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https://www.readbyqxmd.com/read/28446671/kaposi-s-sarcoma-herpesvirus-latency-associated-nuclear-antigen-lana-replicating-and-shielding-viral-dna-during-viral-persistence
#1
Magdalena Weidner-Glunde, Giuseppe Mariggiò, Thomas F Schulz
Kaposi's sarcoma herpesvirus (KSHV) establishes life-long latency. The viral latency-associated nuclear antigen (LANA) promotes viral persistence by tethering the viral genome to cellular chromosomes and by participating in latent DNA replication. Recently, the structure of the LANA C-terminal DNA binding domain was solved and new cytoplasmic variants of LANA were discovered. We discuss how these findings contribute to our current view of LANA structure, assembly and its role during viral persistence.
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28443092/disarming-cellular-alarm-systems-manipulation-of-stress-induced-nkg2d-ligands-by-human-herpesviruses
#2
REVIEW
Dominik Schmiedel, Ofer Mandelboim
The coevolution of viruses and their hosts led to the repeated emergence of cellular alert signals and viral strategies to counteract them. The herpesvirus family of viruses displays the most sophisticated repertoire of immune escape mechanisms enabling infected cells to evade immune recognition and thereby maintain infection. The herpesvirus family consists of nine viruses that are capable of infecting humans: herpes simplex virus 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), roseoloviruses (HHV-6A, HHV-6B, and HHV-7), and Kaposi's-sarcoma-associated herpesvirus (KSHV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28430817/kaposi-sarcoma-herpesvirus-kshv-latency-associated-nuclear-antigen-lana-recruits-components-of-the-mrn-mre11-rad50-nbs1-repair-complex-to-modulate-an-innate-immune-signaling-pathway-and-viral-latency
#3
Giuseppe Mariggiò, Sandra Koch, Guigen Zhang, Magdalena Weidner-Glunde, Jessica Rückert, Semra Kati, Susann Santag, Thomas F Schulz
Kaposi Sarcoma Herpesvirus (KSHV), a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS), Primary Effusion Lymphoma (PEL) and Multicentric Castleman's Disease (MCD). Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway...
April 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28421060/the-heme-metabolite-carbon-monoxide-facilitates-kshv-infection-by-inhibiting-tlr4-signaling-in-endothelial-cells
#4
Sara Botto, Jean K Gustin, Ashlee V Moses
Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS) and certain rare B cell lymphoproliferative disorders. KSHV infection of endothelial cells (EC) in vitro increases expression of the inducible host-encoded enzyme heme oxygenase-1 (HO-1), which is also strongly expressed in KS tumors. HO-1 catalyzes the rate-limiting step in the conversion of heme into iron, biliverdin and the gasotransmitter carbon monoxide (CO), all of which share anti-apoptotic, anti-inflammatory, pro-survival, and tumorigenic activities...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28415759/kshv-co-infection-down-regulates-hpv16-e6-and-e7-from-cervical-cancer-cells
#5
Lu Dai, Yueyu Cao, Wei Jiang, Jovanny Zabaleta, Zhongmin Liu, Jing Qiao, Zhiqiang Qin
High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oral and oropharyngeal cancers. Kaposi sarcoma-associated herpesvirus (KSHV) represents a principal causative agent of several human cancers arising in those immunocompromised patients. Interestingly, KSHV DNA has been detected in the oral cavity and the female genital tract, although its detection rate in cervical samples is very low and few reports are about KSHV/HPV co-infection. Therefore, it remains unclear about the role of KSHV co-infection in the development of HPV-related neoplasias...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407694/molecular-mechanisms-of-activating-c-met-in-kshv-primary-effusion-lymphoma
#6
Bao Quoc Lam, Lu Dai, Li Li, Jing Qiao, Zhen Lin, Zhiqiang Qin
The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404899/balb-c-mice-immunized-with-a-combination-of-virus-like-particles-incorporating-kaposi-sarcoma-associated-herpesvirus-kshv-envelope-glycoproteins-gpk8-1-gb-and-gh-gl-induced-comparable-serum-neutralizing-antibody-activity-to-uv-inactivated-kshv
#7
Anne K Barasa, Peng Ye, Meredith Phelps, Ganapathiram T Arivudainambi, Timelia Tison, Javier Gordon Ogembo
Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring in Africa, where the virus is endemic. To date, there is no prophylactic vaccine against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus entry into host cells, are attractive vaccine targets for eliciting potent neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1, gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized these VLPs for their composition, size, and functionality...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395104/hhv8-kshv-positive-lymphoproliferative-disorders-and-the-spectrum-of-plasmablastic-and-plasma-cell-neoplasms-2015-sh-eahp-workshop-report-part-3
#8
Amy Chadburn, Jonathan Said, Dita Gratzinger, John K C Chan, Daphne de Jong, Elaine S Jaffe, Yasodha Natkunam, John R Goodlad
Objectives: The 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review immunodeficiency-related lymphoproliferative disorders with plasmablastic and plasma cell differentiation. Methods: The workshop panel reviewed human herpes virus 8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV)-associated lesions and other lesions exhibiting plasma cell differentiation, including plasmablastic proliferations with features of myeloma/plasmacytoma, plasmablastic neoplasms presenting in extranodal sites and effusion-based lymphomas, and rendered a consensus diagnosis...
