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https://www.readbyqxmd.com/read/28533400/the-pentameric-complex-drives-immunologically-covert-cell-cell-transmission-of-wild-type-human-cytomegalovirus
#1
Isa Murrell, Carmen Bedford, Kristin Ladell, Kelly L Miners, David A Price, Peter Tomasec, Gavin W G Wilkinson, Richard J Stanton
Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation with a virus that retained a clinically relevant phenotype, we reconstructed a wild-type (WT) HCMV genome using bacterial artificial chromosome technology. Like clinical virus, this genome proved to be unstable in cell culture; however, propagation of intact virus was achieved by placing the RL13 and UL128 genes under conditional expression...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28523518/decreased-human-leukocyte-antigen-a-02-01-frequency-is-associated-with-risk-of-glioma-and-existence-of-human-cytomegalovirus-a-case-control-study-in-northern-china
#2
Sheng Han, Jian Deng, Zixun Wang, Huan Liu, Wen Cheng, Anhua Wu
BACKGROUND: Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. METHODS: The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender...
May 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28513970/cytomegalovirus-infection-and-atherosclerosis-risk-a-meta-analysis
#3
Yang-Jie Jia, Jun Liu, Fei-Fei Han, Zi-Rui Wan, Li-Li Gong, He Liu, Wen Zhang, Thomas Wardell, Ya-Li Lv, Li-Hong Liu
BACKGROUND: Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. METHODS: Relative literature was searched through the electronic databases PubMed, Embase, and CNKI...
May 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28501424/ro0504985-is-an-inhibitor-of-cmgc-kinase-proteins-and-has-anti-human-cytomegalovirus-activity
#4
Blair L Strang
Public-private partnerships allow many previously unavailable compounds to be screened for antiviral activity. Here a screening method was used to identify an oxindole compound, RO0504985, from a Roche kinase inhibitor library that inhibited human cytomegalovirus (HCMV) protein production. RO0504985 was previously described as an inhibitor of cyclin-dependent kinase 2 (CDK2). However, using kinase selectivity assays it was found that RO0504985 was an inhibitor of several CMGC group kinase proteins, including CDK2...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28494195/functionally-inactivated-dominant-viral-antigens-of-human-cytomegalovirus-delivered-in-replication-incompetent-adenovirus-type-6-vectors-as-vaccine-candidates
#5
Aimin Tang, Daniel C Freed, Fengsheng Li, Steve Meschino, Michael Prokop, Andrew Bett, Danilo Casimiro, Dai Wang, Tong-Ming Fu
T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection in transplant recipients, and T cells targeting viral immediate early proteins such as IE1, IE2 and pp65 have been speculated to be more effective against reactivation. Here we report efforts to construct replication incompetent adenovirus 6 vectors expressing these viral antigens as vaccine candidates. To reduce the potential liabilities of these viral proteins as vaccine antigens, we introduced mutations to inactivate their reported functions including their nuclear localization signals...
May 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28494016/the-host-ubiquitin-dependent-segregase-vcp-p97-is-required-for-the-onset-of-human-cytomegalovirus-replication
#6
Yao-Tang Lin, James Prendergast, Finn Grey
The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28491945/reference-values-for-t-b-and-nk-human-lymphocyte-subpopulations-in-adults
#7
P A Apoil, B Puissant-Lubrano, N Congy-Jolivet, M Peres, J Tkaczuk, F Roubinet, A Blancher
The data presented in this paper are reference ranges for frequencies of thirty-eight subpopulations of T, B and NK lymphocytes, established from a cohort of 253 healthy blood donors aged from 19 to 67. When relevant, the influence of age or sex was taken into account to calculate these reference values. This article is related to the research article entitled "Influence of age, sex and HCMV-serostatus on blood lymphocyte subpopulations in healthy adults" (Apoil et al., 2017) [1]. Immunophenotyping data obtained from each individual is made publicly available for extended analyses...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28491825/hcmv-activation-of-erk-mapk-drives-a-multi-factorial-response-promoting-the-survival-of-infected-myeloid-progenitors
#8
Verity Kew, Mark Wills, Matthew Reeves
Viral binding and entry provides the first trigger of a cell death response and thus how human cytomegalovirus (HCMV) evades this - particularly during latent infection where a very limited pattern of gene expression is observed - is less well understood. It has been demonstrated that the activation of cellular signalling pathways upon virus binding promotes the survival of latently infected cells by the activation of cell encoded anti-apoptotic responses. In CD34+ cells, a major site of HCMV latency, ERK signalling is important for survival and we now show that the activation of this pathway impacts on multiple aspects of cell death pathways...
