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https://www.readbyqxmd.com/read/29348831/aberrant-expression-of-mir-21-mir-376c-and-mir-145-and-their-target-host-genes-in-merkel-cell-polyomavirus-positive-non-small-cell-lung-cancer
#1
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29343577/cellular-and-humoral-immunity-protect-against-vaginal-zika-virus-infection-in-mice
#2
Jason M Scott, Tania J Lebratti, Justin M Richner, Xiaoping Jiang, Estefania Fernandez, Haiyan Zhao, Daved H Fremont, Michael S Diamond, Haina Shin
Zika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343575/high-resolution-sequencing-of-viral-populations-during-early-siv-infection-reveals-evolutionary-strategies-for-rapid-escape-from-emerging-env-specific-antibody-responses
#3
Sergio Ita, Alison K Hill, Evan C Lam, Fay J Dufort, Xiao Yang, Ruchi Newman, Sivan Leviyang, Ismael B Fofana, Welkin E Johnson
Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV env gene during early infection (≤ 29 weeks post-infection) in a cohort of four SIVmac251-infected rhesus macaques...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#4
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29340211/differences-in-adaptive-dynamics-determine-the-success-of-virus-variants-that-propagate-together
#5
María Arribas, Jacobo Aguirre, Susanna Manrubia, Ester Lázaro
Virus fitness is a complex parameter that results from the interaction of virus-specific characters (e.g. intracellular growth rate, adsorption rate, virion extracellular stability, and tolerance to mutations) with others that depend on the underlying fitness landscape and the internal structure of the whole population. Individual mutants usually have lower fitness values than the complex population from which they come from. When they are propagated and allowed to attain large population sizes for a sufficiently long time, they approach mutation-selection equilibrium with the concomitant fitness gains...
January 2018: Virus Evolution
https://www.readbyqxmd.com/read/29339154/a-new-hepatitis-b-virus-e-antigen-negative-strain-gene-used-as-a-reference-sequence-in-an-animal-model
#6
Min Cao, Zhonghua Zhao, Yuwei Tang, Qinglv Wei, Lei Wang, Qin Xiang, Yunmei Zhang, Huatang Zhang, Guoqi Lai
Infection with hepatitis B virus (HBV) e-antigen (HBeAg)-negative strains is increasingly prevalent. Currently, detailed information of the obtained natural HBV strain is not available except for the B genotype and HBeAg-negative. The aim of the present study was to characterize the natural genetic variation of the HBeAg-negative strain and investigate its function. The genic sequence was determined using Sanger sequencing, and compared to related sequences using alignment and phylogenetic analysis. In vivo, virus-specific serum markers were investigated in CBA/CaJ mice...
January 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#7
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330092/a-novel-double-antigen-sandwich-elisa-for-the-species-independent-detection-of-crimean-congo-hemorrhagic-fever-virus-specific-antibodies
#8
Miriam A Sas, Loic Comtet, Fabien Donnet, Marc Mertens, Zati Vatansever, Noel Tordo, Philippe Pourquier, Martin H Groschup
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease in humans caused by the CCHF virus (CCHFV). The detection of anti-CCHFV antibodies in animals is used to reveal infection risk areas. Therefore a simple, quick and reliable multispecies assay for the detection of CCHFV-specific antibodies is needed. This work presents the development and validation of a novel CCHF double-antigen ELISA for the detection of anti-CCHFV nucleoprotein antibodies. The test requires 30 μl of serum, and results are obtained within 90 min...
January 9, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#9
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29327729/h5n1-influenza-virus-specific-mirna-like-small-rna-increases-cytokine-production-and-mouse-mortality-via-targeting-poly-rc-binding-protein-2
#10
Xihan Li, Zheng Fu, Hongwei Liang, Yanbo Wang, Xian Qi, Meng Ding, Xinlei Sun, Zhen Zhou, Ying Huang, Hongwei Gu, Limin Li, Xi Chen, Donghai Li, Quan Zhao, Fenyong Liu, Hua Wang, Jin Wang, Ke Zen, Chen-Yu Zhang
Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression...
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29321327/human-papillomavirus-16-infection-induces-vap-dependent-endosomal-tubulation
#11
Abida Siddiqa, Paola Massimi, David Pim, Justyna Broniarczyk, Lawrence Banks
Human Papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29311359/the-effects-of-dendritic-cell-hypersensitivity-on-persistent-viral-infection
#12
Jennifer S Tsau, Xin Huang, Chen-Yen Lai, Stephen M Hedrick
Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29309618/single-cell-tracking-reveals-a-role-for-pre-existing-ccr5-memory-th1-cells-in-the-control-of-rhinovirus-a39-after-experimental-challenge-in-humans
#13
Lyndsey M Muehling, Ronald B Turner, Kenneth B Brown, Paul W Wright, James T Patrie, Sampo J Lahtinen, Markus J Lehtinen, William W Kwok, Judith A Woodfolk
Background: Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked circulating CD4+ T cells with identical epitope specificities that responded to intranasal challenge with rhinovirus (RV)-A39, and we assessed T-cell signatures in the nose. Methods: Cells were monitored using a mixture of 2 capsid-specific major histocompatibility complex II tetramers over a 7-week period, before and after RV-A39 challenge, in 16 human leukocyte antigen-DR4+ subjects who participated in a trial of Bifidobacterium lactis (Bl-04) supplementation...