February 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28383682/kaposi-s-sarcoma-associated-herpesvirus-polyadenylated-nuclear-rna-a-structural-scaffold-for-nuclear-cytoplasmic-and-viral-proteins
#9
Joanna Sztuba-Solinska, Jason W Rausch, Rodman Smith, Jennifer T Miller, Denise Whitby, Stuart F J Le Grice
Kaposi's sarcoma-associated herpes virus (KSHV) polyadenylated nuclear (PAN) RNA facilitates lytic infection, modulating the cellular immune response by interacting with viral and cellular proteins and DNA. Although a number nucleoprotein interactions involving PAN have been implicated, our understanding of binding partners and PAN RNA binding motifs remains incomplete. Herein, we used SHAPE-mutational profiling (SHAPE-MaP) to probe PAN in its nuclear, cytoplasmic or viral environments or following cell/virion lysis and removal of proteins...
April 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28380040/an-ape1-inhibitor-reveals-critical-roles-of-the-redox-function-of-ape1-in-kshv-replication-and-pathogenic-phenotypes
#10
Canrong Zhong, Mengyang Xu, Yan Wang, Jun Xu, Yan Yuan
APE1 is a multifunctional protein with a DNA base excision repair function in its C-terminal domain and a redox activity in its N-terminal domain. The redox function of APE1 converts certain transcription factors from inactive oxidized to active reduced forms. Given that among the APE1-regulated transcription factors many are critical for KSHV replication and pathogenesis, we investigated whether inhibition of APE1 redox function blocks KSHV replication and Kaposi's sarcoma (KS) phenotypes. With an shRNA-mediated silencing approach and a known APE-1 redox inhibitor, we demonstrated that APE1 redox function is indeed required for KSHV replication as well as KSHV-induced angiogenesis, validating APE1 as a therapeutic target for KSHV-associated diseases...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28376153/evidence-for-a-mesothelial-origin-of-body-cavity-effusion-lymphomas
#11
David Sanchez-Martin, Thomas S Uldrick, Hyeongil Kwak, Hidetaka Ohnuki, Mark N Polizzotto, Christina M Annunziata, Mark Raffeld, Kathleen M Wyvill, Karen Aleman, Victoria Wang, Vickie A Marshall, Denise Whitby, Robert Yarchoan, Giovanna Tosato
Background: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma herpes virus (KSHV)-induced lymphoma that typically arises in body cavities of HIV-infected patients. PEL cells are often co-infected with Epstein-Barr virus (EBV). "PEL-like" lymphoma is a KSHV-unrelated lymphoma that arises in body cavities of HIV-negative patients. "PEL-like" lymphoma is sometimes EBV positive. The derivation of PEL/"PEL-like" cells is unclear. Methods: Mesothelial cells were cultured from body cavity effusions of 23 patients...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28342865/kshv-encoded-viral-interferon-regulatory-factor-4-virf4-interacts-with-irf7-and-inhibits-interferon-alpha-production
#12
Sung-Woo Hwang, DongIk Kim, Jae U Jung, Hye-Ra Lee
Before an infection can be completely established, the host immediately turns on the innate immune system through activating the interferon (IFN)-mediated antiviral pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) utilizes a unique antagonistic mechanism of type I IFN-mediated host antiviral immunity by incorporating four viral interferon regulatory factors (vIRF1-4). Herein, we characterized novel immune evasion strategies of vIRF4 to inhibit the IRF7-mediated IFN-α production. KSHV vIRF4 specifically interacts with IRF7, resulting in inhibition of IRF7 dimerization and ultimately suppresses IRF7-mediated activation of type I IFN...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28336944/kaposi-s-sarcoma-associated-herpesvirus-orf34-is-essential-for-late-gene-expression-and-virus-production
#13
Mayu Nishimura, Tadashi Watanabe, Syota Yagi, Takahiro Yamanaka, Masahiro Fujimuro
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV establishes a life-long infection in its host and alternates between a latent and lytic infection state. During lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. ORF34 is an early-late gene that interacts with several viral transcription-associated factors, however its physiological importance remains poorly understood...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335496/quantitative-analysis-of-the-kshv-transcriptome-following-primary-infection-of-blood-and-lymphatic-endothelial-cells
#14
A Gregory Bruce, Serge Barcy, Terri DiMaio, Emilia Gan, H Jacques Garrigues, Michael Lagunoff, Timothy M Rose
The transcriptome of the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) after primary latent infection of human blood (BEC), lymphatic (LEC) and immortalized (TIME) endothelial cells was analyzed using RNAseq, and compared to long-term latency in BCBL-1 lymphoma cells. Naturally expressed transcripts were obtained without artificial induction, and a comprehensive annotation of the KSHV genome was determined. A set of unique coding sequence (UCDS) features and a process to resolve overlapping transcripts were developed to accurately quantitate transcript levels from specific promoters...
