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https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#1
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#2
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28802146/epigenetic-manipulation-of-host-chromatin-by-kaposi-sarcoma-associated-herpesvirus-a-tumor-promoting-factor
#3
REVIEW
Thomas Günther, Adam Grundhoff
Molecular and epidemiological evidence links Kaposi sarcoma-associated herpesvirus (KSHV) to a number of malignancies of endothelial or B cell origin. As for most virus-associated cancers, however, the tumor initiating and promoting events remain poorly understood. Given the emerging role of epigenetic alterations as drivers of human cancers, an interesting (and as of yet under-explored) hypothesis is that viral manipulation of host cell chromatin may contribute to the pathogenesis of KSHV-associated tumors...
August 9, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28801242/oxidant-species-are-involved-in-t-b-mediated-erk1-2-phosphorylation-that-activates-p53-p21-axis-to-promote-kshv-lytic-cycle-in-pel-cells
#4
Roberta Gonnella, Shivangi Yadav, Maria Saveria Gilardini Montani, Marisa Granato, Roberta Santarelli, Alessia Garufi, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
KSHV is a gammaherpesvirus strongly associated to human cancers such as Primary Effusion Lymphoma (PEL) and Kaposi's Sarcoma. The naturally virus-infected tumor cells usually display latent infection since a minority of cells undergoes spontaneous viral replication. The lytic cycle can be induced in vitro upon appropriate stimuli such as TPA (T), alone or in combination with butyrate (B), (T/B). In previous studies, Protein Kinase C (PKC) δ, Extracellular Signal-regulated Kinase1/2 (ERK1/2) and p53-p21 axis have been separately reported to play a role in KSHV reactivation from latency...
August 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28777778/kshv-and-the-role-of-notch-receptor-dysregulation-in-disease-progression
#5
REVIEW
Jennifer L DeCotiis, David M Lukac
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of two human cancers, Kaposi's Sarcoma (KS) and primary effusion lymphoma (PEL), and a lymphoproliferation, Multicentric Castleman's Disease (MCD). Progression to tumor development in KS is dependent upon the reactivation of the virus from its latent state. We, and others, have shown that the Replication and transcriptional activator (Rta) protein is the only viral gene product that is necessary and sufficient for viral reactivation. To induce the reactivation and transcription of viral genes, Rta forms a complex with the cellular DNA binding component of the canonical Notch signaling pathway, recombination signal binding protein for Jk (RBP-Jk)...
August 4, 2017: Pathogens
https://www.readbyqxmd.com/read/28759216/allosteric-inhibitors-crystallography-and-comparative-analysis-reveal-network-of-coordinated-movement-across-human-herpesvirus-proteases
#6
Timothy M Acker, Jonathan E Gable, Markus-Frederik Bohn, Priyadarshini Jaishankar, Michael C Thompson, James S Fraser, Adam R Renslo, Charles S Craik
Targeting of cryptic binding sites represents an attractive but underexplored approach to modulating protein function with small molecules. Using the dimeric protease (Pr) from Kaposi's sarcoma-associated herpesvirus (KSHV) as a model system, we sought to dissect a putative allosteric network linking a cryptic site at the dimerization interface to enzyme function. Five cryogenic x-ray structures were solved of the monomeric protease with allosteric inhibitors bound to the dimer interface site. Distinct coordinated movements captured by the allosteric inhibitors were also revealed as alternative states in room temperature X-ray data and comparative analyses of other dimeric herpesvirus proteases...
