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Matthew J Murray, Nicholas E Peters, Matthew B Reeves
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection-where the virus establishes an infection in an absence of many gene products specific for lytic infection-these initial interactions are crucial events...
March 16, 2018: Pathogens
Koh-Hei Yamada, Ryuichi Majima, Toyofumi Yamaguchi, Naoki Inoue
Background Previously, we established a reporter cell line for human cytomegalovirus and screened anti-human cytomegalovirus compounds using the cell line. In this study, we characterized one of the identified compounds, 2,4-diamino-6-(4-methoxyphenyl)pyrimidine (coded as 35C10). Methods 50% Effective concentrations (EC50s) and 50% cytotoxic concentrations (CC50s) of 35C10 and its derivatives in human fibroblasts were determined by X-gal staining of the cells infected with human cytomegalovirus Towne strain expressing β-galactosidase...
January 2018: Antiviral Chemistry & Chemotherapy
Thomas Tängdén, Pier Giorgio Cojutti, Jason A Roberts, Federico Pea
BACKGROUND AND OBJECTIVES: Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations. METHODS: Therapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively...
March 15, 2018: Clinical Pharmacokinetics
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
Tiziana Lazzarotto, Angela Chiereghin, Antonio Piralla, Giulia Piccirilli, Alessia Girello, Giulia Campanini, Liliana Gabrielli, Cristina Costa, Arcangelo Prete, Francesca Bonifazi, Alessandro Busca, Roberto Cairoli, Anna Amelia Colombo, Marco Zecca, Francesca Sidoti, Gabriele Bianco, Pierpaolo Paba, Carlo Federico Perno, Rossana Cavallo, Fausto Baldanti
Currently, no consensus has been reached on the optimal blood compartment to be used for surveillance of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia. Although several comparative studies have been performed correlating CMV and EBV DNA loads in whole blood (WB) vs plasma, to our knowledge, no studies have ever analyzed the kinetics of both viruses in the two blood compartments. In this retrospective non-interventional multicenter cohort study the kinetics of CMV and EBV DNA in 121 hematopoietic stem cell transplant recipients (HSCTR) have been investigated by analyzing in parallel 569 and 351 paired samples from 80 and 58 sequential episodes of CMV and EBV DNAemia, respectively...
March 12, 2018: Biology of Blood and Marrow Transplantation
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
Eun Ae Kang, Hyuk Yoon, A Young Seo, Cheol Min Shin, Jong Pil Im, Young Soo Park, Joo Sung Kim, Nayoung Kim, Dong Ho Lee
OBJECTIVES: Cytomegalovirus (CMV) disease is more common in immunocompromised patients but may occur in people with normal immune function. In addition, CMV enterocolitis can aggravate inflammatory bowel diseases (IBD), but there was little knowledge of differences in clinical and endoscopic features of CMV enterocolitis between patients with IBD and without IBD. The aim of this study was to determine the difference in clinical implication in CMV enterocolitis between the IBD patients and non-IBD patients...
March 15, 2018: Scandinavian Journal of Gastroenterology
Michelle K Yong, Sharon R Lewin, Oriol Manuel
PURPOSE OF REVIEW: Immune monitoring to determine when and how the recovery of cytomegalovirus (CMV)-specific T-cells occurs post-transplantation may help clinicians to risk stratify individuals at risk of complications from CMV. We aimed to review all recent clinical studies using CMV immune monitoring in the pre- and post-transplant setting including the use of recently developed standardized assays (Quantiferon-CMV and the CMV ELISPOT) to better understand in whom, when, and how immune monitoring is best used...
March 14, 2018: Current Infectious Disease Reports
Xingxing Yu, Lingling Xu, Yingjun Chang, Xiaojun Huang, Xiangyu Zhao
The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Th1, Th2, Th3 and Tr1 cells. Here, we investigate levels of type 1 (IFN-gamma; NK1), type 2 (IL-13; NK2), type 3 (TGF-beta; NK3) and regulatory (IL-10; NKr) cytokines in peripheral blood to assess the cytokine profiles of natural killer (NK) cells following human allogeneic hematopoietic stem cell transplantation (allo-HSCT). NK2 and NK3 cell expansion was observed after allo-HSCT; levels of NKr cells reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT...