March 19, 2017: Pathogens
https://www.readbyqxmd.com/read/28333859/multicenter-prospective-study-for-laboratory-diagnosis-of-hhv8-infection-in-solid-organ-donors-and-transplant-recipients-and-evaluation-of-the-clinical-impact-after-transplantation
#15
Angela Chiereghin, Patrizia Barozzi, Evangelia Petrisli, Giulia Piccirilli, Liliana Gabrielli, Giovanni Riva, Leonardo Potenza, Gianni Cappelli, Nicola De Ruvo, Irene Libri, Umberto Maggiore, Maria Cristina Morelli, Luciano Potena, Paola Todeschini, Dino Gibertoni, Manuel Labanti, Gabriela Sangiorgi, Gaetano La Manna, Antonio Daniele Pinna, Mario Luppi, Tiziana Lazzarotto
BACKGROUND: We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north-central Italy and a surveillance program for human herpes virus 8 (HHV8) infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients. METHODS: For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays (IFA) and 2 enzyme-linked immunosorbent assays (ELISA) - both HHV8 lytic and latent antigen-based) and 2 molecular assays were used...
March 22, 2017: Transplantation
https://www.readbyqxmd.com/read/28331082/kaposi-s-sarcoma-associated-herpesvirus-hijacks-rna-polymerase-ii-to-create-a-viral-transcriptional-factory
#16
Christopher Phillip Chen, Yuanzhi Lyu, Frank Chuang, Kazushi Nakano, Chie Izumiya, Di Jin, Mel Campbell, Yoshihiro Izumiya
Locally concentrated nuclear factors ensure efficient binding to the DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable pre-initiation complexes. Here we have uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around KSHV genomes in the host cell nucleus. Using immunofluorescent labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hybridization (RNA-FISH) of the intron region of immediate-early transcripts, we visualized active transcription of viral genomes in naturally infected cells...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28324233/diagnosis-and-treatment-of-kaposi-sarcoma
#17
REVIEW
Johann W Schneider, Dirk P Dittmer
Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy...
March 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28323040/-machine-learning-based-identification-of-endogenous-cellular-microrna-sponges-against-viral-micrornas
#18
Soowon Kang, Seunghyun Park, Sungroh Yoon, Hyeyoung Min
A "miRNA sponge" is an artificial oligonucleotide-based miRNA inhibitor containing multiple binding sites for a specific miRNA. Each miRNA sponge can bind and sequester several miRNA copies, thereby decreasing the cellular levels of the target miRNA. In addition to developing artificial miRNA sponges, scientists have sought endogenous RNA transcripts and found that long non-coding RNAs, competing endogenous RNAs, pseudogenes, circular RNAs, and coding RNAs could act as miRNA sponges under precise conditions...
March 17, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28288847/increased-frequency-and-vasculogenic-potential-of-endothelial-colony-forming-cells-in-patients-with-kaposi-s-sarcoma
#19
Francesca Calcaterra, Lucia Brambilla, Elena Colombo, Athanasia Tourlaki, Stefano Veraldi, Claudia Carenza, Domenico Mavilio, Silvia Della Bella
Kaposi's sarcoma (KS) is characterized by hyperproliferation of spindle cells that have an endothelial origin and assume their characteristic features upon infection with human herpesvirus-8 (HHV8), the causative agent for KS. The multifocal nature of KS suggests that spindle cells derive from circulating HHV8-infected precursors that yet lack identification. We investigated whether ECFCs obtained from KS patients may be putative precursors of spindle cells, by assessing whether their in vitro behavior may evoke the in vivo behavior of KS spindle cells...
March 10, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28284028/modulation-of-oncogenic-signaling-networks-by-kaposi-s-sarcoma-associated-herpesvirus
#20
REVIEW
Jason P Wong, Blossom Damania
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. To persist and replicate within host cells, KSHV encodes proteins that modulate different signaling pathways. Manipulation of cell survival and proliferative networks by KSHV can promote the development of KSHV-associated malignancies. In this review, we discuss recent updates on KSHV pathogenesis and the viral life cycle. We focus on proteins encoded by KSHV that modulate the phosphatidylinositol-4,5-bisphosphate 3 kinase and extracellular signal-regulated kinases 1/2 pathways to create an environment favorable for viral replication and the development of KSHV malignancies...
April 21, 2017: Biological Chemistry
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