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https://www.readbyqxmd.com/read/28734175/cd8-t-cell-programming-by-cytomegalovirus-vectors-applications-in-prophylactic-and-therapeutic-vaccination
#1
REVIEW
Klaus Früh, Louis Picker
Vectors based on cytomegalovirus (CMV) represent a novel vaccine platform that maintains high frequencies of non-exhausted effector memory T cells in both CMV sero-positive and sero-negative individuals. In non-human primate models, CMV vectored vaccines provide unprecedented protection against simian immunodeficiency virus (SIV). Moreover, CMV vectors can be genetically altered to program highly diverse CD8+ T cell responses that differ in their epitope targeting including conventional, MHC-I restricted CD8+ T cells as well as unconventional CD8+ T cells restricted by MHC class II or non-polymorphic MHC-E...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732035/vaccine-induced-immune-responses-against-both-gag-and-env-improve-control-of-simian-immunodeficiency-virus-replication-in-rectally-challenged-rhesus-macaques
#2
Mauricio A Martins, Young C Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J Gutman, Helen S Maxwell, Iris Castro, Diogo M Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D Altman, Matthias Pauthner, Dennis R Burton, Benjamin von Bredow, David T Evans, Maoli Yuan, Christopher L Parks, Keisuke Ejima, David B Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D Lifson, Ronald C Desrosiers, David I Watkins
The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4)...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28708886/kir3dl01-upregulation-on-gut-natural-killer-cells-in-response-to-siv-infection-of-kir-and-mhc-class-i-defined-rhesus-macaques
#3
Moritz Ries, Matthew R Reynolds, Ksenia Bashkueva, Kristin Crosno, Saverio Capuano, Trent M Prall, Roger Wiseman, David H O'Connor, Eva G Rakasz, Hajime Uno, Jeffrey D Lifson, David T Evans
Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28695289/the-role-of-mhc-class-i-gene-products-in-siv-infection-of-macaques
#4
REVIEW
Zachary A Silver, David I Watkins
Human immunodeficiency virus (HIV) remains among the most significant public health threats worldwide. Despite three decades of research following the discovery of HIV, a preventive vaccine remains elusive. The study of HIV elite controllers has been crucial to elaborate the genetic and immunologic determinants that underlie control of HIV replication. Coordinated studies of elite control in humans have, however, been limited by variability among infecting viral strains, host genotype, and the uncertainty of the timing and route of infection...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28692537/early-initiation-of-antiretroviral-treatment-post-siv-infection-does-not-resolve-lymphoid-tissue-activation
#5
Jung Joo Hong, Eduardo L V Silveira, Praveen K Amancha, Siddappa N Byrareddy, Sanjeev Gumber, Kyu-Tae Chang, Aftab A Ansari, Francois Villinger
OBJECTIVE: Germinal center (GC) resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/SIV replication. But the dynamics of GCs upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post SIV infection are not fully understood. DESIGN: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks post infection/pre ART, 6 and 12 weeks following ART initiation...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28691640/design-of-the-fins-teens-study-a-randomized-controlled-trial-assessing-the-impact-of-fatty-fish-on-cognitive-performance-in-adolescents
#6
Siv Skotheim, Lisbeth Dahl, Katina Handeland, Livar Frøyland, Øyvind Lie, Jannike Øyen, Marian Kjellevold, Kjell Morten Stormark, Ingvild Eide Graff
AIMS: To describe the rationale, study design, population and dietary compliance in a randomized controlled trial (RCT) investigating the effect of fatty fish on cognitive performance and mental health in adolescents. METHOD: In the Fish Intervention Studies-TEENS (FINS-TEENS) study we individually randomized 478 adolescents (14-15-year-olds) from eight secondary schools in Norway to receive school meal lunches with fatty fish or meat or n-3 supplements three times a week for 12 weeks...
July 1, 2017: Scandinavian Journal of Public Health
https://www.readbyqxmd.com/read/28687795/the-anti-hiv-candidate-abx464-dampens-intestinal-inflammation-by-triggering-il-22-production-in-activated-macrophages
#7
Karim Chebli, Laura Papon, Conception Paul, Aude Garcel, Noëlie Campos, Didier Scherrer, Hartmut J Ehrlich, Michael Hahne, Jamal Tazi
The progression of human immunodeficiency virus (HIV) is associated with mucosal damage in the gastrointestinal (GI) tract. This damage enables bacterial translocation from the gut and leads to subsequent inflammation. Dextran sulfate sodium (DSS-exposure) is an established animal model for experimental colitis that was recently shown to recapitulate the link between GI-tract damage and pathogenic features of SIV infection. The current study tested the protective properties of ABX464, a first-in-class anti-HIV drug candidate currently in phase II clinical trials...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685417/the-lymph-node-in-hiv-pathogenesis
#8
REVIEW
Yiannis Dimopoulos, Eirini Moysi, Constantinos Petrovas
Lymph nodes play a central role in the development of adaptive immunity against pathogens and particularly the generation of antigen-specific B cell responses in specialized areas called germinal centers (GCs). Lymph node (LN) pathology was recognized as an important consequence of human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. Investigation into the structural and functional alterations induced by HIV and Simian immunodeficiency virus (SIV) has further cemented the central role that lymphoid tissue plays in HIV/SIV pathogenesis...
