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https://www.readbyqxmd.com/read/28100613/dynamic-modulation-of-expression-of-lentiviral-restriction-factors-in-primary-cd4-t-cells-following-siv-infection
#1
Andrew R Rahmberg, Premeela A Rajakumar, James M Billingsley, R Paul Johnson
: Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4+ T cells from peripheral blood and jejunum in rhesus macaques, revealing distinct expression patterns in naïve and memory subsets. In both peripheral blood and jejunum, memory CD4+ T cells expressed higher levels of multiple restriction factors compared with naïve cells...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28095513/changes-in-circulating-b-cell-subsets-associated-with-aging-and-acute-siv-infection-in-rhesus-macaques
#2
W L William Chang, Denise F Gonzalez, Hung T Kieu, Luis D Castillo, Ilhem Messaoudi, Xiaoying Shen, Georgia D Tomaras, Barbara L Shacklett, Peter A Barry, Ellen E Sparger
Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques...
2017: PloS One
https://www.readbyqxmd.com/read/28093272/a-method-for-obtaining-simian-immunodeficiency-virus-rna-sequences-from-laser-capture-microdissected-and-immune-captured-cd68-and-cd163-macrophages-from-frozen-tissue-sections-of-bone-marrow-and-brain
#3
Jaclyn Mallard, Emily Papazian, Caroline Soulas, David J Nolan, Marco Salemi, Kenneth C Williams
Laser capture microdissection (LCM) is used to extract cells or tissue regions for analysis of RNA, DNA or protein. Several methods of LCM are established for different applications, but a protocol for consistently obtaining lentiviral RNA from LCM captured immune cell populations is not described. Obtaining optimal viral RNA for analysis of viral genes from immune-captured cells using immunohistochemistry (IHC) and LCM is challenging. IHC protocols have long antibody incubation times that increase risk of RNA degradation...
January 13, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28077653/characterizing-hiv-1-splicing-using-next-generation-sequencing
#4
Ann Emery, Shuntai Zhou, Elizabeth Pollom, Ronald Swanstrom
: Full-length HIV-1 RNA serves as the genome or as an mRNA, or this RNA undergoes splicing using four donors and ten acceptors to create over 50 physiologically relevant transcripts in two size classes (1.8 kb and 4 kb). We developed an assay using Primer ID-tagged deep sequencing to quantify HIV-1 splicing. Using the NL4-3 lab strain we found that A5 (env/nef) is the most commonly used acceptor (about 50%) with A3 (tat) the least used (about 3%). Two small exons are made when a splice to acceptor A1 or A2 is followed by activation of donor D2 or D3, and the high-level use of D2 and D3 dramatically reduces the amount of vif and vpr transcripts...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077643/efficient-vpu-mediated-tetherin-antagonism-by-an-hiv-1-group-o-strain
#5
Katharina Mack, Kathrin Starz, Daniel Sauter, Simon Langer, Frederic Bibollet-Ruche, Gerald H Learn, Christina M Stürzel, Marie Leoz, Jean-Christophe Plantier, Matthias Geyer, Beatrice H Hahn, Frank Kirchhoff
: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077632/phyloepidemiological-analysis-reveals-that-viral-divergence-led-to-the-paucity-of-sivmus-gsn-mon-infections-in-wild-populations
#6
Fabian Schmidt, Florian Liegeois, Edward J D Greenwood, Matthew LeBreton, James Lester, Luc Deleplancque, Martine Peeters, Avelin Aghokeng, Ubald Tamoufe, Joseph L D Diffo, Jean M Takuo, Nathan D Wolfe, Eric Leroy, François Rouet, Jonathan L Heeney
: Human immunodeficiency virus subtype-1 (HIV-1) is the result of cross-species transmission of simian immunodeficiency virus from chimpanzees (SIVcpz). SIVcpz is a chimeric virus which shares common ancestors with viruses infecting red capped mangabeys and a subset of guenon species. The epidemiology of SIV infection in hominoids is characterized by low prevalence and uneven geographical distribution. Surveys in Cameroon indicated that two closely related members of the guenon species subset, mustached guenons and greater spot-nosed guenons, infected with SIVmus and SIVgsn respectively, have also low rates of SIV infections in their populations...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28075174/analysis-of-sivmac-envelope-specific-antibodies-selected-via-phage-display
#7
Sergio Ita, Mayara Rovariz Agostinho, Katherine Sullivan, Seung Yub Han, Rana Akleh, Welkin Johnson, Ismael Ben Farouck Fofana
We have constructed a single chain Fv (scFv) phage display library from an SIV-infected rhesus macaque that developed unusually high-titer neutralizing antibody responses against tier-3, neutralization-resistant SIVmac239. The library was screened using trimeric (gp140) and monomeric (gp120) forms of the SIVmac239 envelope (Env) glycoprotein. We also cloned variable-heavy and variable-light (VH-VL) antibody fragments from 7 previously described rhesus macaque B-cell lines (BLCL) that produce SIV gp120-specific monoclonal antibodies (mAbs)...
