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Tobias Cohen, Toni M Schwarz, Frederic Vigant, Thomas J Gardner, Rosmel E Hernandez, Benhur Lee, Domenico Tortorella
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface...
October 24, 2016: Viruses
Jennifer A Slyker
Cytomegalovirus (CMV) was among the most common AIDS-defining illnesses prior to the advent of combination antiretroviral therapy (ART). In the ART era, CMV disease remains a significant public health threat among HIV-infected adults and children with delayed HIV diagnosis. CMV co-infection may additionally contribute to accelerated HIV progression, development of inflammation-related comorbidities, immune senescence and developmental deficits. Elimination of CMV would have tremendous public health significance and is an important priority; however, current vaccine strategies are not targeted at HIV-infected individuals...
October 5, 2016: Journal of Virus Eradication
Mark R Schleiss
Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although such associations remain controversial...
October 5, 2016: Journal of Virus Eradication
Kathryn S Carpentier, Nicolle M Esparo, Stephanie J Child, Adam P Geballe
During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1...
October 2016: PLoS Pathogens
Adrian Guthals, Yutian Gan, Laura Murray, Yongmei Chen, Jeremy Stinson, Gerald R Nakamura, Jennie R Lill, Wendy Sandoval, Nuno Bandeira
One direct route for the discovery of therapeutic human monoclonal antibodies (mAbs) involves the isolation of peripheral B cells from survivors/sero-positive individuals after exposure to an infectious reagent or disease etiology followed by single-cell sequencing or hybridoma generation. Peripheral B cells, however, are not always easy to obtain and only represent a small percentage of the total B cell population across all bodily tissues. Although it has been demonstrated that tandem mass spectrometry (MS/MS) techniques can interrogate the expressed polyclonal antibody (pAb) response to an antigen in vivo, all current approaches identify MS/MS spectra against databases derived from genetic sequencing of B cells from the same patient...
October 25, 2016: Journal of Proteome Research
Da Hae Lee, Bart Keymeulen, Robert Hilbrands, Zhidong Ling, Ursule Van de Velde, Daniel Jacobs-Tulleneers-Thevissen, Geert Maleux, Bruno Lapauw, Laurent Crenier, Christophe De Block, Chantal Mathieu, Daniel Pipeleers, Pieter Gillard
BACKGROUND: Induction therapy with a T cell depleting agent followed by mycophenolate mofetil (MMF) and tacrolimus (Tac) is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. METHODS: Fifty-one patients (ages between 29-63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin (ATG)-MMF-Tac protocol...
October 25, 2016: Transplantation
Antonella Vitti, Elisa Pellegrini, Cristina Nali, Stella Lovelli, Adriano Sofo, Maria Valerio, Antonio Scopa, Maria Nuzzaci
Understanding the induction of plant defenses against viruses using biocontrol agents is essential for developing new strategies against these pathogens, given the ineffectiveness of chemical treatments. The ability of Trichoderma harzianum, strain T-22 (T22) to control Cucumber mosaic virus (CMV) in Solanum lycopersicum var. cerasiforme plants and the changes in the physiology of tomato treated/infected with T22/CMV were examined. Plant growth-promoting effects, photosynthetic performance, reactive oxygen species scavenging enzymes, and phytohormones were investigated...
2016: Frontiers in Plant Science
Gabriel P Joseph, Ryan McDermott, Maria A Baryshnikova, Charles S Cobbs, Ilya V Ulasov
Glioblastoma multiforme (GBM) is the most aggressive neoplastic brain tumor in humans with a median survival of less than 2 years. It is therefore critical to understand the mechanism of glioma progression and to identify future targets for intervention. We investigate the mechanisms of cytomegalovirus as an oncomodulatory agent implicated in glioma progression, as well as immunosuppression. This review provides a comprehensive evaluation of recent investigative developments concerning the role of CMV in cellular processes during glioma growth...
October 21, 2016: Cancer Letters
Sanjay K Agarwal, Dipankar Bhowmik, Sandeep Mahajan, Soumita Bagchi
INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipient (RTR). Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. METHODS: In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded...
October 24, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamas Fulop, Janet E McElhaney, Melissa K Andrew, Stephen D Walter, P J Devereaux, Mehrnoush Malek, Ryan R Brinkman, Jonathan Bramson, Mark Loeb
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female)...
October 24, 2016: Journal of the American Geriatrics Society
Parikshaa Gupta, Dipanjan Haldar, Jasmine Naru, Pranab Dey, Ashutosh Nath Aggarwal, Ranjana Walker Minz, Ritu Aggarwal
BACKGROUND: Oncogenic viruses have recently been allied with lung carcinoma, however, the causal association has not been established till date. The study was conducted to determine the prevalence of high-risk Human papillomavirus (HPV; subtypes 16, 18, 31, 33 and 45), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in lung carcinoma using polymerase chain reaction (PCR) on fine needle aspirates. METHODS: Fine needle aspirates of patients with lung carcinoma were included as cases...
