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https://www.readbyqxmd.com/read/29339472/mirna-mediated-targeting-of-human-cytomegalovirus-reveals-biological-host-and-viral-targets-of-ie2
#1
Rasmus Møller, Toni M Schwarz, Vanessa M Noriega, Maryline Panis, David Sachs, Domenico Tortorella, Benjamin R tenOever
Human cytomegalovirus (HCMV) impacts more than one-half of the human population owing to its capacity to manipulate the cell and create latent reservoirs in the host. Despite an extensive understanding of HCMV biology during acute infection in fibroblasts, the molecular basis for latency in myeloid cells remains incomplete. This knowledge gap is due largely to the fact that the existing genetic systems require virus rescue in fibroblasts, precluding the study of genes that are essential during acute infection, yet likely play unique roles in myeloid cells or the establishment of latency...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29330663/human-cytomegalovirus-encoded-mir-ul112-contributes-to-hcmv-mediated-vascular-diseases-by-inducing-vascular-endothelial-cell-dysfunction
#2
Kai Shen, Liyun Xu, Dongdong Chen, Weiguo Tang, Yanyan Huang
Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of vasculopathy by inducing dysfunction of vascular cells such as endothelial cells. Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in the plasma of patients with cardiovascular diseases such as hypertension, while the specific underlying pathophysiological mechanisms are yet to be defined. The current study investigated the effect of hcmv-miR-UL112 on the growth and proliferation of human umbilical vascular endothelial cells (HUVECs); it might also be associated with signaling pathways...
January 12, 2018: Virus Genes
https://www.readbyqxmd.com/read/29328469/human-cytomegalovirus-ul141-protein-interacts-with-celf5-and-affects-viral-dna-replication
#3
Fei Zou, Zhi-Tao Lu, Shuang Wang, Si Wu, Ying-Ying Wu, Zheng-Rong Sun
Human cytomegalovirus (HCMV) infection is the primary viral cause of congenital abnormalities and mental retardation in newborns. The HCMV UL141‑encoded glycoprotein has been previously revealed to inhibit the cell‑surface expression of cluster of differentiation (CD)155, CD122, tumor necrosis factor‑related apoptosis‑inducing ligand death (TRAIL)‑receptor 1 (R1) and TRAIL‑receptor 2 (R2), thus protecting virally‑infected cells by allowing them to escape natural killer cell‑mediated cytotoxicity...
January 10, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321306/digitoxin-suppresses-human-cytomegalovirus-replication-via-na-k-atpase-%C3%AE-1-subunit-dependent-ampk-and-autophagy-activation
#4
Rupkatha Mukhopadhyay, Rajkumar Venkatadri, Jenny Katsnelson, Ravit Arav-Boger
Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report on a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMPK activity and autophagy flux through the Na+, K+/ATPase α1 subunit. Our data illustrate an intricate balance between autophagy regulators AMPK, mTOR and ULK1 during infection and treatment with the cardiac glycoside, digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at unique sites leading to opposing effects on autophagy...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#5
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316040/herpesviruses-viral-loads-and-levels-of-proinflammatory-cytokines-in-apical-periodontitis
#6
Aleksandar Jakovljevic, Aleksandra Knezevic, Nadja Nikolić, Ivan Soldatović, Tanja Jovanovic, Jelena Milasin, Miroslav Andric
OBJECTIVES: This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β, and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines . MATERIALS AND METHODS: 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29301233/analyses-of-tissue-culture-adaptation-of-human-herpesvirus-6a-by-whole-genome-deep-sequencing-redefines-the-reference-sequence-and-identifies-virus-entry-complex-changes
#7
Joshua G Tweedy, Eric Escriva, Maya Topf, Ursula A Gompels
Tissue-culture adaptation of viruses can modulate infection. Laboratory passage and bacterial artificial chromosome (BAC)mid cloning of human cytomegalovirus, HCMV, resulted in genomic deletions and rearrangements altering genes encoding the virus entry complex, which affected cellular tropism, virulence, and vaccine development. Here, we analyse these effects on the reference genome for related betaherpesviruses, Roseolovirus, human herpesvirus 6A (HHV-6A) strain U1102. This virus is also naturally "cloned" by germline subtelomeric chromosomal-integration in approximately 1% of human populations, and accurate references are key to understanding pathological relationships between exogenous and endogenous virus...