January 11, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28069597/chronic-binge-alcohol-induced-dysregulation-of-mitochondrial-related-genes-in-skeletal-muscle-of-simian-immunodeficiency-virus-infected-rhesus-macaques-at-end-stage-disease
#8
Anthony A Duplanty, Liz Simon, Patricia E Molina
AIMS: Alcohol use disorders are more prevalent in HIV patients than the general population. Both chronic alcohol consumption and HIV infection have been linked to mitochondrial dysregulation; and this is considered an important mechanism in the pathogenesis of muscle myopathy. This study investigated if chronic binge alcohol (CBA) administration impairs the expression of genes involved in mitochondrial homeostasis in SIV-infected macaques. METHODS: Male rhesus macaques were administered daily CBA (to achieve peak blood alcohol concentrations of 50-60 mM within 2 h after start of infusion) or sucrose (SUC) intragastrically 3 months prior to intravenous SIVmac251 inoculation and continued until macaques met criteria for end-stage disease...
January 8, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28067901/targeting-samhd1-with-the-vpx-protein-to-improve-cytarabine-therapy-for-hematological-malignancies
#9
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28060314/analysis-of-simian-immunodeficiency-virus-specific-cd8-t-cells-in-rhesus-macaques-by-peptide-mhc-i-tetramer-staining
#10
Lucas Gonzalez-Nieto, Aline Domingues, Michael Ricciardi, Martin J Gutman, Helen S Maxwell, Nuria Pedreño-Lopez, Varian Bailey, Diogo M Magnani, Mauricio A Martins
Peptide-major histocompatibility complex class I (pMHC-I) tetramers have been an invaluable tool to study CD8(+) T-cell responses. Because these reagents directly bind to T-cell receptors on the surface of CD8(+) T-lymphocytes, fluorochrome-labeled pMHC-I tetramers enable the accurate detection of antigen (Ag)-specific CD8(+) T-cells without the need for in vitro re-stimulation. Moreover, when combined with multi-color flow cytometry, pMHC-I tetramer staining can reveal key aspects of Ag-specific CD8(+) T-cells, including differentiation stage, memory phenotype, and activation status...
December 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28056337/marked-enteropathy-in-an-accelerated-macaque-model-of-aids
#11
Joshua D Croteau, Elizabeth L Engle, Suzanne E Queen, Erin N Shirk, M Christine Zink
Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3(+) T cells, and increased SIV-infected cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28055519/seroprevalence-of-cytomegalovirus-infection-among-a-rural-population-of-c%C3%A3-te-d-ivoire
#12
Augustin Etile Anoh, Arsène Mossoun, Chantal Akoua-Koffi, Emmanuel Couacy-Hymann, Maude Pauly, Siv-Aina Leendertz, Eliezer Kouakou N'goran, Grit Schubert, Sabrina Weiss, Jörg Hofmann, Fabian H Leendertz, Bernhard Ehlers
Human cytomegalovirus (HCMV) is a betaherpesvirus that can be pathogenic to humans. In particular, immunocompromised patients can develop life-threatening symptoms. In the present study, HCMV seroprevalence was investigated in a rural population of Western Côte d'Ivoire. Plasma samples collected from 166 apparently healthy subjects living in 8 villages surrounding the Taï Forest National Park were tested for anti-HCMV immunoglobulin G and M antibody with two commercial enzyme-linked immunosorbent assays. Prevalence of anti-HCMV IgG and IgM antibody was 100% and 5...
January 2017: Viral Immunology
https://www.readbyqxmd.com/read/28051083/the-loss-of-ccr6-and-cd161-cd4-t-cell-homeostasis-contributes-to-disease-progression-in-siv-infected-rhesus-macaques
#13
C S McGary, X Alvarez, S Harrington, B Cervasi, E S Ryan, R I Iriele, S Paganini, J L Harper, K Easley, G Silvestri, A A Ansari, M Lichterfeld, L Micci, M Paiardini
Although previous studies have shown that CD4(+) T cells expressing CCR6 and CD161 are depleted from blood during HIV infection, the mechanisms underlying their loss remain unclear. In this study, we investigated how the homeostasis of CCR6(+) and CD161(+) CD4(+) T cells contributes to SIV disease progression and the mechanisms responsible for their loss from circulation. By comparing SIV infection in rhesus macaques (RMs) and natural host sooty mangabeys (SMs), we found that the loss of CCR6(+) and CD161(+) CD4(+) T cells from circulation is a distinguishing feature of progressive SIV infection in RMs...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28050688/high-prevalences-and-a-wide-genetic-diversity-of-simian-retroviruses-in-non-human-primate-bushmeat-in-rural-areas-of-the-democratic-republic-of-congo
#14
Ahuka-Mundeke Steve, Ayouba Ahidjo, Mbala-Kingebeni Placide, Foncelle Caroline, Mubonga Mukulumanya, Ndimbo-Kumugo Simon-Pierre, Lunguya-Metila Octavie, Mbenzo-Abokome Valentin, Muyembe-Tamfum Jean-Jacques, Delaporte Eric, Peeters Martine
Like the majority of emerging infectious diseases, HIV and HTLV are of zoonotic origin. Here we assess the risk of cross-species transmissions of their simian counterparts, SIV and STLV, from non-human primates (NHP) to humans in the Democratic Republic of Congo (DRC). A total of 331 samples, derived from NHP bushmeat, were collected as dried blood spots (DBS, n = 283) or as tissue samples (n = 36) at remote forest sites mainly in northern and eastern DRC. SIV antibody prevalences in DBS were estimated with a novel high throughput immunoassay with antigens representing the actual known diversity of HIV/SIV lineages...