July 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28750175/kaposi-s-sarcoma-associated-herpesvirus-infection-promotes-differentiation-and-polarization-of-monocytes-into-tumor-associated-macrophages
#7
Natarajan Bhaskaran, Santosh K Ghosh, Xiaolan Yu, Sanhai Qin, Aaron Weinberg, Pushpa Pandiyan, Fengchun Ye
Tumor associated macrophages (TAMs) promote angiogenesis, tumor invasion and metastasis, and suppression of anti-tumor immunity. These myeloid cells originate from monocytes, which differentiate into TAMs upon exposure to the local tumor microenvironment. We previously reported that Kaposi's sarcoma-associated herpes virus (KSHV) infection of endothelial cells induces the cytokine angiopoietin-2 (Ang-2) to promote migration of monocytes into tumors. Here we report that KSHV infection of endothelial cells induces additional cytokines including interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) that drive monocytes to differentiate and polarize into TAMs...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28747501/mhv68-expressing-kshv-lana-reveals-both-functional-conservation-and-divergence-in-lana-homologs
#8
Arundhati Gupta, Darby G Oldenburg, Eduardo Salinas, Douglas W White, J Craig Forrest
Latency-associated nuclear antigen (LANA) is a multifunctional protein encoded by members of the Rhadinovirus genus of gammaherpesviruses. Studies using murine gammaherpesvirus 68 (MHV68) demonstrated that LANA is important for acute replication, latency establishment, and reactivation in vivo Despite structural similarities in their DNA-binding domains (DBDs), LANA homologs from Kaposi sarcoma-associated herpesvirus (KSHV) and MHV68 exhibit considerable sequence divergence. We sought to determine if KSHV and MHV68 LANA homologs are functionally interchangeable...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28723706/oral-shedding-of-herpesviruses-in-hiv-patients-with-varying-degrees-of-immune-status
#9
Dirk P Dittmer, Kristen Tamburro, Huichao Chen, Anthony Lee, Marcia K Sanders, Tischan A Wade, Sonia Napravnik, Jennifer Webster-Cyriaque, Mahmoud Ghannoum, Caroline H Shiboski, Judith A Aberg
OBJECTIVE: Herpesvirus shedding in the oral cavity was analyzed to determine if presence in the oral compartment correlates with systemic changes in HIV-associated immune deficiency as measured by CD4+ counts, plasma HIV viral load (VL) and presence of AIDS-defining events. DESIGN: A5254 is a multicenter, cross-sectional, single-visit study to evaluate oral complications of HIV/AIDS and determine the association between clinical appearance, herpesvirus shedding and immune status as ascertained by CD4 count and HIV viral load...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28715488/microrna-dependent-and-independent-deregulation-of-long-non-coding-rnas-by-an-oncogenic-herpesvirus
#10
Sunantha Sethuraman, Lauren Appleby Gay, Vaibhav Jain, Irina Haecker, Rolf Renne
Kaposi's sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28707270/profiling-of-cellular-microrna-responses-during-the-early-stages-of-kshv-infection
#11
Hosni A M Hussein, Shaw M Akula
Kaposi's sarcoma-associated herpesvirus (KSHV) causes a variety of cancers, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Host cellular microRNAs (miRNAs) play important post-transcriptional regulatory roles in gene expression and can greatly influence virus-host cell interactions. This study investigated cellular miRNA expression profiles operating in response to early stages of KSHV infection of human Burkitt lymphoma B cells (BJAB). We employed deep sequencing to analyze miRNA expression in KSHV-infected BJAB cells 15 min post infection (PI) and compared this to uninfected BJAB cells...
July 13, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28704654/persistent-kshv-infection-increases-ebv-associated-tumor-formation-in%C3%A2-vivo-via-enhanced-ebv-lytic-gene-expression
#12
Donal McHugh, Nicole Caduff, Mario Henrique M Barros, Patrick C Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda Capaul, Robert E White, Martin J Allday, Gerald Niedobitek, David J Blackbourn, Adam Grundhoff, Christian Münz
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis...
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28704653/double-the-trouble-when-herpesviruses-join-hands
#13
Un Yung Choi, Angela Park, Jae U Jung
KSHV is the etiologic agent of PEL-an aggressive lymphoma. Interestingly, EBV concurrently exists in nearly 70% of PEL cases. In this issue of Cell Host & Microbe, McHugh et al. (2017) develop humanized mouse models for EBV/KSHV co-infection and identify their complementary effect on in vivo tumor formation.