December 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29309050/hepatitis-b-virus-specific-t-cells-associate-with-viral-control-upon-nucleos-t-ide-analogue-therapy-discontinuation
#14
Laura Rivino, Nina Le Bert, Upkar S Gill, Kamini Kunasegaran, Yang Cheng, Damien Zm Tan, Etienne Becht, Navjyot K Hansi, Graham R Foster, Tung-Hung Su, Tai-Chung Tseng, Seng Gee Lim, Jia-Horng Kao, Evan W Newell, Patrick Tf Kennedy, Antonio Bertoletti
BACKGROUND: The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS: Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non-antigen-specific immune populations (NanoString and CyTOF)...
January 8, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29309047/influenza-specific-lung-resident-memory-t-cells-are-proliferative-and-polyfunctional-and-maintain-diverse-tcr-profiles
#15
Angela Pizzolla, Thi Ho Nguyen, Sneha Sant, Jade Jaffar, Tom Loudovaris, Stuart I Mannering, Paul G Thomas, Glen P Westall, Katherine Kedzierska, Linda M Wakim
The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, a highly contagious respiratory pathogen that continues to be a major public health burden. Animal models show that influenza-specific lung CD8+ Trm cells are indispensable for crossprotection against pulmonary infection with different influenza virus strains. However, it is not known whether influenza-specific CD8+ Trm cells present within the human lung have the same critical role in modulating the course of the disease...
January 8, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29305193/ultra-sensitive-droplet-digital-pcr-for-the-assessment-of-microchimerism-in-cellular-therapies
#16
David Kliman, Gloria Castellano-Gonzalez, Barbara Withers, Janine Street, Elizabeth Tegg, Oksana Mirochnik, Joey Lai, Leighton Clancy, David Gottlieb, Emily Blyth
Current techniques to assess chimerism after hematopoietic stem cell transplantation (HSCT) are limited in both sensitivity and precision. These drawbacks are problematic in the context of cellular therapies which frequently result in microchimerism (donor chimerism <1%). We have developed a highly sensitive droplet digital PCR (ddPCR) assay using commercially available regents with good performance throughout the range of clinically relevant chimerism measurements, including microchimerism. We tested the assay using spiked samples of known donor:recipient ratios and in clinical samples from HSCT recipients and patients enrolled on clinical trials of microtransplantation and 3rd party virus specific T cells (VST)...
January 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29305140/innate-like-cytotoxic-function-of-bystander-activated-cd8-t-cells-is-associated-with-liver-injury-in-acute-hepatitis-a
#17
Jihye Kim, Dong-Yeop Chang, Hyun Woong Lee, Hoyoung Lee, Jong Hoon Kim, Pil Soo Sung, Kyung Hwan Kim, Seon-Hui Hong, Wonseok Kang, Jino Lee, So Youn Shin, Hee Tae Yu, Sooseong You, Yoon Seok Choi, Insoo Oh, Dong Ho Lee, Dong Hyeon Lee, Min Kyung Jung, Kyung-Suk Suh, Shin Hwang, Won Kim, Su-Hyung Park, Hyung Joon Kim, Eui-Cheol Shin
Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement...
December 30, 2017: Immunity
https://www.readbyqxmd.com/read/29301753/exosomes-associated-with-human-ovarian-tumors-harbor-a-reversible-checkpoint-of-t-cell-responses
#18
Gautam N Shenoy, Jenni L Loyall, Orla Maguire, Vandana Iyer, Raymond J Kelleher, Hans Minderman, Paul K Wallace, Kunle Odunsi, Sathy V Balu-Iyer, Richard B Bankert
Nano-sized membrane-encapsulated extracellular vesicles isolated from the ascites fluids of ovarian cancer patients are identified as exosomes based on their biophysical and compositional characteristics. We report here that T cells pulsed with these tumor-associated exosomes during TCR-dependent activation inhibit various activation endpoints including translocation of NFkB and NFAT into the nucleus, upregulation of CD69 and CD107a, production of cytokines and cell proliferation. Additionally, the activation of virus-specific CD8+ T cells that are stimulated with the cognate viral peptides presented in the context of class I MHC is also suppressed by the exosomes...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29300297/e3l-and-f1l-gene-functions-modulate-the-protective-capacity-of-modified-vaccinia-virus-ankara-immunization-in-murine-model-of-human-smallpox
#19
Asisa Volz, Sylvia Jany, Astrid Freudenstein, Markus Lantermann, Holger Ludwig, Gerd Sutter
The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice...
January 4, 2018: Viruses
https://www.readbyqxmd.com/read/29296867/long-term-control-of-recurrent-or-refractory-viral-infections-after-allogeneic-hsct-with-third-party-virus-specific-t-cells
#20
Barbara Withers, Emily Blyth, Leighton E Clancy, Agnes Yong, Chris Fraser, Jane Burgess, Renee Simms, Rebecca Brown, David Kliman, Ming-Celine Dubosq, David Bishop, Gaurav Sutrave, Chun Kei Kris Ma, Peter J Shaw, Kenneth P Micklethwaite, David J Gottlieb
Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy...
November 14, 2017: Blood Advances
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