October 24, 2016: Diagnostic Cytopathology
Athanasios Tsiouris, Lynn Wilson, Rajesh B Sekar, Abeel A Mangi, James J Yun
BACKGROUND: A lack of donor hearts remains a major limitation of heart transplantation. Hearts from Centers for Disease Control (CDC) high-risk donors can be utilized with specific recipient consent. However, outcomes of heart transplantation with CDC high-risk donors are not well known. We sought to define outcomes, including posttransplant hepatitis and human immunodeficiency virus (HIV) status, in recipients of CDC high-risk donor hearts at our institution. METHODS: All heart transplant recipients from August 2010 to December 2014 (n = 74) were reviewed...
October 23, 2016: Journal of Cardiac Surgery
Todd A Fehniger, Megan A Cooper
Due to their ability to kill cancer cells and produce proinflammatory cytokines, natural killer (NK) cells have long been of clinical interest for their antitumor properties. The recent discovery of NK cell memory demonstrates that NK cell functions, and potentially antitumor responses, can be enhanced long term. Following nonspecific activation with the cytokines IL-12, IL-15, and IL-18 or in response to antigens or cytomegalovirus (CMV), human and mouse NK cells exhibit stable, enhanced functional responses with phenotypic and molecular changes...
October 20, 2016: Trends in Immunology
Carlos A Q Santos
Cytomegalovirus (CMV), human herpes virus (HHV)-6, and HHV-7 are ubiquitous β-herpesviruses that can cause opportunistic infection and disease in kidney transplant recipients. Active CMV infection and disease are associated with acute allograft failure and death, and HHV-6 and HHV-7 replication are associated with CMV disease. CMV prevention strategies are used commonly after kidney transplantation, and include prophylaxis with antiviral medications and preemptive treatment upon the detection of asymptomatic viral replication in blood...
September 2016: Seminars in Nephrology
Yeshwondm Mamuye, Balkachew Nigatu, Delayehu Bekele, Mekonen Getahun
BACKGROUND: Maternal cytomegalovirus (CMV) and Rubella infections result in adverse neonatal outcomes. Both CMV and Rubella are more widespread in developing countries and in communities with lower socioeconomic status. Thus, the aim of this study was to determine IgM specific to CMV and Rubella among newborns and Maternal CMV-seroprevalence and to identify risk factors. METHOD AND FINDING: Using cross sectional study design a total of 312 (156 newborns and 156 mothers) study participants were recruited by simple random sampling technique from gynecology outpatient department (OPD) and ward, starting from April 1, 2015 to June 30, 2015...
October 21, 2016: BMC Research Notes
Xiaohong Liu, Jinmei Xu, Hua Zhang, Qin Liu, Jingfan Xiao, Yuanxing Zhang
Edwardsiella tarda is associated with edwardsiellosis in cultured fish, resulting in heavy losses in aquaculture. So far, different types of vaccine have been attempted against E. tarda. In this study, an optimized eukaryotic expression plasmid was developed and an optimized DNA vaccine co-encoding antigenic and adjuvant peptide using a bicistronic expression system was designed. As a result, a modified plasmid harbored cytomegalovirus (CMV) promoter attached with R region of long terminal repeat from human T-cell leukemia virus type 1 (CMV/R) and woodchuck hepatitis virus post-transcriptional response element (WPRE) component showed an increased antigenic gene expression compared with unmodified plasmid...
October 17, 2016: Fish & Shellfish Immunology
Lauren Beswick, Bei Ye, Daniel R van Langenberg
INTRODUCTION: Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS: A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented...
October 18, 2016: Inflammatory Bowel Diseases
Masayoshi Okumi, Yasuyuki Sato, Kohei Unagami, Toshihito Hirai, Hideki Ishida, Kazunari Tanabe
BACKGROUND: The reasons for improved outcomes associated with preemptive kidney transplantation (PKT) are incompletely understood, and post-transplant complications have been scarcely investigated. METHODS: We evaluated the outcomes of PKT in both unmatched (n = 1060) and propensity score matched cohorts (n = 186) of adults who underwent living kidney transplant between 2000 and 2014. Outcomes were estimated glomerular filtration rate (eGFR), biopsy-proven rejection, cytomegalovirus (CMV) infection, post-transplant diabetes mellitus (PTDM), cardiovascular disease (CVD), graft failure (non-censored for death), and malignancy...
October 19, 2016: Clinical and Experimental Nephrology
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
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