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https://www.readbyqxmd.com/read/29670705/amidate-prodrugs-of-cyclic-9-s-3-hydroxy-2-phosphonomethoxy-propyl-adenine-with-potent-anti-herpesvirus-activity
#1
Min Luo, Elisabetta Groaz, Steven De Jonghe, Robert Snoeck, Graciela Andrei, Piet Herdewijn
A series of amidate prodrugs of cyclic 9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (cHPMPA) featuring different amino acid motifs were synthesized. All phosphonamidates derived from ( S )-cHPMPA displayed a broad spectrum activity against herpesviruses with EC50 values in the low nanomolar range. A phosphonobisamidate prodrug of ( S )-HPMPA also exhibited a remarkably potent antiviral activity. In addition, the leucine ester prodrug of ( S )-cHPMPA and phosphonobisamidate valine ester prodrug of ( S )-HPMPA proved stable in human plasma...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29670408/acute-hepatitis-e-in-a-renal-transplantation-recipient-a-case-report
#2
Mitsutoshi Shindo, Hiroaki Takemae, Takafumi Kubo, Masatsugu Soeno, Tetsuo Ando, Yoshiyuki Morishita
Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient...
2018: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/29669381/prevalence-of-congenital-cmv-infection-and-antiviral-therapy-in-very-low-birth-weight-infants-observations-of-the-german-neonatal-network
#3
Alexander Humberg, Viola Leienbach, Mats I Fortmann, Tanja K Rausch, Horst Buxmann, Andreas Müller, Egbert Herting, Christoph Härtel, Wolfgang Göpel
BACKGROUND: To determine the prevalence of congenital CMV infection (cCMV) in very-low-birth-weight infants (VLBWI) and to evaluate epidemiological characteristics of VLBWI with antiviral therapy (AT). METHODS: CMV-specific PCR in umbilical cord tissue was performed (n=3330). Univariate analyses and logistic regression models were used to identify associations with outcome. RESULTS: 22/3330 VLBWI received AT (0.66%). 4 of these (0.12%) were PCR positive, with 2 VLBWI showing pathological screening for hearing loss...
April 18, 2018: Klinische Pädiatrie
https://www.readbyqxmd.com/read/29666167/a-flexible-mhc-class-i-multimer-loading-system-for-large-scale-detection-of-antigen-specific-t-cells
#4
Jolien J Luimstra, Malgorzata A Garstka, Marthe C J Roex, Anke Redeker, George M C Janssen, Peter A van Veelen, Ramon Arens, J H Frederik Falkenburg, Jacques Neefjes, Huib Ovaa
Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29663444/transitioning-cytomegalovirus-viral-load-testing-from-a-laboratory-developed-test-to-the-cobas%C3%A2-cmv-quantitative-nucleic-acid-assay
#5
Michael Payne, Linda Merrick, Tanya Lawson, Gordon Ritchie, Christopher Lowe
Commutability between human cytomegalovirus (CMV) viral load assays (VLA) is poor, despite the development of a WHO CMV International Standard (CMV IS). We evaluated a new CMV VLA, cobas® CMV, as compared to our current laboratory developed CMV VLA (LDT), for clinical use. Both the LDT and cobas® CMV were run in parallel for 109 patient samples. In addition, 104 replicates, over 8 dilutions, of the CMV IS were tested. Conversion factors and correlation between the two assays were calculated. The correlation coefficient between the LDT and cobas® CMV was 0...
April 16, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29663435/monitoring-of-oral-cytomegalovirus-dna-shedding-for-the-prediction-of-viral-dnaemia-in-allogeneic-hematopoietic-stem-cell-transplant-recipients
#6
Tania Pascual, Carlos Solano, Ignacio Torres, Alberto Talaya, Estela Giménez, Víctor Vinuesa, José Luis Piñana, Juan Carlos Hernández-Boluda, Ariadna Pérez, David Navarro
Preemptive antiviral therapy based on detecting cytomegalovirus (CMV) DNAemia above a preestablished threshold is the mainstay strategy for the prevention of CMV disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients; nevertheless, CMV DNAemia, even at low levels, may increase mortality. We investigated whether surveillance of saliva for the presence of CMV DNA may anticipate the occurrence of CMV DNAemia. This was a prospective observational study with 53 consecutively enrolled allo-HSCT recipients...
April 16, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29659179/nk-cell-and-th17-responses-are-differentially-induced-in-murine-cytomegalovirus-infected-renal-allografts-and-vary-according-to-recipient-virus-dose-and-strain
#7
Mao Li, Srinivasa Boddeda, Bo Chen, Qiang Zeng, Trenton R Schoeb, Victoria M Velazquez, Masako Shimamura
Human cytomegalovirus (HCMV) donor positive (D+) serostatus with acute rejection is associated with renal allograft loss, but the impact of recipient positive (R+) serostatus is unclear. In an allogeneic renal transplant model, antiviral natural killer (NK) and CD8+ T cell memory responses in murine CMV (MCMV) D+/R+ transplants were compared to D-/R- and D+/R- transplants, with recipient infection varied by MCMV dose and strain. D+/R- transplants had high primary antiviral cytolytic (interferon-γ+) and cytotoxic (granzyme B+) NK responses, whereas NK memory responses were lower in D+/R+ recipients receiving a high primary MCMV dose...