December 31, 2017: Viruses
https://www.readbyqxmd.com/read/29298889/a-role-for-myosin-va-in-human-cytomegalovirus-nuclear-egress
#8
Adrian R Wilkie, Mayuri Sharma, Jean M Pesola, Maria Ericsson, Rosio Fernandez, Donald M Coen
Herpesviruses replicate and package their genomes into capsids in replication compartments within the nuclear interior. Capsids then move to the inner nuclear membrane for envelopment and release into the cytoplasm in a process called nuclear egress. We previously found that nuclear F-actin is induced upon infection with the β-herpesvirus, human cytomegalovirus, and is important for nuclear egress and capsid localization away from replication compartment-like inclusions towards the nuclear rim. Despite these and related findings, it has not been shown that any specific motor protein is involved in herpesvirus nuclear egress...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29296946/latent-human-cytomegalovirus-enhances-hiv-1-infection-in-cd34-progenitor-cells
#9
Allen Ka Loon Cheung, Yiru Huang, Hau Yee Kwok, Min Chen, Zhiwei Chen
Individuals who have been preinfected by human cytomegalovirus (HCMV) are more prone to AIDS disease progression after subsequent HIV-1 infection but the underlying mechanism remains elusive. HCMV is a ubiquitous DNA virus that commonly establishes lifelong latent infection in CD34+ progenitor cells, where latency-specific HCMV genes may modulate host restriction to HIV-1 infection. To test this hypothesis, we studied progenitor cells that are known to resist replicative HIV-1 infection because of the intrinsic expression of host restriction factors...
January 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29287989/immune-responses-to-congenital-cytomegalovirus-infection
#10
Ilija Brizić, Lea Hiršl, William J Britt, Astrid Krmpotić, Stipan Jonjić
Human cytomegalovirus (HCMV) is the most common cause of viral infection acquired in utero. Even though the infection has been studied for several decades, immune determinants important for virus control and mechanisms of long-term sequelae caused by infection are still insufficiently characterized. Animal models of congenital HCMV infection provide unique opportunity to study various aspects of human disease. In this review, we summarize current knowledge on the role of immune system in congenital CMV infection, with emphasis on lessons learned from mouse model of congenital CMV infection...
December 26, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29286917/protein-and-dna-evidences-of-hcmv-infection-in-primary-breast-cancer-tissues-and-metastatic-sentinel-lymph-nodes
#11
Jian Cui, Qian Wang, Hai-Bo Wang, Bin Wang, Ling Li
BACKGROUND AND OBJECTIVE: Breast cancer is the leading cause of death in women worldwide. There are evidences that human cytomegalovirus (HCMV) infection is associated with several malignant tumors. This study aims to investigate the infection of human cytomegalovirus (HCMV) in a large sample of breast cancer patients, and conduct a correlation analysis of clinical and pathological factors, to provide evidence for whether HCMV infection is associated with breast cancer development, progression and metastasis...
December 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29286226/almost-complete-lack-of-human-cytomegalovirus-and-human-papillomaviruses-genome-in-benign-and-malignant-breast-lesions-in-shiraz-southwest-of-iran
#12
Sahar Bakhtiyrizadeh, Seyed Younes Hosseini, Ramin Yaghobi, Aliakbar Safaei, Jamal Sarvari
Breast cancer ranks as the most common cancer among women worldwide. There have been controversial reports regarding contributions of human papillomaviruses (HPVs) and human cytomegalovirus (HCMV) to its development. The aim of this study was to determine the frequency of HPV and HCMV positivity in benign and malignant breast tumors. Materials and Methods: Formalin fixed paraffin-embedded tissue specimens of 150 breast cancers (invasive ductal and lobular carcinomas) and 150 non-malignant breast lesions (fibroadenomas, fibrocystic disease and adenosis) were examined...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29276397/is-cytomegalovirus-infection-related-to-inflammatory-bowel-disease-especially-steroid-resistant-inflammatory-bowel-disease-a-meta-analysis
#13
Ya-Li Lv, Fei-Fei Han, Yang-Jie Jia, Zi-Rui Wan, Li-Li Gong, He Liu, Li-Hong Liu
Background: Human cytomegalovirus (HCMV) infection has been associated with inflammatory bowel disease (IBD). Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. Objectives: The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. Study design: We identified relevant studies through a search of PubMed and Embase...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29274844/repurposing-the-clinically-approved-calcium-antagonist-manidipine-dihydrochloride-as-a-new-early-inhibitor-of-human-cytomegalovirus-targeting-the-immediate-early-2-ie2-protein
#14
Beatrice Mercorelli, Anna Luganini, Marta Celegato, Giorgio Palù, Giorgio Gribaudo, Arianna Loregian
Currently, there are no therapeutic alternatives to DNA polymerase inhibitors to treat human cytomegalovirus (HCMV) infections, a major threat for immunocompromised patients and pregnant women. Here, we explored the potential to repurpose manidipine dihydrochloride (MND), a calcium antagonist clinically approved to treat hypertension, as a new anti-HCMV agent. MND emerged in a previous drug repurposing screen to find early inhibitors of HCMV replication, and now we confirm that it inhibits in the low micromolar range the replication of different HCMV strains, including clinical isolates and viruses resistant to approved DNA polymerase inhibitors...
