Allaire, Martin Stahl, Isabella Rauch, Leigh A. Knodler, Bruce A. Vallance We investigated the role of the inflammasome effector caspases-1 and -11 during Salmonella enterica serovar Typhimurium infection of murine intestinal epithelial cells (IECs). Salmonella burdens were significantly greater in the intestines of caspase-1/11 deficient (Casp1/11−/−), Casp1−/− and Casp11−/− mice, as compared to wildtype mice. To determine if this reflected IEC-intrinsic...
by Camille Rey, Yuen-Yan Chang, Patricia Latour-Lambert, Hugo Varet, Caroline Proux, Rachel Legendre, Jean-Yves Coppée, Jost Enninga Microfold (M) cell host-pathogen interaction studies would benefit from the visual analysis of dynamic cellular and microbial interplays. We adapted a human in vitro M cell model to physiological bacterial infections, expression of fluorescent localization reporters and long-term three-dimensional time-lapse microscopy. This approach allows following key steps...
by Michael D. Lewis, Andrea Paun, Audrey Romano, Harry Langston, Charlotte A. Langner, Ian N. Moore, Kevin W. Bock, Amanda Fortes Francisco, Jason M. Brenchley, David L. Sacks Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the...
by Liling Shan, Shuang Li, Jan Meeldijk, Bernadet Blijenberg, Astrid Hendriks, Karlijn J. W. M. van Boxtel, Sara P. H. van den Berg, Ian J. Groves, Martin Potts, Adriana Svrlanska, Thomas Stamminger, Mark R. Wills, Niels Bovenschen Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and can trigger devastating disease in immune-suppressed patients. Cytotoxic lymphocytes (CD8+ T cells and NK cells) control HCMV infection by releasing interferon-γ and five granzymes...
by Athar Alam, Igor Golovliov, Eram Javed, Rajender Kumar, Jörgen Ådén, Anders Sjöstedt Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for its virulence. The chaperone ClpB, a member of the Hsp100/Clp family, is involved in Francisella T6SS disassembly and type VI secretion (T6S) is impaired in its absence. We asked if the role of ClpB for T6S was related to its prototypical role for the disaggregation...
by Charlotte A. Scarff, Rebecca F. Thompson, George F. J. Newlands, Alexander. H. Jamson, Christopher Kennaway, Vivian J. da Silva, Elida M. Rabelo, Chun-Feng Song, John Trinick, W. David Smith, Stephen P. Muench Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination...
by Robert W. P. Glowacki, Eric C. Martens
by R. Christopher D. Furniss, Markus Kostrzewa, Despoina A. I. Mavridou, Gerald Larrouy-Maumus
by Raecliffe Daly, Denys A. Khaperskyy, Marta Maria Gaglia
by Jumei Zeng, John Platig, Tan-Yun Cheng, Saima Ahmed, Yara Skaf, Lakshmi-Prasad Potluri, Daniel Schwartz, Hanno Steen, D. Branch Moody, Robert N. Husson The Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB are essential for growth and have been proposed as possible drug targets. We used a titratable conditional depletion system to investigate the functions of these kinases. Depletion of PknA or PknB or both kinases resulted in growth arrest, shortening of cells, and time-dependent...
by William J. Olson, Bruno Martorelli Di Genova, Gina Gallego-Lopez, Anthony R. Dawson, David Stevenson, Daniel Amador-Noguez, Laura J. Knoll The obligate intracellular parasite Toxoplasma gondii is auxotrophic for several key metabolites and must scavenge these from the host. It is unclear how T. gondii manipulates host metabolism to support its overall growth rate and non-essential metabolites. To investigate this question, we measured changes in the joint host-parasite metabolome over a time...
by Ming Li, Christopher B. Ball, Geoffrey Collins, Qiaolin Hu, Donal S. Luse, David H. Price, Jeffery L. Meier Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces...
by Xuan Zhong, Lu Feng, Ru Zang, Cao-Qi Lei, Qing Yang, Hong-Bing Shu The retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5), sense cytoplasmic viral RNA and initiate innate antiviral responses. How RIG-I and MDA5 are differentially regulated remains enigmatic. In this study, we identified the guanylate-binding protein (GBP) and zinc-finger FYVE domain-containing protein ZFYVE1 as a negative regulator of MDA5- but...
by Nicole Caduff, Donal McHugh, Anita Murer, Patrick Rämer, Ana Raykova, Vanessa Landtwing, Lisa Rieble, Christian W. Keller, Michael Prummer, Laurent Hoffmann, Janice K. P. Lam, Alan K. S. Chiang, Friedrich Raulf, Tarik Azzi, Christoph Berger, Tina Rubic-Schneider, Elisabetta Traggiai, Jan D. Lünemann, Michael Kammüller, Christian Münz Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication after organ transplantation frequently associated with the Epstein-Barr...
