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https://www.readbyqxmd.com/read/28100301/high-throughput-screening-of-a-glaxosmithkline-protein-kinase-inhibitor-set-identifies-an-inhibitor-of-human-cytomegalovirus-replication-that-prevents-creb-and-histone-h3-post-translational-modification
#1
Amina S Khan, Matthew J Murray, Catherine M K Ho, William J Zuercher, Matthew B Reeves, Blair L Strang
To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high throughput strategy to screen a GlaxoSmithKline (GSK) Published Kinase Inhibitor Set (PKIS). This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen we identified compounds within chemotypes that impede HCMV replication and identified kinase proteins associated with inhibition of HCMV replication that are potential novel anti-HCMV targets...
January 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#2
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28095374/human-cytomegalovirus-infection-in-nonimmunocompromised-patients-a-retrospective-analysis-and-review-of-the-literature
#3
Konstantin Zedtwitz-Liebenstein, Magda Diab-Elschahaw, Michael Frass
In a retrospective analysis of patients visiting the Outpatient Department of the Division of Infectious Diseases and Tropical Medicine over a period of 3 years, we found a high incidence of symptomatic nonsevere human cytomegalovirus (HCMV) infection in nonimmunocompromised patients. We present 11 symptomatic cases of HCMV infection in nonimmunocompromised patients with non-life-threatening symptoms like long-lasting depletion, fatigue, and subfebrile fever with or without muscular pain and arthralgia. Although the symptoms were not life-threatening, all of the patients suffered a prolonged duration of the disease until improvement...
January 18, 2017: Intervirology
https://www.readbyqxmd.com/read/28093266/comparative-analysis-of-nk-cell-receptor-repertoire-in-adults-and-very-elderly-subjects-with-cytomegalovirus-infection
#4
Guillermo Juárez-Vega, Velia Rangel-Ramírez, Adriana Monsiváis-Urenda, Perla Niño-Moreno, Christian Garcia-Sepúlveda, Daniel E Noyola, Roberto González-Amaro
Human cytomegalovirus (HCMV) infection in children and young adults has been associated with changes in the innate immune system. We herein analyzed the possible effect of very long term HCMV infection on the expression of several NK cell receptors. Ninety HCMV-seropositive individuals were included and classified as young adults (n=30), elderly (n=30) and very elderly subjects (n=30). A peripheral blood sample was obtained and the expression of NK cell receptors (NKG2A, NKG2C, ILT2, CD161, KIR2DL1, KIR3DL1, and KIR3DL2) by NK and other lymphocyte subsets was assessed by flow cytometry...
January 13, 2017: Human Immunology
https://www.readbyqxmd.com/read/28077654/neutralization-of-diverse-human-cytomegalovirus-strains-conferred-by-antibodies-targets-viral-gh-gl-pul128-131-pentameric-complex
#5
Sha Ha, Fengsheng Li, Matthew C Troutman, Daniel C Freed, Aimin Tang, John W Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C Nickle, Richard R Rustandi, Melissa Hamm, Pete A DePhillips, Ningyan Zhang, Jason S McLellan, Hua Zhu, Stuart P Adler, Michael A McVoy, Zhiqiang An, Tong-Ming Fu
: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex gH/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross neutralize the field strains of HCMV, remains a challenge...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077639/identification-of-a-continuous-neutralizing-epitope-within-ul128-of-human-cytomegalovirus
#6
Flavia Chiuppesi, Teodora Kaltcheva, Meng Zhuo, Peter A Barry, Don J Diamond, Felix Wussow
: As human cytomegalovirus (HCMV) is the most common infectious cause of fetal anomalies during pregnancy, developing a vaccine that prevents HCMV infection is considered a global health priority. Although HCMV immune correlates of protection are only poorly defined, neutralizing antibodies (NAb) targeting the envelope pentamer complex (PC) composed of subunits gH, gL, UL128, UL130, and UL131A are thought to contribute in preventing HCMV infection. Here, we describe a continuous target sequence within UL128 that is recognized by a previously isolated potent PC-specific NAb, termed 13B5...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28060895/a-luciferase-gene-driven-by-an-alphaherpesviral-promoter-also-responds-to-immediate-early-antigens-of-the-betaherpesvirus-hcmv-allowing-comparative-analyses-of-different-human-herpesviruses-in-one-reporter-cell-line
#7
Anna Katharina Maier, Raimund Jung, Clarissa Villinger, Axel Schubert, Paul Walther, Christian Sinzger, Diana Lieber
Widely used methods for quantification of human cytomegalovirus (HCMV) infection in cell culture such as immunoblotting or plaque reduction assays are generally restricted to low throughput and require time-consuming evaluation. Up to now, only few HCMV reporter cell lines have been generated to overcome these restrictions and they are afflicted with other limitations because permanently expandable cell lines are normally not fully permissive to HCMV. In this work, a previously existing epithelial cell line hosting a luciferase gene under control of a Varicella-zoster virus promoter was adopted to investigate HCMV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28055519/seroprevalence-of-cytomegalovirus-infection-among-a-rural-population-of-c%C3%A3-te-d-ivoire
#8
Augustin Etile Anoh, Arsène Mossoun, Chantal Akoua-Koffi, Emmanuel Couacy-Hymann, Maude Pauly, Siv-Aina Leendertz, Eliezer Kouakou N'goran, Grit Schubert, Sabrina Weiss, Jörg Hofmann, Fabian H Leendertz, Bernhard Ehlers
Human cytomegalovirus (HCMV) is a betaherpesvirus that can be pathogenic to humans. In particular, immunocompromised patients can develop life-threatening symptoms. In the present study, HCMV seroprevalence was investigated in a rural population of Western Côte d'Ivoire. Plasma samples collected from 166 apparently healthy subjects living in 8 villages surrounding the Taï Forest National Park were tested for anti-HCMV immunoglobulin G and M antibody with two commercial enzyme-linked immunosorbent assays. Prevalence of anti-HCMV IgG and IgM antibody was 100% and 5...
