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Rizwan Ali, Sivaramakrishnan Ramadurai, Frank Barry, Heinz Peter Nasheuer
The modulation of expression levels of fluorescent fusion proteins (FFPs) is central for recombinant DNA technologies in modern biology as overexpression of proteins contributes to artifacts in biological experiments. In addition, some microscopy techniques such as fluorescence correlation spectroscopy (FCS) and single-molecule-based techniques are very sensitive to high expression levels of FFPs. To reduce the levels of recombinant protein expression in comparison with the commonly used, very strong CMV promoter, the herpes simplex virus thymidine kinase (TK) gene promoter, and mutants thereof were analyzed...
June 2018: FEBS Open Bio
Hung Cao Dinh, Ivan Bautmans, Ingo Beyer, Tony Mets, Oscar Okwudiri Onyema, Louis Nuvagah Forti, Wim Renmans, Sam Vander Meeren, Kristin Jochmans, Sofie Vermeiren, Roberta Vella Azzopardi, Rose Njemini
Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immuno-senescence (IS) - predominantly driven by cytomegalovirus (CMV) - has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty...
June 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Ana Laura Tellechea, Victoria Luppo, María Alejandra Morales, Boris Groisman, Agustin Baricalla, Cintia Fabbri, Anabel Sinchi, Alicia Alonso, Cecilia Gonzalez, Bibiana Ledesma, Patricia Masi, María Silva, Adriana Israilev, Marcela Rocha, Marcela Quaglia, María Paz Bidondo, Rosa Liascovich, Pablo Barbero
BACKGROUND: Zika virus (ZIKV) vertical transmission may lead to microcephaly and other congenital anomalies. In March and April 2016, the first outbreak of ZIKV occurred in Argentina. The objective was to describe the surveillance of newborns with microcephaly and other selected brain anomalies in Argentina, and evaluation different etiologies. METHODS: Participants were enrolled between April 2016 and March 2017. CASES: newborns from the National Network of Congenital Abnormalities of Argentina (RENAC) with head circumference lower than the 3rd percentile according to gestational age and sex, or selected brain anomalies...
June 19, 2018: Birth Defects Research
Fengjuan Liu, Jinji Liu, Zaimei Yuan, Yubo Qing, Honghui Li, Kaixiang Xu, Wanyun Zhu, Heng Zhao, Baoyu Jia, Weirong Pan, Jianxiong Guo, Xuezeng Zhang, Wenmin Cheng, Wei Wang, Hong-Ye Zhao, Hong-Jiang Wei
Pig-to-human organ transplantation has drawn attention in recent years due to the potential use of pigs as an alternative source of human donor organs. While GGTA1 knockout (GTKO) can protect xenografts from hyperacute rejection, complement-dependent cytotoxicity might still contribute to this type of rejection. To prolong the xenograft survival, we utilized a T2A-mediated pCMV-hCD55-T2A-hCD59-Neo vector and transfected the plasmid into GTKO Diannan miniature pig fetal fibroblasts. After G418 selection combined with single-cell cloning culture, four colonies were obtained, and three of these were successfully transfected with the hCD55 and hCD59...
June 18, 2018: Molecular Biotechnology
Zahava C Farkas, Lavneet Chawla, Shalom Frager, Edward Esses, Yasmin Yusuf, Brad Dworkin
Cytomegalovirus (CMV)-induced pseudotumors, or mass-like lesions in the colon, are a rare entity. We report a case of CMV-related spindle cell pseudotumor in an immunocompetent patient with a left ventricular assist device. This case highlights the importance of considering CMV-induced inflammatory pseudotumor when evaluating tumorous lesions in the colon, as well as the importance of appropriate diagnostic work-up, including proper biopsy technique and meticulous review of the pathology.
2018: ACG Case Reports Journal
Anum Asif, Maria Del Pilar Morales
The possible role of infectious and inflammatory states in the pathogenesis of atherosclerotic disease has been a matter of debate in the literature. There are case reports of active cytomegalovirus (CMV) infection unmasking underlying dormant systemic lupus erythematosus (SLE). CMV infection has also been postulated to be associated with atherosclerosis development in the coronaries. We present a unique case where a patient with newly diagnosed SLE and acute myocardial infarction was found to have high anti-CMV titers suggesting concomitant active CMV infection...