April 16, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29624457/low-seroprevalence-of-neutralizing-antibodies-targeting-two-clade-f-aav-in-humans
#8
Jeff L Ellsworth, Michael O'Callaghan, Hillard Rubin, Albert Seymour
To assess the therapeutic utility of AAVHSC15 and AAVHSC17, two recently described Clade F adeno-associated viruses (AAVs), the seroprevalence of neutralizing antibodies (NAbs) to these AAVs was assessed in a representative human population and compared to that of AAV9. NAb levels were measured in 100 unique human sera of different races (34, Black, 33 Caucasian, and 33 Hispanic) and sex (49% female, 51% male) collected within the United States. Fifty-six sera were tested in Huh7 cells and 44 sera were tested in 2V6...
March 2018: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29622669/secular-trends-in-infection-related-mortality-after-kidney-transplantation
#9
Susanna Kinnunen, Pauli Karhapää, Auni Juutilainen, Patrik Finne, Ilkka Helanterä
BACKGROUND AND OBJECTIVES: Infections are the most common noncardiovascular causes of death after kidney transplantation. We analyzed the current infection-related mortality among kidney transplant recipients in a nationwide cohort in Finland. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Altogether, 3249 adult recipients of a first kidney transplant from 1990 to 2012 were included. Infectious causes of death were analyzed, and the mortality rates for infections were compared between two eras (1990-1999 and 2000-2012)...
April 5, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29605039/activation-of-mammalian-target-of-rapamycin-induces-lipid-accumulation-in-the-diaphragm-of-ventilated-rats-and-hypoxia-treated-c2c12-cells
#10
Tao Yu, Mengli Wang, Yadong Wen, Yingya Cao, Guanggui Shen, Xiaogan Jiang, Jingyi Wu, Weihua Lu, Xiaoju Jin
BACKGROUND: Our previous study demonstrated that ventilators increase diaphragmatic lipid accumulation in rabbits, but their cellular mechanism is poorly understood. Mammalian target of rapamycin (mTOR) plays an important role in atherosclerosis in rat vascular smooth muscle cells. The present study investigated the role of mTOR pathway activation in the diaphragmatic muscle of ventilated rats and hypoxia-induced C2C12 cells. MATERIALS AND METHODS: Male Sprague-Dawly rats were randomized into a control group (n = 8), controlled mechanical ventilation (CMV) group (n = 8), and CMV + Rapa group (n = 8)...
May 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29602675/dna-sequence-specific-ligands-xvii-synthesis-spectral-properties-virological-and-biochemical-studies-of-fluorescent-dimeric-bisbenzimidazoles-dba-n
#11
Vasiliy S Koval, Albert F Arutyunyan, Victor L Salyanov, Regina R Klimova, Alla A Kushch, Ekaterina Yu Rybalkina, Olga Yu Susova, Alexei L Zhuze
A series of DNA minor groove binding fluorescent dimeric bisbenzimidazoles DBA(n) bearing linkers of various length were synthesized and their biochemical and antiviral activities were evaluated. Their antiviral activity was assessed in model cell systems infected with human herpes simplex virus (HSV-1) and cytomegalovirus (CMV). Compounds DBA(1) and DBA(7) demonstrated in vitro inhibitory properties towards HSV-1, and DBA(7) completely blocked the viral infection. Compound DBA(11) displayed the in vitro therapeutic activity towards both HSV-1 and CMV...
March 12, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29558877/incidence-and-risk-factors-for-leukopenia-in-kidney-transplant-recipients-receiving-valganciclovir-for-cytomegalovirus-prophylaxis
#12
Xinyun Liang, Olusegun Famure, Yanhong Li, S Joseph Kim
CONTEXT: Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. OBJECTIVE: To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. METHODS: In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis...
January 1, 2018: Progress in Transplantation
https://www.readbyqxmd.com/read/29554325/the-burden-of-congenital-cytomegalovirus-infection-a-prospective-cohort-study-of-20-000-infants-in-finland
#13
Laura Puhakka, Maija Lappalainen, Tuula Lönnqvist, Riina Niemensivu, Päivi Lindahl, Tea Nieminen, Raija Seuri, Irmeli Nupponen, Sunil Pati, Suresh Boppana, Harri Saxen
Background: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and causes significant morbidity. This study was undertaken to evaluate the benefits of screening newborns for cCMV and to understand the cCMV disease burden in Finland. Methods: Infants born in Helsinki area hospitals were screened for CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants and matched controls were monitored to determine their neurodevelopmental, audiological, and ophthalmological outcomes at 18 months of age...