January 2017: Viral Immunology
https://www.readbyqxmd.com/read/28053099/hcmv-specific-cd4-t-cells-are-poly-functional-and-can-respond-to-hcmv-infected-dendritic-cells-in-vitro
#9
Sarah E Jackson, George X Sedikides, Gavin M Mason, Georgina Okecha, Mark R Wills
: Human cytomegalovirus (HCMV) infection and periodic re-activation is generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8+ T cell response to HCMV has been extensively studied, the HCMV-specific CD4+ T cell effector response is not as well understood, especially in the context of direct interactions with HCMV infected cells. We screened the IFNγ and IL-10 response to 6 HCMV peptide pools (selected as the most frequently responded to in our previous studies: pp65, pp71, IE1, IE2, gB and US3) in 84 donors, aged 23 - 74 years...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28051642/early-stage-of-cytomegalovirus-infection-suppresses-host-microrna-expression-regulation-in-human-fibroblasts
#10
Anton A Buzdin, Alina V Artcibasova, Natalya F Fedorova, Maria V Suntsova, Andrew V Garazha, Maxim I Sorokin, Daria Allina, Mikhail Shalatonin, Nikolay M Borisov, Alex A Zhavoronkov, Igor Kovalchuk, Olga Kovalchuk, Alla A Kushch
Responses to human cytomegalovirus (HCMV) infection are largely individual and cell type specific. We investigated molecular profiles in 2 primary cell cultures of human fibroblasts, which are highly or marginally sensitive to HCMV infection, respectively. We screened expression of genes and microRNAs (miRs) at the early (3 hours) stage of infection. To assess molecular pathway activation profiles, we applied bioinformatic algorithms OncoFinder and MiRImpact. In both cell types, pathway regulation properties at mRNA and miR levels were markedly different...
December 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/28046022/association-of-tlr3-l412f-polymorphism-with-cytomegalovirus-infection-in-children
#11
Mirosława Studzińska, Agnieszka Jabłońska, Małgorzata Wiśniewska-Ligier, Dorota Nowakowska, Zuzanna Gaj, Zbigniew J Leśnikowski, Teresa Woźniakowska-Gęsicka, Jan Wilczyński, Edyta Paradowska
Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection...
2017: PloS One
https://www.readbyqxmd.com/read/28035083/us28-a-virally-encoded-gpcr-as-an-antiviral-target-for-human-cytomegalovirus-infection
#12
REVIEW
Sungjin Lee, Yoon Hee Chung, Choongho Lee
Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the beststudied example of virally-encoded GPCRs to manipulate host GPCR signaling...
January 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28032284/baseline-antibody-level-may-help-predict-the-risk-of-active-human-cytomegalovirus-infection-in-a-hcmv-seropositive-population
#13
T-D Li, J-J Li, X Huang, H Wang, X-Y Guo, S-X Ge, J Zhang
Recurrent human cytomegalovirus (HCMV) infection during pregnancy could lead to congenital HCMV infection and permanent sequelae. However, knowledge regarding the risk factors associated with recurrent HCMV infection is limited. In the present study, 1,659 paired serum samples from the natural population were collected in Guangxi Province, China, from 2003 to 2004 with a 1-year interval. The serum anti-pp150 titre was quantitatively determined using a homemade recombinant pp150-based ELISA, and the IgG titre that increased at least 4-fold was defined as a recurrent infection...
