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https://www.readbyqxmd.com/read/28230645/clinical-scale-rapid-autologous-bk-virus-specific-t-cell-line-generation-from-kidney-transplant-recipients-with-active-viremia-for-adoptive-immunotherapy
#1
Caroline Lamarche, Julie Orio, Victoria Georges-Tobar, Thomas Pincez, Mathieu Goupil, Amina Dahmani, Cedric Carli C, Ann Brasey, Lambert Busque, Jean-Sébastien Delisle
BACKGROUND: Polyomavirus-associated nephropathy (PVAN) following BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulation/expansion offers the possibility to generate BK-specific T cell lines for adoptive immunotherapy. The objective of this study was to develop and characterize a clinical scale protocol to generate BK-specific T cell lines from viremic KTR...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#2
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28225767/interferon-%C3%AE-1a-for-the-treatment-of-ebola-virus-disease-a-historically-controlled-single-arm-proof-of-concept-trial
#3
Mandy Kader Konde, Darren P Baker, Fode Amara Traore, Mamadou Saliou Sow, Alioune Camara, Alpha Amadou Barry, Doussou Mara, Abdoulaye Barry, Moussa Cone, Ibrahima Kaba, Amento Ablam Richard, Abdoul Habib Beavogui, Stephan Günther, Melania Pintilie, Eleanor N Fish
To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit...
2017: PloS One
https://www.readbyqxmd.com/read/28223458/mutation-of-the-n-terminal-region-of-chikungunya-virus-capsid-protein-implications-for-vaccine-design
#4
Adam Taylor, Xiang Liu, Ali Zaid, Lucas Y H Goh, Jody Hobson-Peters, Roy A Hall, Andres Merits, Suresh Mahalingam
Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the Togaviridae family responsible for frequent outbreaks of arthritic disease in humans. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleolus. In encephalitic alphaviruses, nuclear translocation induces host cell transcriptional shutoff; however, the role of capsid protein nucleolar localization in arthritogenic alphaviruses remains unclear. Using recombinant enhanced green fluorescent protein (EGFP)-tagged expression constructs and CHIKV infectious clones, we describe a nucleolar localization sequence (NoLS) in the N-terminal region of capsid protein, previously uncharacterized in CHIKV...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28222180/pre-existing-neutralizing-antibody-mitigates-b-cell-dysregulation-and-enhances-the-env-specific-antibody-response-in-shiv-infected-rhesus-macaques
#5
Juan Pablo Jaworski, Peter Bryk, Zachary Brower, Bo Zheng, Ann J Hessell, Alexander F Rosenberg, Tong Tong Wu, Ignacio Sanz, Michael C Keefer, Nancy L Haigwood, James J Kobie
Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28220254/hiv-1-persistent-viremia-is-frequently-followed-by-episodes-of-low-level-viremia
#6
Marek Widera, Miriam Dirks, Barbara Bleekmann, Robert Jablonka, Martin Däumer, Hauke Walter, Robert Ehret, Jens Verheyen, Stefan Esser
After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed...
February 20, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28211903/activating-killer-immunoglobulin-receptors-and-hla-c-a-successful-combination-providing-hiv-1-control
#7
Mauro S Malnati, Elisabetta Ugolotti, Maria Cristina Monti, Davide De Battista, Irene Vanni, Domenico Bordo, Francesca Sironi, Patrizia Larghero, Eddi Di Marco, Priscilla Biswas, Guido Poli, Elisa Vicenzi, Agostino Riva, Maciej Tarkowski, Giuseppe Tambussi, Silvia Nozza, Gino Tripodi, Francesco Marras, Andrea De Maria, Angela Pistorio, Roberto Biassoni
Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211192/racial-differences-in-incident-de-novo-donor-specific-anti-hla-antibody-among-primary-renal-allograft-recipients
#8
Matthew J Everly, Kimberly P Briley, Carl E Haisch, Georg Dieplinger, Paul Bolin, Scott A Kendrick, Claire Morgan, Angela Q Maldonado, Lorita M Rebellato
Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA-mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre- and post-transplant and tested for anti-HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non-AA), 107 developed dnDSA at a median of 9...