December 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29237845/human-cytomegalovirus-replication-is-inhibited-by-the-autophagy-inducing-compounds-trehalose-and-smer28-through-distinctively-different-mechanisms
#15
Alex E Clark, Maite Sabalza, Philip L S M Gordts, Deborah H Spector
Human Cytomegalovirus (HCMV) is the top viral cause of birth defects worldwide, and current therapies have high toxicity. We previously published that the mTOR-independent autophagy-inducing disaccharide trehalose inhibits HCMV replication in multiple cell types. Here, we examine the mechanism of inhibition and introduce the autophagy inducer SMER28 as an additional inhibitor of HCMV acting through a different mechanism. We find that trehalose induces vacuolation and acidification of vacuoles, and that debris, including debris consistent in appearance with abnormal virions, is present in multivesicular bodies...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237840/human-cytomegalovirus-ul111a-and-us27-gene-products-enhance-the-cxcl12-cxcr4-signaling-axis-via-distinct-mechanisms
#16
Carolyn C Tu, Kathleen L Arnolds, Christine M O'Connor, Juliet V Spencer
Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29228551/human-cytomegalovirus-and-herpes-simplex-type-i-virus-can-engage-rna-polymerase-i-for-transcription-of-immediate-early-genes
#17
Ourania N Kostopoulou, Vanessa Wilhelmi, Sina Raiss, Sharan Ananthaseshan, Mikael S Lindström, Jiri Bartek, Cecilia Söderberg-Naucler
Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226181/a-bioreactor-method-to-generate-high-titer-genetically-stable-clinical-isolate-human-cytomegalovirus
#18
Victoria R Saykally, Luke I Rast, Jeff Sasaki, Seung-Yong Jung, Cynthia Bolovan-Fritts, Leor S Weinberger
Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in transplant patients and a leading cause of congenital birth defects (Saint Louis, 2016). Vaccination and therapeutic studies often require scalable cell culture production of wild type virus, represented by clinical isolates. Obtaining sufficient stocks of wild-type clinical HCMV is often labor intensive and inefficient due to low yield and genetic loss, presenting a barrier to studies of clinical isolates. Here we report a bioreactor method based on continuous infection, where retinal pigment epithelial (ARPE-19) cells adhered to microcarrier beads are infected in a bioreactor and used to produce high-titers of clinical isolate HCMV that maintain genetic integrity of key viral tropism factors and the viral genome...
November 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29220498/nkg2c-deletion-is-a-risk-factor-for-human-cytomegalovirus-viremia-and-disease-after-lung-transplantation
#19
Hannes Vietzen, Karin Pollak, Claudia Honsig, Peter Jaksch, Elisabeth Puchhammer-Stöckl
Human cytomegalovirus (HCMV) replication is limited by HCMV-specific natural-killer (NK) cell response. Distinct genetic polymorphisms, which are potentially involved in antiviral NK-cell response, have been described. Here, the association between polymorphisms at IgG1 GM3/17, FcγRIIIα/CD16a-158V/F, NKG2Cwt/del, CD226/rs727088 and rs763361, respectively, and HCMV-viremia and disease was investigated in 98 lung transplant recipients (LTRs), within 9 months after stop of post-transplant HCMV-prophylaxis. From all variants, only the NKG2Cwt/wt genotype was significantly associated with freedom from HCMV-viremia (P= 0...
December 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#20
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
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