March 9, 2018: Science China. Life Sciences
Steffi De Pelsmaeker, Nicolas Romero, Massimo Vitale, Herman W Favoreel
Natural killer (NK) cells play an important role in the host response against viral infections and cancer development. They are able to kill virus-infected and tumor cells, and produce different important cytokines that stimulate the antiviral and antitumor adaptive immune response, particularly interferon gamma. NK cells are of particular importance in herpesvirus infections, which is illustrated by systemic and life-threatening herpesvirus disease symptoms in patients with deficiencies in NK cell activity, and by the myriad of reports describing herpesvirus NK cell evasion strategies...
March 14, 2018: Journal of Virology
Karen Hasselmo, Matthias R Mehl, Allison M Tackman, Angela L Carey, Anne M Wertheimer, Raymond P Stowe, David A Sbarra
Background: Close relationships play an integral role in human development, and robust evidence links marital separation and divorce to poor health outcomes. Social integration may play a key role in this association. In many ways, the study of marital separation and divorce provides an ideal model system for a more complete understanding of the association between life stress and physical health. Purpose: The current study investigated associations among objectively measured social integration, psychological distress, and biomarkers of immune health in recently separated adults (N = 49)...
February 5, 2018: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
Lola Madrid, Rosauro Varo, Sonia Maculuve, Tacilta Nhampossa, Carmen Muñoz-Almagro, Enrique J Calderón, Cristina Esteva, Carla Carrilho, Mamudo Ismail, Begoña Vieites, Vicente Friaza, María Del Carmen Lozano-Dominguez, Clara Menéndez, Quique Bassat
BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity...
2018: PloS One
Clive M Michelo, Bram van Cranenbroek, Peran Touw, Frans H J Claas, Arnold van der Meer, Irma Joosten
Background: Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity. Methods: We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells...
December 2017: Transplantation Direct
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
Miri Shnayder, Aharon Nachshon, Benjamin Krishna, Emma Poole, Alina Boshkov, Amit Binyamin, Itay Maza, John Sinclair, Michal Schwartz, Noam Stern-Ginossar
Primary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, with one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive transcriptome RNA sequencing (RNA-seq) atlas generated by the Genotype-Tissue Expression (GTEx) project...
March 13, 2018: MBio
Rajesh Kumar Wadhwa, Aisha Nazeer, Ayesha Aslam Rai, Nasir Hassan Luck
OBJECTIVES: We investigated the incidence of gastrointestinal disorders requiring endoscopic and histopathologic diagnoses in renal transplant recipients. MATERIALS AND METHODS: In this retrospective analysis, we examined records of patients seen at the Department of Hepato-Gastroenterology and Transplantation Sciences, Sindh Institute of Urology and Trans?lantation (Karachi, Pakistan) from January 2010 to December 2014. Renal transplant recipients with gastrointestinal disorders who required endoscopy, including proctoscopy and upper and lower gastrointestinal endoscopy as per indication, were included...
March 9, 2018: Experimental and Clinical Transplantation
Karl-Heinz Deeg
Prenatal, neonatal meningoencephalitis and infections of the brain in older infants are often associated with serious complications which can be diagnosed by sonography through the open fontanelles. Most frequently postmeningitic hydrocephalus and subdural effusions occur. Rarer complications are brain abscesses and ventriculitis which are caused by gram negative bacteria such as E. coli, Serratia marcescens, Proteus and Enterobacter. A serious complication after ventriculitis is the development of compartment hydrocephalus...
March 13, 2018: Ultraschall in der Medizin
Jane Cho, Nicole Siegel, Manju L Subramanian, Howard Ying, Steven Ness
PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis...
March 12, 2018: Retinal Cases & Brief Reports
Mikhail V Pogorelyy, Anastasia A Minervina, Dmitriy M Chudakov, Ilgar Z Mamedov, Yuri B Lebedev, Thierry Mora, Aleksandra M Walczak
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associating receptors to disease from only a small cohort of patients, with no need for a control cohort. Our method successfully identifies previously validated Cytomegalovirus and type 1 diabetes responsive TCR β sequences...
March 13, 2018: ELife
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
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