2017: Journal of Molecular Biochemistry
https://www.readbyqxmd.com/read/28490582/congenital-hcmv-infection-and-the-enigma-of-maternal-immunity
#9
William J Britt
Human cytomegalovirus (HCMV) is the most common viral infection acquired by the developing human fetus and can result in damage to the developing CNS. Although vaccine development to modify this congenital infection is ongoing, the unique epidemiology of maternal HCMV infections appears discordant with strategies for vaccine development. Several characteristics of congenital HCMV infections suggest that the efficacy of vaccines designed to induce responses similar to those that follow natural infection will be limited...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28484459/human-cytomegalovirus-induced-degradation-of-cytip-modulates-dendritic-cell-adhesion-and-migration
#10
Linda Grosche, Christina Draßner, Petra Mühl-Zürbes, Lisa Kamm, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Alexander Steinkasserer, Christiane S Heilingloh
As potent antigen-presenting cells, dendritic cells (DCs) are essential for the initiation of effective antiviral immune responses. Viruses and especially herpesviruses, which are able to establish lifelong persistence, exploit several immune evasion mechanisms targeting DC biology. Our group has previously shown that the α-herpesvirus herpes simplex virus type 1 inhibits mature DC (mDC) migration by inducing adhesion via degrading the cellular protein CYTIP (cytohesin-1 interacting protein), an important negative regulator of β2-integrin activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484438/the-role-of-hcmv-and-hiv-1-micrornas-processing-and-mechanisms-of-action-during-viral-infection
#11
REVIEW
Doriana Fruci, Rossella Rota, Angela Gallo
Viruses infect host cells releasing their genome (DNA or RNA) containing all information needed to replicate themselves. The viral genome takes control of the cells and helps the virus to evade the host immune system. Some viruses alter the functions of infected cells without killing them. In some cases infected cells lose control over normal cell proliferation and becomes cancerous. Viruses, such as HCMV and HIV-1, may leave their viral genome in the host cells for a certain period (latency) and begin to replicate when the cells are stressed causing diseases...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28480966/human-cytomegalovirus-triggers-the-assembly-of-aim2-inflammasome-in-thp-1-derived-macrophages
#12
Yuan Huang, Lingling Liu, Di Ma, Yi Liao, Yuanyuan Lu, Heyu Huang, Wenqing Qin, Xinglou Liu, Feng Fang
Absent in melanoma 2 (AIM2) inflammasome is a multiprotein complex which plays a pivotal role in the host immune response to multiple pathogens. The role of AIM2 in human cytomegalovirus (HCMV) infection is poorly studied. Thus, using a small inference RNA (siRNA) approach and THP-1 derived macrophage cells infected with HCMV AD169 strain, we investigated the impact of HCMV infection on AIM2-mediated molecular events. Compared to wild-type cells, AIM2-defiecient macrophages showed a limited ability to activate caspase-1, process IL-1β, and induce cell death...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28475279/nk-cells-generate-memory-type-responses-to-human-cytomegalovirus-infected-fibroblasts
#13
Nicholas Newhook, Neva Fudge, Michael Grant
Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C(+) CD57(+) NK cells in vivo and NKG2C(+) NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon-γ (IFN-γ) production of NK cells from HCMV-seropositive and HCMV-seronegative individuals co-cultured with HCMV-infected or uninfected MRC-5 cells...