February 17, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28209877/peak-hiv-viremia-pushes-cd8-t-cells
#9
EDITORIAL
Lindsey Pujanandez
No abstract text is available yet for this article.
February 17, 2017: Science
https://www.readbyqxmd.com/read/28208002/expression-of-hepatocyte-hepatitis-b-core-antigen-and-hepatitis-b-surface-antigen-as-a-marker-in-the-management-of-chronic-hepatitis-b-patients
#10
Sun Young Yim, Tae Hyung Kim, Suh Sang Jun, Eun Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Yoon Tae Jeen, Hoon Jai Chun, Hong Sik Lee, Soon Ho Um, Chang Duck Kim, Nam Hee Won, Ho Sang Ryu
Background/Aims: We aimed to clarify the association of HBsAg/HBcAg with the disease status and treatment response in patients with chronic hepatitis B (CHB). Methods: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 HBeAg-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous...
February 17, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28207975/stabilization-of-renal-function-after-the-first-year-of-follow-up-in-kidney-transplant-recipients-treated-for-significant-bk-polyomavirus-infection-or-bk-polyomavirus-associated-nephropathy
#11
Marie-Christine Simard-Meilleur, Paule Bodson-Clermont, Gilles St-Louis, Michel R Pâquet, Catherine Girardin, Marie-Chantal Fortin, Héloïse Cardinal, Marie-Josée Hébert, Reneé Lévesque, Edith Renoult
BACKGROUND: BK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV-associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow-up periods. METHODS: We reviewed the outcome of our screening and immunosuppression reduction protocol in 305 patients who received a kidney transplant between March 2008 and January 2013...
February 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28207500/strategic-use-of-dual-regimens-of-boosted-protease-inhibitors-plus-maraviroc-in-poorly-adherent-subjects-in-view-of-long-acting-drugs-a-retrospective-study
#12
Amedeo Ferdinando Capetti, Mariangela Micale, Laura Carenzi, Fosca Niero, Simona Landonio, Stefania Vimercati, Gianfranco Dedivitiis, Giuliano Rizzardini
In view of the forthcoming long-acting antiretrovirals, measures should be taken to prevent the selection of HIV drug resistance mutations. All subjects who had been switched to boosted protease inhibitors plus maraviroc (bPIs/MVC) with baseline HIV-1 RNA >50 copies/mL between June, 2014, and April, 2015, were retrospectively evaluated. HIV-1 RNA, CD4+ T-cells, serum glucose, creatinine, ALT, and adverse events were controlled every 3 to 4 months. We retrospectively analyzed 44 patients: 18 were taking darunavir/ritonavir (DRV/r) and 26 atazanavir/ritonavir (ATV/r) once daily, plus MVC 300 mg once daily...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207489/b-cell-abnormalities-and-impact-on-antibody-response-in-hiv-infection
#13
Alessandra Noto, Giuseppe Pantaleo
PURPOSE OF REVIEW: The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection. RECENT FINDINGS: Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env)...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28202771/delayed-differentiation-of-potent-effector-cd8-t-cells-reducing-viremia-and-reservoir-seeding-in-acute-hiv-infection
#14
Hiroshi Takata, Supranee Buranapraditkun, Cari Kessing, James L K Fletcher, Roshell Muir, Virginie Tardif, Pearline Cartwright, Claire Vandergeeten, Wendy Bakeman, Carmen N Nichols, Suteeraporn Pinyakorn, Pokrath Hansasuta, Eugene Kroon, Thep Chalermchai, Robert O'Connell, Jerome Kim, Nittaya Phanuphak, Merlin L Robb, Nelson L Michael, Nicolas Chomont, Elias K Haddad, Jintanat Ananworanich, Lydie Trautmann
CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI)...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28202759/relationship-between-measures-of-hiv-reactivation-and-the-decline-of-latent-reservoir-under-latency-reversing-agents
#15
Janka Petravic, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latency-reversing agents (LRA) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRA are explored in clinical trials, it becomes increasingly important to assess the effect of increased HIV reactivation rate on the decline of latently infected cells, and estimate LRA efficacy in increasing virus reactivation...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28198350/cerebrospinal-fluid-viral-load-and-neopterin-in-hiv-positive-patients-with-undetectable-viraemia
#16
Ilaria Motta, Tiziano Allice, Alessandra Romito, Micol Ferrara, Sara Ecclesia, Daniele Imperiale, Valeria Ghisetti, Giovanni Di Perri, Stefano Bonora, Andrea Calcagno
BACKGROUND: Cerebrospinal fluid (CSF) HIV RNA is commonly used as a marker of compartmental antiviral activity in HIV-positive patients. Undetectable CSF HIV RNA levels have been associated with low CSF neopterin levels and better neurocognitive performances. Aim of this study was to analyse the prevalence and predictors of non-detectable CSF HIV RNA using a commercial assay. METHODS: In adult HIV-positive HAART-treated patients with confirmed plasma HIV RNA <50 copies/mL, CSF HIV RNA (with Roche Amplicor Assay) and neopterin were measured...