July 7, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28680241/stochastic-inequalities-and-applications-to-dynamics-analysis-of-a-novel-sivs-epidemic-model-with-jumps
#9
Xiaona Leng, Tao Feng, Xinzhu Meng
This paper proposes a new nonlinear stochastic SIVS epidemic model with double epidemic hypothesis and Lévy jumps. The main purpose of this paper is to investigate the threshold dynamics of the stochastic SIVS epidemic model. By using the technique of a series of stochastic inequalities, we obtain sufficient conditions for the persistence in mean and extinction of the stochastic system and the threshold which governs the extinction and the spread of the epidemic diseases. Finally, this paper describes the results of numerical simulations investigating the dynamical effects of stochastic disturbance...
2017: Journal of Inequalities and Applications
https://www.readbyqxmd.com/read/28679752/sivmac239-but-not-sivmac316-binds-and-utilizes-human-cd4-more-efficiently-than-rhesus-cd4
#10
Christoph H Fellinger, Matthew R Gardner, Charles C Bailey, Michael Farzan
Rhesus macaques are used to model HIV-1 infections, but they are not natural hosts of HIV-1 or any simian immunodeficiency virus (SIV). Rather, they became infected with SIV through cross-species transfer from sooty mangabeys in captivity. It has been shown that HIV-1 utilizes rhesus CD4 less efficiently than human CD4. However, the relative ability of SIV envelope glycoproteins to bind or utilize these CD4 orthologs has not been described. Here we show that several SIV isolates, including SIVmac239, are more efficiently neutralized by human CD4-Ig (huCD4-Ig) than by the same molecule bearing rhesus CD4 domains 1 and 2 (rhCD4-Ig)...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28672035/modern-day-siv-viral-diversity-generated-by-extensive-recombination-and-cross-species-transmission
#11
Sidney M Bell, Trevor Bedford
Cross-species transmission (CST) has led to many devastating epidemics, but is still a poorly understood phenomenon. HIV-1 and HIV-2 (human immunodeficiency virus 1 and 2), which have collectively caused over 35 million deaths, are the result of multiple CSTs from chimpanzees, gorillas, and sooty mangabeys. While the immediate history of HIV is known, there are over 45 lentiviruses that infect specific species of primates, and patterns of host switching are not well characterized. We thus took a phylogenetic approach to better understand the natural history of SIV recombination and CST...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28671330/cytomegaloviral-hypophysitis-in-a-simian-immunodeficiency-virus-infected-rhesus-macaque-macacca-mulatta
#12
Melissa R Berg, Michael A Owston, Marie-Claire Gauduin, Basel T Assaf, Anne D Lewis, Edward J Dick
Rhesus macaques experimentally infected with Simian Immunodeficiency Virus (SIV) experience immunosuppression and often opportunistic infection. Among the most common opportunistic infections are rhesus cytomegalovirus (RhCMV), a ubiquitous betaherpesvirus that undergoes continuous low-level replication in immunocompetent monkeys. Upon SIV-mediated immunodeficiency, RhCMV reactivates and results in lesions in numerous organ systems including the nervous and reproductive systems. We report the first case of cytomegaloviral hypophysitis in a SIV-immunocompromised rhesus macaque...
July 3, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28667761/persistent-accumulation-of-gut-macrophages-with-impaired-phagocytic-function-correlates-with-siv-disease-progression-in-macaques
#13
Zachary D Swan, Anthea L Bouwer, Elizabeth R Wonderlich, Simon M Barratt-Boyes
The contribution of macrophages in the gastrointestinal tract to disease control or progression in HIV infection remains unclear. To address this question, we analyzed CD163(+) macrophages in ileum and mesenteric lymph nodes (LN) from SIV-infected rhesus macaques with dichotomous expression of controlling MHC class I alleles predicted to be SIV controllers or progressors. Infection induced accumulation of macrophages into gut mucosa in the acute phase that persisted in progressors but was resolved in controllers...