May 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28473657/human-cytomegalovirus-immediate-early-protein-promotes-survival-of-glioma-cells-through-interacting-and-acetylating-atf5
#14
Ming Hu, Bin Wang, Dongmeng Qian, Mengyuan Wang, Rui Huang, Li Wei, Ling Li, Li Zhang, David X Liu
Human cytomegalovirus (HCMV), a widespread beta-herpes virus, infects a high percentage of gliomas. HCMV is specifically detected in human gliomas at a low level of expression raises the possibility that it may regulate the malignant phenotype in a chronic manner. Although HCMV is not recognized as an oncogenic virus, it might dysregulate signaling pathways involved in initiation and promotion of malignancy.Here, our immunohistochemical staining reveals that nucleus staining of the HCMV 86-kDa immediate-early protein (IE86) is markedly increased in GBM (58...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28467444/human-cytomegalovirus-glycoprotein-polymorphisms-and-increasing-viral-load-in-aids-patients
#15
Xiao-Jing Jiang, Jun Zhang, Yong Xiong, Gerhard Jahn, Hai-Rong Xiong, Zhan-Qiu Yang, Yuan-Yuan Liu
BACKGROUND: Multiple strains infection of human cytomegalovirus (HCMV) was found to be correlated with increased viral load in immunodeficient patients. However, the pathogenic mechanism underlying this correlation remains unclear. To evaluate genetic polymorphisms of HCMV glycoprotein and their potential role in its viral load, HCMV glycoprotein B, N, and O (gB, gN and gO) genotypes was studied in the population of HCMV infected acquired immune deficiency syndrome (AIDS) patients. The association between glycoprotein polymorphisms and HCMV viral load was analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28462939/facile-access-to-potent-antiviral-quinazoline-heterocycles-with-fluorescence-properties-via-merging-metal-free-domino-reactions
#16
Felix E Held, Anton A Guryev, Tony Fröhlich, Frank Hampel, Axel Kahnt, Corina Hutterer, Mirjam Steingruber, Hanife Bahsi, Clemens von Bojničić-Kninski, Daniela S Mattes, Tobias C Foertsch, Alexander Nesterov-Mueller, Manfred Marschall, Svetlana B Tsogoeva
Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties (EC50 down to 0...
May 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28456432/maternal-immune-correlates-of-protection-against-placental-transmission-of-cytomegalovirus
#17
Hannah L Itell, Cody S Nelson, David R Martinez, Sallie R Permar
Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. In a subset of infected infants, congenital HCMV causes severe, long-lasting sequelae, including deafness, microcephaly, neurodevelopmental delay, and even death. Accordingly, a maternal vaccine to prevent congenital HCMV infection continues to be a top public health priority. Nevertheless, all vaccines tested to date have failed to meet clinical trial endpoints. Maternal immunity provides partial protection against congenital HCMV transmission, as vertical transmission from seropositive mothers is relatively rare...
April 20, 2017: Placenta
https://www.readbyqxmd.com/read/28454912/phosphonoamidate-prodrugs-of-c5-substituted-pyrimidine-acyclic-nucleosides-for-antiviral-therapy
#18
Fabrizio Pertusati, Sara Serafini, Najmiyah Albadry, Robert Snoeck, Graciela Andrei
Acyclic nucleoside phosphonates (ANPs) are nowadays one of the key drugs in the treatment of DNA virus and retrovirus infections. In this work, we report the synthesis and antiviral evaluation of phosphonoamidate and diamidates prodrugs of C5-pyrimidine acyclic nucleosides derivatives functionalized with but-2-enyl- chain. In the phosphonoamidate series, the most active compound 15, showed sub-micromolar activity against varicella zoster virus (VZV) (EC50 = 0.09-0.5 μM) and μM activity against human cytomegalovirus (HCMV) and herpes simplex virus (HSV)...
April 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28453840/modulation-of-the-host-environment-by-human-cytomegalovirus-with-viral-interleukin-10-in-peripheral-blood
#19
Vivian P Young, Margarette C Mariano, Carolyn C Tu, Kathryn M Allaire, Selmir Avdic, Barry Slobedman, Juliet V Spencer
Background.: Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and latent life cycles. Human cytomegalovirus encodes 2 viral cytokines that are orthologs of human cellular interleukin 10 (cIL-10). Both cytomegalovirus interleukin 10 (cmvIL-10) and Latency-associated cytomegalovirus interleukin 10 (LAcmvIL-10) (collectively vIL-10) are expressed during lytic infection and cause immunosuppressive effects that impede virus clearance. LAcmvIL-10 is also expressed during latent infection of myeloid progenitor cells and monocytes and facilitates persistence...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28451898/human-cytomegalovirus-infection-dysregulates-neural-progenitor-cell-fate-by-disrupting-hes1-rhythm-and-down-regulating-its-expression
#20
Xi-Juan Liu, Xuan Jiang, Sheng-Nan Huang, Jin-Yan Sun, Fei Zhao, Wen-Bo Zeng, Min-Hua Luo
Human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor /stem cells (NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately 1.5 hour periodicity and a Hes1 protein half-life of about 17 (17...
April 24, 2017: Virologica Sinica
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