March 15, 2018: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/29543540/immunopathology-of-virus-induced-anterior-uveitis
#14
Jolanda D F De Groot-Mijnes, Anita S Y Chan, Soon-Phaik Chee, Georges M G M Verjans
Herpes simplex virus, varicella zoster virus, human cytomegalovirus, and rubella virus are the most common causes of virus-induced anterior uveitis. They can present in a variety of entities not only with typical but also overlapping clinical characteristics. These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response. The infections differ in that the herpes viruses cause an acute lytic infection and inflammation, whereas rubella virus is a chronic low-grade infection with slowly progressing immunopathological responses...
March 15, 2018: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/29535361/herpesviruses-possess-conserved-proteins-for-interaction-with-nedd4-family-ubiquitin-e3-ligases
#15
Tetsuo Koshizuka, Takahiro Kobayashi, Ken Ishioka, Tatsuo Suzutani
Nedd4 is a family of ubiquitin E3 ligases that regulate numerous cellular processes. In this report, we showed that alpha- and beta-herpesviruses have membrane proteins that regulate the function of the Nedd4 family members. Although the homology search score was quite low, UL56 of herpes simplex virus type 1 and 2, ORF0 of varicella-zoster virus, UL42 of human cytomegalovirus, and U24 of human herpesvirus 6A, 6B, and 7 all possess at least one PPxY (PY) motif in their cytoplasmic domain, and are able to bind with Itch, a member of the Nedd4 family...
March 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29532684/routine-hematoxylin-and-eosin-stain-is-specific-for-the-diagnosis-of-cytomegalovirus-infection-in-gastrointestinal-biopsy-specimens
#16
Ling Guo, Tom C DeRoche, Ziyan T Salih, Shadi A Qasem
BACKGROUND: Gastrointestinal cytomegalovirus (CMV) infection is a serious complication in immunocompromised patients; clinicians often expect expedited results for biopsy specimens. Our goal is to determine the accuracy of identification of CMV on hematoxylin and eosin (H&E) stain. METHODS AND RESULTS: A total of 361 biopsy specimens from 273 patients with suspicion for CMV infection were retrieved. CMV was detected by immunohistochemistry (IHC) in 37 specimens acquired from 33 individual patients (average age = 54 years)...
March 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29532473/derivation-of-the-clonal-cell-lines-from-siberian-sturgeon-acipenser-baerii-head-kidney-cell-lines-and-its-applicability-to-foreign-gene-expression-and-virus-culture
#17
J H Ryu, M S Kim, J H Kang, D H Kim, Y K Nam, S P Gong
This study was conducted to establish and characterize the clonal-cell lines from Siberian sturgeon Acipenser baerii head-kidney tissues and to evaluate its applicability as a research tool. From the culture of A. baerii head-kidney derived cells, 10 cell lines were established first and then eight clonal-cell lines were derived from clonal growth and colony expansion of two cell lines that showed significant high colony-forming ability. All eight clonal-cell lines were morphologically similar and grew stably under monolayer culture but their growth rates were significantly different...
March 12, 2018: Journal of Fish Biology
https://www.readbyqxmd.com/read/29529309/relationship-between-t-cell-responses-to-cmv-markers-of-inflammation-and-frailty-in-hiv-uninfected-and-hiv-infected-men-in-the-multicenter-aids-cohort-study
#18
Joseph B Margolick, Jay H Bream, Tricia L Nilles, Huifen Li, Susan J Langan, Shane Deng, Ruibin Wang, Nikolas Wada, Sean X Leng
Background: Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown. Methods: T cells from men who have sex with men (22 virologically suppressed HIV+, 20 HIV-) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed...
February 26, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29528545/low-cytomegalovirus-seroprevalence-in-early-multiple-sclerosis-a-case-for-the-hygiene-hypothesis
#19
Elisenda Alari-Pahissa, Antía Moreira, Ana Zabalza, Roberto Alvarez-Lafuente, Elvira Munteis, Andrea Vera, Rafael Arroyo, Jose C Alvarez-Cermeño, Luisa Maria Villar, Miguel López-Botet, Jose E Martínez-Rodríguez
BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has been recently associated with a lower multiple sclerosis (MS) susceptibility, remaining controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in early MS as compared to non-early MS patients, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses...
March 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29518863/-clinical-study-of-low-cytomegalovirus-viral-load-thresholds-for-preemptive-antiviral-therapy-in-hematopoietic-cell-transplant-recipients
#20
L Li, Y Wang, C H Yan, X J Huang
Objective: To investigate the threshold of cytomegalovirus (CMV) DNAemia for preemptive antiviral therapy in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Viral load between 1×10(3) copies/ml and 5×10(3) copies/ml was defined as low viral load by real time Q-PCR. Clinical data and outcome were collected. Results: A total of 95 allo-HSCT recipients with low viral load from September 2014 to February 2015 were recruited in this study. The control group included 37 patients who received preemptive initial antiviral therapy...
March 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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