by Dylan H. de Vries, Vasiliki Matzaraki, Olivier B. Bakker, Harm Brugge, Harm-Jan Westra, Mihai G. Netea, Lude Franke, Vinod Kumar, Monique G. P. van der Wijst Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In the majority of candidemia cases, Candida albicans is responsible. Worryingly, a global increase in the number of patients who are susceptible to infection (e.g. immunocompromised...
by Vincent R. Graziano, Forrest C. Walker, Elizabeth A. Kennedy, Jin Wei, Khalil Ettayebi, Madison S. Strine, Renata B. Filler, Ebrahim Hassan, Leon L. Hsieh, Arthur S. Kim, Abimbola O. Kolawole, Christiane E. Wobus, Lisa C. Lindesmith, Ralph S. Baric, Mary K. Estes, Robert C. Orchard, Megan T. Baldridge, Craig B. Wilen Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism,...
by Shivani Choudhary, Samuel K. Buxton, Sreekanth Puttachary, Saurabh Verma, Gunnar R. Mair, Ciaran J. McCoy, Barbara J. Reaves, Adrian J. Wolstenholme, Richard J. Martin, Alan P. Robertson Nematode parasites infect approximately 1.5 billion people globally and are a significant public health concern. There is an accepted need for new, more effective anthelmintic drugs. Nicotinic acetylcholine receptors on parasite nerve and somatic muscle are targets of the cholinomimetic anthelmintics, while...
by Amy J. Sterling, William J. Snelling, Patrick J. Naughton, Nigel G. Ternan, James S. G. Dooley Enterococci are robust gram-positive bacteria that are found in a variety of surroundings and that cause a significant number of healthcare-associated infections. The genus possesses a high-efficiency pheromone-responsive plasmid (PRP) transfer system for genetic exchange that allows antimicrobial-resistance determinants to spread within bacterial populations. The pCF10 plasmid system is the best...
by Raquel Tarancón, Jorge Domínguez-Andrés, Santiago Uranga, Anaísa V. Ferreira, Laszlo A. Groh, Mirian Domenech, Fernando González-Camacho, Niels P. Riksen, Nacho Aguilo, José Yuste, Carlos Martín, Mihai G. Netea Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific...
by Matthew Esparza, Amir Mor, Hanspeter Niederstrasser, Kris White, Alexander White, Ke Zhang, Shengyan Gao, Juan Wang, Jue Liang, Sei Sho, Ramanavelan Sakthivel, Adwait A. Sathe, Chao Xing, Raquel Muñoz-Moreno, Jerry W. Shay, Adolfo García-Sastre, Joseph Ready, Bruce Posner, Beatriz M. A. Fontoura Influenza A viruses are human pathogens with limited therapeutic options. Therefore, it is crucial to devise strategies for the identification of new classes of antiviral medications. The influenza...
by Jessica R. Galloway-Peña, Dimitrios P. Kontoyiannis
by Justin T. Hsieh, Ashley L. St. John
by Gregory B. Whitfield, Lindsey S. Marmont, Cedoljub Bundalovic-Torma, Erum Razvi, Elyse J. Roach, Cezar M. Khursigara, John Parkinson, P. Lynne Howell Our understanding of the biofilm matrix components utilized by Gram-positive bacteria, and the signalling pathways that regulate their production are largely unknown. In a companion study, we developed a computational pipeline for the unbiased identification of homologous bacterial operons and applied this algorithm to the analysis of synthase-dependent...
by Amanda P. Woon, Victoria Boyd, Shawn Todd, Ina Smith, Reuben Klein, Isaac B. Woodhouse, Sarah Riddell, Gary Crameri, John Bingham, Lin-Fa Wang, Anthony W. Purcell, Deborah Middleton, Michelle L. Baker Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come...
by Jun Luo, Ji Xi, Lu Gao, Jianming Hu Hepatitis B virus (HBV) delivers a partially double-stranded, relaxed circular (RC) DNA genome in complete virions to the host cell nucleus for conversion to the covalently closed circular (CCC) DNA, which establishes and sustains viral infection. An overlength pregenomic RNA (pgRNA) is then transcribed from CCC DNA and packaged into immature nucleocapsids (NCs) by the viral core (HBc) protein. pgRNA is reverse transcribed to produce RC DNA in mature NCs,...
by Julia Sehl, Julia E. Hölper, Barbara G. Klupp, Christina Baumbach, Jens P. Teifke, Thomas C. Mettenleiter Herpesviral encephalitis caused by Herpes Simplex Virus 1 (HSV-1) is one of the most devastating diseases in humans. Patients present with fever, mental status changes or seizures and when untreated, sequelae can be fatal. Herpes Simplex Encephalitis (HSE) is characterized by mainly unilateral necrotizing inflammation effacing the frontal and mesiotemporal lobes with rare involvement...