2018: Journal of Community Hospital Internal Medicine Perspectives
Sunwen Chou, L Elizabeth Satterwhite, Ronald J Ercolani
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor recently approved as prophylaxis in stem cell transplant recipients. In further studies of emerging drug resistance, a baseline laboratory CMV strain was serially propagated in cell culture under a combination of letermovir and ganciclovir. In 8 experiments, UL56 terminase gene mutations were detected beginning at 10 passages, including novel amino acid substitutions V236A, L328V and A365S, in a region previously associated with letermovir resistance...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Young C Shin, Georg F Bischof, William A Lauer, Lucas Gonzalez-Nieto, Eva G Rakasz, Gregory M Hendricks, David I Watkins, Mauricio A Martins, Ronald C Desrosiers
The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme...
June 18, 2018: PLoS Pathogens
Munmi Borah, Margarita Berbati, Chrysavgi Reppa, Maria Holeva, Palash Deb Nath, Andreas Voloudakis
Cucumber mosaic virus (CMV) causes great losses in Bhut Jolokia pepper ( Capsicum chinense Jacq.) plantations in Assam, India. To investigate possible means to induce plant resistance against this virus, the crude extract of bacterially-expressed double-stranded (ds) RNA, derived from CMV-2b gene (dsRNA_CMV-2b), was exogenously applied along with CMV-G strain onto Bhut Jolokia plants. In this 'RNA-vaccination' bioassay, disease incidence, assessed by testing the plants at 21 days post inoculation by DAS-ELISA, ranged from 0 to 29% in case of dsRNA-treated plants, and from 55 to 92% when only CMV was applied...
June 2018: Virusdisease
Amanda Soares Alves, Mayari Eika Ishimura, Yeda Aparecida de Oliveira Duarte, Valquiria Bueno
Aim: The increased number of individuals older than 80 years, centenarians, and supercentenarians is not a synonym for healthy aging, since severe infections, hospitalization, and disability are frequently observed. In this context, a possible strategy is to preserve the main characteristics/functions of the immune system with the aim to cause less damage to the organism during the aging process. Vitamin D acts on bone marrow, brain, breast, malignant cells, and immune system and has been recommended as a supplement...
2018: Frontiers in Immunology
Nicolas De Neuter, Esther Bartholomeus, George Elias, Nina Keersmaekers, Arvid Suls, Hilde Jansens, Evelien Smits, Niel Hens, Philippe Beutels, Pierre Van Damme, Geert Mortier, Viggo Van Tendeloo, Kris Laukens, Pieter Meysman, Benson Ogunjimi
Pathogens of past and current infections have been identified directly by means of PCR or indirectly by measuring a specific immune response (e.g., antibody titration). Using a novel approach, Emerson and colleagues showed that the cytomegalovirus serostatus can also be accurately determined by using a T cell receptor repertoire data mining approach. In this study, we have sequenced the CD4+ memory T cell receptor repertoire of a Belgian cohort with known cytomegalovirus serostatus. A random forest classifier was trained on the CMV specific T cell receptor repertoire signature and used to classify individuals in the Belgian cohort...
June 15, 2018: Genes and Immunity
Ying-Hong Wang, Dapeng Chen, Georgy Hartmann, Carolyn R Cho, Karsten Menzel
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor for the prophylaxis of CMV infection in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. In vitro, letermovir is a time-dependent inhibitor and an inducer of cytochrome P450 (CYP)3A, and an inhibitor of CYP2C8 and organic anion transporting polypeptide (OATP)1B. A stepwise approach was taken to qualify the interaction model of an existing letermovir physiologically-based pharmacokinetic (PBPK) model to predict letermovir interactions with CYP3A and OATP1B...
June 14, 2018: Clinical Pharmacology and Therapeutics
R J Arasaratnam, I Tzannou, T Gray, P I Aguayo-Hiraldo, M Kuvalekar, S Naik, A Gaikwad, H Liu, T Miloh, J F Vera, R W Himes, F M Munoz, A M Leen
Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between post-transplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year post-transplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered post-transplant, coincident with the introduction and subsequent routine tapering of immunosuppression...
June 13, 2018: American Journal of Transplantation
Claire Aguilar, Shahid Husain, Olivier Lortholary
Background: Undergoing solid organ transplantation (SOT) exposes the recipient to various infectious risks, including possible transmission of pathogen by the transplanted organ, post-surgical infections, reactivation of latent pathogens, or novel infections. Recent advances: In the last few years, the emergence of Zika virus has raised concerns in the transplant community. Few cases have been described in SOT patients, and these were associated mainly with moderate disease and favorable outcome; the notable exception is a recent case of fatal meningo-encephalopathy in a heart transplant recipient...