January 3, 2017: EcoHealth
https://www.readbyqxmd.com/read/28039284/defining-categories-of-actionability-for-secondary-findings-in-next-generation-sequencing
#15
Celine Moret, Alex Mauron, Siv Fokstuen, Periklis Makrythanasis, Samia A Hurst
Next-generation sequencing is increasingly used in clinical practice for the diagnosis of Mendelian diseases. Because of the high likelihood of secondary findings associated with this technique, the process of informing patients is beset with new challenges. One of them is regarding the type of secondary findings that ought to be disclosed to patients. The aim of this research is to propose a practical implementation of the notion of actionability, a common criteria justifying the disclosure of secondary findings but whose interpretation varies greatly among professionals...
December 30, 2016: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28036372/collapse-of-cytolytic-potential-in-siv-specific-cd8-t-cells-following-acute-siv-infection-in-rhesus-macaques
#16
Emily R Roberts, Diane G Carnathan, Hui Li, George M Shaw, Guido Silvestri, Michael R Betts
Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM) SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/28034301/mechanistic-differences-between-hiv-1-and-siv-nucleocapsid-proteins-and-cross-species-hiv-1-genomic-rna-recognition
#17
Klara Post, Erik D Olson, M Nabuan Naufer, Robert J Gorelick, Ioulia Rouzina, Mark C Williams, Karin Musier-Forsyth, Judith G Levin
BACKGROUND: The nucleocapsid (NC) domain of HIV-1 Gag is responsible for specific recognition and packaging of genomic RNA (gRNA) into new viral particles. This occurs through specific interactions between the Gag NC domain and the Psi packaging signal in gRNA. In addition to this critical function, NC proteins are also nucleic acid (NA) chaperone proteins that facilitate NA rearrangements during reverse transcription. Although the interaction with Psi and chaperone activity of HIV-1 NC have been well characterized in vitro, little is known about simian immunodeficiency virus (SIV) NC...
December 29, 2016: Retrovirology
https://www.readbyqxmd.com/read/28027596/implementing-pharmacogenomics-in-europe-design-and-implementation-strategy-of-the-ubiquitous-pharmacogenomics-consortium
#18
Cathelijne H van der Wouden, Anne Cambon-Thomsen, Erika Cecchin, Ka-Chun Cheung, Cristina Lucía Dávila-Fajardo, Vera H Deneer, Vita Dolžan, Magnus Ingelman-Sundberg, Siv Jönsson, Mats O Karlsson, Marjolein Kriek, Christina Mitropoulou, George P Patrinos, Munir Pirmohamed, Matthias Samwald, Elke Schaeffeler, Matthias Schwab, Daniela Steinberger, Julia Stingl, Gere Sunder-Plassmann, Giuseppe Toffoli, Richard M Turner, Mandy H van Rhenen, Jesse J Swen, Henk-Jan Guchelaar
Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programmes have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs...
December 27, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28027479/characterization-of-founder-viruses-in-very-early-siv-rectal-transmission
#19
Zhe Yuan, Fangrui Ma, Andrew J Demers, Dong Wang, Jianqing Xu, Mark G Lewis, Qingsheng Li
: A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum...
December 24, 2016: Virology
https://www.readbyqxmd.com/read/28009092/arthritis-management-in-primary-care-a-study-of-physiotherapists-current-practice-educational-needs-and-adherence-to-national-guidelines
#20
Siv Folkhammar Andersson, Stefan Bergman, Elisabet Welin Henriksson, Ann Bremander
BACKGROUND: With an increasing number of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) in primary care, our aim was to investigate arthritis-related practice in physiotherapy and to study adherence to evidence-based care. METHODS: Seventy physiotherapists (PTs) working in primary care were emailed a questionnaire to investigate current practice and the number of roles assumed by PTs, the degree of confidence, educational needs and adherence to national guidelines in managing patients with OA or RA...
December 23, 2016: Musculoskeletal Care
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