by Paul David, Malgorzata Drabczyk-Pluta, Eva Pastille, Torben Knuschke, Tanja Werner, Nadine Honke, Dominik A. Megger, Ilseyar Akhmetzyanova, Namir Shaabani, Annette Eyking-Singer, Elke Cario, Olivia Kershaw, Achim D. Gruber, Matthias Tenbusch, Kirsten K. Dietze, Mirko Trilling, Jia Liu, Dirk Schadendorf, Hendrik Streeck, Karl S. Lang, Youhua Xie, Lisa Zimmer, Barbara Sitek, Annette Paschen, Astrid M. Westendorf, Ulf Dittmer, Gennadiy Zelinskyy Combination immunotherapy (CIT) is currently applied...
by Mykhaylo Usyk, Christine P. Zolnik, Philip E. Castle, Carolina Porras, Rolando Herrero, Ana Gradissimo, Paula Gonzalez, Mahboobeh Safaeian, Mark Schiffman, Robert D. Burk, Costa Rica HPV Vaccine Trial (CVT) Group Background Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome...
by Stephanie N. Langel, Claire E. Otero, David R. Martinez, Sallie R. Permar
by Laís Amorim Sacramento, Luciana Benevides, Sandra Regina Maruyama, Lucas Tavares, Kiyoshi Ferreira Fukutani, Marcela Francozo, Tim Sparwasser, Fernando Queiroz Cunha, Roque Pacheco Almeida, João Santana da Silva, Vanessa Carregaro A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined...
by Bo-Ram Kim, Byoung-Jun Kim, Yoon-Hoh Kook, Bum-Joon Kim Mycobacterium abscessus (MAB) is a rapidly growing mycobacterium (RGM), and infections with this pathogen have been increasing worldwide. Recently, we reported that rough type (MAB-R) but not smooth type (MAB-S) strains enhanced type 1 interferon (IFN-I) secretion via bacterial phagosome escape, contributing to increased virulence. Here, we sought to investigate the role of mitochondrial oxidative stress in bacterial survival, IFN-I...
by Sylvie Malembic-Maher, Delphine Desqué, Dima Khalil, Pascal Salar, Bernard Bergey, Jean-Luc Danet, Sybille Duret, Marie-Pierre Dubrana-Ourabah, Laure Beven, Ibolya Ember, Zoltan Acs, Michele Della Bartola, Alberto Materazzi, Luisa Filippin, Slobodan Krnjajic, Oliver Krstić, Ivo Toševski, Friederike Lang, Barbara Jarausch, Maria Kölber, Jelena Jović, Elisa Angelini, Nathalie Arricau-Bouvery, Michael Maixner, Xavier Foissac Flavescence dorée (FD) is a European quarantine grapevine disease transmitted...
Molecular basis of P[II] major human rotavirus VP8* domain recognition of histo-blood group antigens
by Shenyuan Xu, Luay U. Ahmed, Michael Robert Stuckert, Kristen Rose McGinnis, Yang Liu, Ming Tan, Pengwei Huang, Weiming Zhong, Dandan Zhao, Xi Jiang, Michael A. Kennedy Initial cell attachment of rotavirus (RV) to specific cell surface glycan receptors, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors for human RV strains. RV...
by Daniel Pletzer, Evelyn Sun, Caleb Ritchie, Lauren Wilkinson, Leo T. Liu, Michael J. Trimble, Heidi Wolfmeier, Travis M. Blimkie, Robert E. W. Hancock Cystic fibrosis (CF) is a genetic disease that affects mucin-producing body organs such as the lungs. Characteristic of CF is the production of thick, viscous mucus, containing the glycoprotein mucin, that can lead to progressive airway obstruction. Recently, we demonstrated that the presence of mucin induced a rapid surface adaptation in motile...
by Lisa Osbelt, Sophie Thiemann, Nathiana Smit, Till Robin Lesker, Madita Schröter, Eric J. C. Gálvez, Kerstin Schmidt-Hohagen, Marina C. Pils, Sabrina Mühlen, Petra Dersch, Karsten Hiller, Dirk Schlüter, Meina Neumann-Schaal, Till Strowig The composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease severity is largely unknown. Using isogenic mouse lines harboring...
by Jiang Wang, Guo-Li Li, Sheng-Li Ming, Chun-Feng Wang, Li-Juan Shi, Bing-Qian Su, Hong-Tao Wu, Lei Zeng, Ying-Qian Han, Zhong-Hu Liu, Da-Wei Jiang, Yong-Kun Du, Xiang-Dong Li, Gai-Ping Zhang, Guo-Yu Yang, Bei-Bei Chu Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV)...
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