2018: F1000Research
Cian M McCrudden, John W McBride, Joanne McCaffrey, Emma M McErlean, Nicholas J Dunne, Vicky L Kett, Jonathan A Coulter, Tracy Robson, Helen O McCarthy
Background: Recent approvals of gene therapies by the FDA and the EMA for treatment of inherited disorders have further opened the door for assessment of nucleic acid pharmaceuticals for clinical usage. Arising from the presence of damaged or inappropriate DNA, cancer is a condition particularly suitable for genetic intervention. The RALA peptide has been shown to be a potent non-viral delivery platform for nucleic acids. This study examines the use of RALA to deliver a plasmid encoding inducible nitric oxide synthase (iNOS) as an anti-cancer treatment...
2018: Cancer Nanotechnology
Carlos Solano, Estela Giménez, Eliseo Albert, Eva María Mateo, Montserrat Gómez, Rosa Goterris, Ariadna Pérez, Paula Amat, Juan Carlos Hernández-Boluda, Marc Poch, José Luis Piñana, David Navarro
To gauge the risk of delaying initiation of prophylaxis with letermovir from the time of donor infusion to prevent CMV infection in allo-HSCT recipients we investigated the clinical outcomes of CMV DNAemia episodes occurring before engraftment, and compared to that of episodes developing after engraftment (up to day +365). A total of 197 consecutive adult patients were included. Plasma CMV DNA load was monitored by real-time PCR assays [limit of detection: 31 IU/ml]. A total of 150 out of 197 patients had CMV DNAemia (cumulative incidence of 77%; 95% CI, 73-81%), and 38 out of the 197 patients developed it before engraftment (cumulative incidence, 19%; 95% CI, 10-30...
June 13, 2018: Bone Marrow Transplantation
Janet Lei, Egon J Jacobus, William K Taverner, Kerry D Fisher, Silvio Hemmi, Katy West, Lorna Slater, Fred Lilley, Alice Brown, Brian Champion, Margaret R Duffy, Len W Seymour
BACKGROUND: Oncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential...
June 13, 2018: Journal for Immunotherapy of Cancer
Naoki Inoue, Mao Abe, Ryo Kobayashi, Souichi Yamada
The development of a cytomegalovirus (CMV) vaccine has become a top priority due to its potential cost-effectiveness and associated public health benefits. However, there are a number of challenges facing vaccine development including the following: (1) CMV has many mechanisms for evading immune responses , and natural immunity is not perfect, (2) the immune correlates for protection are unclear, (3) a narrow range of CMV hosts limits the value of animal models, and (4) the placenta is a specialized organ formed transiently and its immunological status changes with time...
2018: Advances in Experimental Medicine and Biology
Tetsushi Yoshikawa
Two of the four betaherpesviruses, Cytomegalovirus (CMV) and human herpesvirus 6B (HHV-6B), play an important role in opportunistic infections in hematopoietic stem cell transplant (HSCT) recipients. These viruses are ubiquitous in humans and can latently infect mononuclear lymphocytes, complicating the diagnosis of the diseases they cause. Although the detection of viral DNA in a patient's peripheral blood by real-time PCR is widely used for monitoring viral infection, it is insufficient for the diagnosis of virus-associated disease...
2018: Advances in Experimental Medicine and Biology
Alfonso J Rodriguez-Morales, Jaime A Cardona-Ospina, Valeria Ramirez-Jaramillo, Javier A Gaviria, Gloria María González-Moreno, Juan D Castrillón-Spitia, Alejandra López-Villegas, Estefania Morales-Jiménez, Valentina Ramírez-Zapata, German Eduardo Rueda-Merchán, Adriana M Trujillo, Fredy A Tabares-Villa, Valentina Henao-SanMartin, David R Murillo-Garcia, Johana Andrea Herrera-Soto, Marta Liliana Buitrago-Cañas, Matthew H Collins, Juan Carlos Sepúlveda-Arias, José J Londoño, Héctor D Bedoya-Rendón, Javier de Jesús Cárdenas-Pérez, Sandra X Olaya, Guillermo J Lagos-Grisales
BACKGROUND: Zika virus (ZIKV) infection has emerged as a significant threat for pregnant women and newborns in populations living in or visiting Latin America. We previously reported a preliminary analysis in Sucre, Colombia, as the first group of pregnant women with RT-PCR-confirmed ZIKV (ZIKa enEmbarazadas yReciénNacidos enCOLombia, ZIKERNCOL). METHODS: In this second report, findings of the first 86 pregnant women from La Virginia and Dosquebradas (municipalities), Risaralda, Colombia, with RT-PCR-confirmed ZIKV infection are reported...
June 9, 2018: Travel Medicine and Infectious Disease
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