December 28, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28031361/severe-symptomatic-primary-hcmv-infection-despite-effective-innate-and-adaptive-immune-responses
#14
Raphaëlle Riou, Céline Bressollette-Bodin, David Boutoille, Katia Gagne, Audrey Rodallec, Maeva Lefebvre, François Raffi, David Senitzer, Berthe-Marie Imbert-Marcille, Christelle Retière
: Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. Some rare severe clinical cases have however been reported without investigation of host immune responses or viral virulence. In this present study, we investigate, for the first time, phenotypic and functional features together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty PHIP were enrolled as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28031019/naphthyridines-with-antiviral-activity-a-review
#15
Inder Pal Singh, Sanjay Kumar, Shiv Gupta
BACKGROUND: Naphthyridine scaffold is an important pharmacophore in compounds which have shown various biological activities like antiviral, antimicrobial, anticancer, anti-inflammatory and analgesic etc. This scaffold is also reported to exhibit activity against HIV, HCMV, HSV, HPV and HCV. Antiviral activity displayed by many naphthyridine analogs is in nM range. Only few review articles are available in literature which describe about various biological activities of naphthyridines, but there is no comprehensive compilation particularly for antiviral activities...
December 28, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/28008685/maternal-immune-correlates-of-protection-from-human-cytomegalovirus-transmission-to-the-fetus-after-primary-infection-in-pregnancy
#16
Daniele Lilleri, Giuseppe Gerna
Immune control of primary human cytomegalovirus (HCMV) infection appears to depend on the interaction of humoral and T-cell responses. In this review, we have separately explored the 2 arms of the immune response to primary HCMV infection in HCMV-seronegative pregnant women transmitting (T) or not transmitting (NT) the infection to the fetus, with the objective of correlating the immune risk factors associated with vertical HCMV transmission. As for the humoral response, the following findings were documented: (i) in competitive binding assays, antibody titers to different antigenic sites of the gH pentamer complex were significantly lower in T compared with NT women; (ii) in addition, the number of neutralization sites recognized by T was significantly lower compared with NT women; (iii) the plaque formation inhibition assay showed a faster kinetics and a higher titer in NT women...
December 23, 2016: Reviews in Medical Virology
https://www.readbyqxmd.com/read/28003351/human-microrna-responses-predict-cytomegalovirus-replication-following-solid-organ-transplantation
#17
Sang Hoon Han, D Kumar, V H Ferreira, A Egli, H H Hirsch, M Weisser, C Garzoni, C van Delden, P Y Bochud, O Manuel, P Meylan, K Boggian, S Husain, N J Mueller, A Humar
BACKGROUND: Homo sapiens mature microRNA-200b-3p and -200c-3p are predicted to bind to 3' UTR of mRNA encoding human cytomegalovirus (HCMV) immediate early protein 2 (IE2). We hypothesized that expression of these microRNAs pre-transplant could predict HCMV replication after solid organ transplantation (SOT). METHODS: 272 SOT recipients were HCMV-seropositive pre-transplant and were managed using pre-emptive therapy. Pre-transplant PBMCs were stimulated with HCMV followed by collection of RNA one day post-stimulation...
December 21, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27999668/development-of-a-vivo-rabbit-ligated-intestinal-loop-model-for-hcmv-infection
#18
Jin Tang, Qiaoxing Wu, Xinming Tang, Ruihan Shi, Jingxia Suo, Guangping Huang, Junqing An, Jingyuan Wang, Jinling Yang, Wenzhuo Hao, Ruiping She, Xun Suo
BACKGROUND: Human Cytomegalovirus (HCMV) infections can be found throughout the body, especially in epithelial tissue. Animal model was established by inoculation of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into the ligated sacculus rotundus and vermiform appendix in living rabbits. The specimens were collected from animals sacrificed 1 and a half hours after infection. RESULTS: The virus was found to be capable of reproducing in these specimens through RT-PCR and Western-blot...
2016: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/27990427/positive-expression-of-human-cytomegalovirus-phosphoprotein-65-in-atherosclerosis
#19
Zhe Wang, Jun Cai, Mingming Zhang, Xiaojing Wang, Hongjie Chi, Haijun Feng, Xinchun Yang
Previous studies showed that human cytomegalovirus (HCMV) is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E) and Masson trichrome staining...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27988973/characterizing-human-cytomegalovirus-reinfection-in-congenitally-infected-infants-an-evolutionary-perspective
#20
Cornelia Pokalyuk, Nicholas Renzette, Kristen K Irwin, Susanne P Pfeifer, Laura Gibson, William J Britt, Aparecida Y Yamamoto, Marisa M Mussi-Pinhata, Timothy F Kowalik, Jeffrey D Jensen
Given the strong selective pressures often faced by populations when colonizing a novel habitat, the level of variation present on which selection may act is an important indicator of adaptive potential. While often discussed in an ecological context, this notion is also highly relevant in our clinical understanding of viral infection, in which the novel habitat is a new host. Thus, quantifying the factors determining levels of variation is of considerable importance for the design of improved treatment strategies...
December 18, 2016: Molecular Ecology
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