July 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28701396/effects-of-the-nedd8-activating-enzyme-inhibitor-mln4924-on-lytic-reactivation-of-kaposi-s-sarcoma-associated-herpesvirus
#14
Pey-Jium Chang, Lee-Wen Chen, Li-Yu Chen, Chien-Hui Hung, Ying-Ju Shih, Shie-Shan Wang
The switch of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency to lytic replication is a key event for viral dissemination and pathogenesis. MLN4924, a novel neddylation inhibitor, reportedly causes the onset of KSHV reactivation but impairs later phases of viral lytic program in infected cells. Thus far, the molecular mechanism involved in the modulation of KSHV lytic cycle by MLN4924 is not yet fully understood. Here, we confirmed that treatment of different KSHV-infected primary effusion lymphoma (PEL) cell lines with MLN4924 substantially induces viral lytic protein expression...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28698273/viral-micrornas-repress-the-cholesterol-pathway-and-25-hydroxycholesterol-inhibits-infection
#15
Anna K P Serquiña, Diane M Kambach, Ontara Sarker, Joseph M Ziegelbauer
From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28696226/kaposi-s-sarcoma-associated-herpesvirus-stably-clusters-its-genomes-across-generations-to-maintain-itself-extrachromosomally
#16
Ya-Fang Chiu, Arthur U Sugden, Kathryn Fox, Mitchell Hayes, Bill Sugden
Genetic elements that replicate extrachromosomally are rare in mammals; however, several human tumor viruses, including the papillomaviruses and the gammaherpesviruses, maintain their plasmid genomes by tethering them to cellular chromosomes. We have uncovered an unprecedented mechanism of viral replication: Kaposi's sarcoma-associated herpesvirus (KSHV) stably clusters its genomes across generations to maintain itself extrachromosomally. To identify and characterize this mechanism, we developed two complementary, independent approaches: live-cell imaging and a predictive computational model...
July 10, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28687922/was-kaposi-s-sarcoma-associated-herpesvirus-introduced-into-china-via-the-ancient-silk-road-an-evolutionary-perspective
#17
Zhenqiu Liu, Qiwen Fang, Jialu Zuo, Veenu Minhas, Charles Wood, Na He, Tiejun Zhang
Kaposi's sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road...
July 7, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28687749/inhibition-of-highly-pathogenic-avian-influenza-hpai-virus-by-a-peptide-derived-from-vflip-through-its-direct-destabilization-of-viruses
#18
Ho-Jin Moon, Chamilani Nikapitiya, Hyun-Cheol Lee, Min-Eun Park, Jae-Hoon Kim, Tae-Hwan Kim, Ji-Eun Yoon, Won-Kyung Cho, Jin Yeul Ma, Chul-Joong Kim, Jae U Jung, Jong-Soo Lee
The antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678843/kshv-encoded-orf59-modulates-histone-arginine-methylation-of-the-viral-genome-to-promote-viral-reactivation
#19
Roxanne C Strahan, Maria McDowell-Sargent, Timsy Uppal, Pravinkumar Purushothaman, Subhash C Verma
Kaposi's sarcoma associated herpesvirus (KSHV) persists in a highly-ordered chromatin structure inside latently infected cells with the majority of the viral genome having repressive marks. However, upon reactivation the viral chromatin landscape changes into 'open' chromatin through the involvement of lysine demethylases and methyltransferases. Besides methylation of lysine residues of histone H3, arginine methylation of histone H4 plays an important role in controlling the compactness of the chromatin. Symmetric methylation of histone H4 at arginine 3 (H4R3me2s) negatively affects the methylation of histone H3 at lysine 4 (H3K4me3), an active epigenetic mark deposited on the viral chromatin during reactivation...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28653223/multi-targeted-therapy-of-everolimus-in-kaposi-s-sarcoma-associated-herpes-virus-infected-primary-effusion-lymphoma
#20
Suchitra Mohanty, Amit Kumar, Piyanki Das, Sushil Kumar Sahu, Tathagata Choudhuri
Kaposi's sarcoma associated herpes virus (KSHV) infected primary effusion lymphoma (PEL) is a rare aggressive form of non-Hodgkin's lymphoma of B cells. KSHV latent and lytic antigens modulate several host cellular signalling pathways especially mammalian target of rapamycin (mTOR), STAT-3 and nuclear factor-kappa B (NF-κB) for rapid tumor progression and immune evasion. Current chemotherapeutic strategies are becoming ineffective as they kill only dividing cells and inefficient to target molecular pathways crucial for active virus replication and its survival...
June 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
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