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28196049/hiv-infection-in-the-native-and-allograft-kidney-implications-for-management-diagnosis-and-transplantation
#17
Véronique Avettand-Fenoël, Christine Rouzioux, Christophe Legendre, Guillaume Canaud
The native kidney is a reservoir for HIV-1 and a site of viral replication, similar to lymphoid tissue, gut-associated lymphoid tissue or semen. The ability of the virus to persist may result from either a true latency or sequestration in an anatomic site that is not effectively exposed to antiretroviral therapy. The presence of HIV in kidney epithelial cells will lead progressively to end-stage renal disease. For decades, HIV-infected patients were excluded from consideration for kidney transplantation. Hemodialysis and peritoneal dialysis were the only forms of treatment available to these patients...
February 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28194857/hepatitis-e-risks-pigs-or-blood-that-is-the-question
#18
Richard S Tedder, Samreen Ijaz, Alan Kitchen, Ines Ushiro-Lumb, Kate I Tettmar, Patricia Hewitt, Nick Andrews
BACKGROUND: Infection with hepatitis E virus (HEV) Genotype 3 is recognized as a food-borne zoonosis in developed countries where it usually causes a mild self-limited acute hepatitis. It may cause a persistent infection in the immunosuppressed human that can progress to cirrhosis. To protect the patient from transfusion-acquired HEV infection, steps have been taken in the United Kingdom to provide for at-risk patients only components from donors screened for HEV viremia. This strategy does not protect from dietary exposure and calls into question estimation of relative risk between blood transfusion and diet...
February 2017: Transfusion
https://www.readbyqxmd.com/read/28192453/refining-criteria-for-selecting-candidates-for-a-safe-lopinavir-ritonavir-or-darunavir-ritonavir-monotherapy-in-hiv-infected-virologically-suppressed-patients
#19
Nicola Gianotti, Alessandro Cozzi-Lepri, Andrea Antinori, Antonella Castagna, Andrea De Luca, Benedetto Maurizio Celesia, Massimo Galli, Cristina Mussini, Carmela Pinnetti, Vincenzo Spagnuolo, Antonella d'Arminio Monforte, Francesca Ceccherini-Silberstein, Massimo Andreoni
OBJECTIVE: The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). DESIGN: A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. METHODS: VL was assessed in each center according to local procedures...
2017: PloS One
https://www.readbyqxmd.com/read/28191297/leishmania-infantum-and-epstein-barr-virus-co-infection-in-a-patient-with-hemophagocytosis
#20
Zied Gaifer, Mohamed-Rachid Boulassel
The authors describe a rare case of a 27- year old previously healthy male presenting with high grade fever, pancytopenia, hepatosplenomegaly, high levels of ferritin and triglyceride, suggesting a diagnosis of hemophagocytic lymphohistiocytosis (HLH) syndrome. Other investigations showed a positive Leishmania infantum serology and high Epstein-Barr virus (EBV) viremia. The diagnosis of a visceral leishmaniasis was confirmed by bone morrow biopsy, which showed Leishman-Donovan bodies and evidence of HLH. The patient received liposomal amphotericin B and he had a complete resolution of his symptoms and clearance of EBV viremia...
December 31, 2016: Infectious Disease Reports
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