July 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28660888/use-of-a-gamma-2-herpesvirus-as-a-vector-to-deliver-antibodies-to-rhesus-monkeys
#14
G F Bischof, Y C Shin, S P Fuchs, J M Martinez-Navio, W A Lauer, E G Rakasz, R C Desrosiers
The gamma-2 herpesvirus of rhesus monkeys, rhesus monkey rhadinovirus (RRV), persists principally in B cells of its host. We constructed recombinant strains of RRV expressing the rhesus monkey-derived anti-SIV monoclonal antibodies 4L6 and 5L7 and compared the RRV-mediated in vivo delivery of these antibodies in rhesus monkeys with previous studies that utilized intramuscular delivery with an adeno-associated virus (AAV) vector. Recombinant RRV-4L6 and RRV-5L7 were both shown to stably produce the antibodies in persistently infected B-cell lines in culture...
June 29, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28654687/combined-single-cell-quantitation-of-host-and-siv-genes-and-proteins-ex-vivo-reveals-host-pathogen-interactions-in-individual-cells
#15
Diane L Bolton, Kathleen McGinnis, Greg Finak, Pratip Chattopadhyay, Raphael Gottardo, Mario Roederer
CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28637658/decreased-myoblast-differentiation-in-chronic-binge-alcohol-administered-simian-immunodeficiency-virus-infected-male-macaques-role-of-decreased-mir-206
#16
Liz Simon, Stephen M Ford, Kejing Song, Paul Berner, Curtis Vande Stouwe, Steve Nelson, Gregory J Bagby, Patricia E Molina
Skeletal muscle stem cells play a critical role in regeneration of myofibers. We have previously demonstrated that chronic binge alcohol (CBA) markedly attenuates myoblast differentiation potential and myogenic gene expression. Muscle specific microRNAs are implicated in regulating myogenic genes. The aim of this study was to determine whether myoblasts isolated from asymptomatic CBA administered SIV-infected macaques treated with antiretroviral therapy (ART) showed similar impairments and if so, to elucidate potential underlying mechanisms...
June 21, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28636599/addendum-immune-clearance-of-highly-pathogenic-siv-infection
#17
Scott G Hansen, Michael Piatak, Abigail B Ventura, Colette M Hughes, Roxanne M Gilbride, Julia C Ford, Kelli Oswald, Rebecca Shoemaker, Yuan Li, Matthew S Lewis, Awbrey N Gilliam, Guangwu Xu, Nathan Whizin, Benjamin J Burwitz, Shannon L Planer, John M Turner, Alfred W Legasse, Michael K Axthelm, Jay A Nelson, Klaus Früh, Jonah B Sacha, Jacob D Estes, Brandon F Keele, Paul T Edlefsen, Jeffrey D Lifson, Louis J Picker
This corrects the article DOI: 10.1038/nature12519.
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28623393/limited-mhc-class-i-intron-2-repertoire-variation-in-bonobos
#18
Natasja G de Groot, Corrine M C Heijmans, Philippe Helsen, Nel Otting, Zjef Pereboom, Jeroen M G Stevens, Ronald E Bontrop
Common chimpanzees (Pan troglodytes) experienced a selective sweep, probably caused by a SIV-like virus, which targeted their MHC class I repertoire. Based on MHC class I intron 2 data analyses, this selective sweep took place about 2-3 million years ago. As a consequence, common chimpanzees have a skewed MHC class I repertoire that is enriched for allotypes that are able to recognise conserved regions of the SIV proteome. The bonobo (Pan paniscus) shared an ancestor with common chimpanzees approximately 1...
June 16, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28615155/experiences-from-developing-and-upgrading-a-web-based-surveillance-system-for-malaria-elimination-in-cambodia
#19
Clementine Fu, Sérgio Lopes, Steve Mellor, Siddhi Aryal, Siv Sovannaroth, Arantxa Roca-Feltrer
Strengthening the surveillance component is key toward achieving country-wide malaria elimination in Cambodia. A Web-based upgraded malaria information system (MIS) was deemed to essentially act as the central component for surveillance strengthening. New functionality (eg, data visualization) and operational (eg, data quality) attributes of the system received particular attention. However, building from the lessons learned in previous systems' developments, other aspects unique to Cambodia were considered to be equally important; for instance, feasibility issues, particularly at the field level (eg, user acceptability at various health levels), and sustainability needs (eg, long-term system flexibility)...
June 14, 2017: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/28613827/tuning-metabolome-coverage-in-reversed-phase-lc-ms-metabolomics-of-meoh-extracted-samples-using-the-reconstitution-solvent-composition
#20
Anna Lindahl, Siv Sääf, Janne Lehtiö, Anders Nordström
Considering the physicochemical diversity of the metabolome, untargeted metabolomics will inevitably discriminate against certain compound classes. Efforts are nevertheless made to maximize the metabolome coverage. Contrary to the main steps of a typical liquid chromatography-mass spectrometry (LC-MS) metabolomics workflow, such as metabolite extraction, the sample reconstitution step has not been optimized for maximal metabolome coverage. This sample concentration step typically occurs after metabolite extraction, when dried samples are reconstituted in a solvent for injection on column...
June 28, 2017: Analytical Chemistry
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