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https://www.readbyqxmd.com/read/29342139/structure-and-mutagenesis-reveal-essential-capsid-protein-interactions-for-kshv-replication
#1
Xinghong Dai, Danyang Gong, Hanyoung Lim, Jonathan Jih, Ting-Ting Wu, Ren Sun, Z Hong Zhou
Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 Å in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29339432/deregulation-of-hdac5-by-viral-interferon-regulatory-factor-3-plays-an-essential-role-in-kaposi-s-sarcoma-associated-herpesvirus-induced-lymphangiogenesis
#2
Hye-Ra Lee, Fan Li, Un Yung Choi, Hye Ryun Yu, Grace M Aldrovandi, Pinghui Feng, Shou-Jiang Gao, Young-Kwon Hong, Jae U Jung
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29321307/kaposi-s-sarcoma-associated-herpesvirus-k8-is-an-rna-binding-protein-that-regulates-viral-dna-replication-in-coordination-with-a-noncoding-rna
#3
Dongcheng Liu, Yan Wang, Yan Yuan
KSHV lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. Virus-encoded b-Zip family protein K8 plays an important role in viral DNA replication in both viral reactivation and de novo infection. The mechanism underlying the functional role of K8 in the viral life cycle is elusive. Here we report that K8 is a RNA binding protein, which also associates with many proteins including other RNA binding proteins. Many K8-involved protein-protein interactions are mediated by RNA...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29312617/t-cell-responses-to-kshv-infection-a-systematic-approach
#4
Romin Roshan, Nazzarena Labo, Matthew Trivett, Wendell Miley, Vickie Marshall, Lori Coren, Elena M Cornejo Castro, Hannah Perez, Benjamin Holdridge, Eliza Davis, Rodrigo Matus-Nicodemos, Victor I Ayala, Raymond Sowder, Kathleen M Wyvill, Karen Aleman, Christine Fennessey, Jeffrey Lifson, Mark N Polizzotto, Daniel Douek, Brandon Keele, Thomas S Uldrick, Robert Yarchoan, Claes Ohlen, David Ott, Denise Whitby
Prior studies of T-cell responses to KSHV have included relatively few participants and focused on relatively few KSHV antigens. To provide a more comprehensive analysis, we investigated T-cell responses to the whole KSHV proteome using IFN-γ ELISpot. Using ∼7,500 overlapping 15mer peptides we generated one to three peptide pools for each of the 82 KSHV ORFs. IFN-γ ELISpot analysis of PBMCs from 19 patients with a history of KSHV-associated disease and 24 healthy donors (11 KSHV seropositive) detected widely varied responses...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29302027/kshv-episomes-reveal-dynamic-chromatin-loop-formation-with-domain-specific-gene-regulation
#5
Mel Campbell, Tadashi Watanabe, Kazushi Nakano, Ryan R Davis, Yuanzhi Lyu, Clifford G Tepper, Blythe Durbin-Johnson, Masahiro Fujimuro, Yoshihiro Izumiya
The three-dimensional structure of chromatin organized by genomic loops facilitates RNA polymerase II access to distal promoters. The Kaposi's sarcoma-associated herpesvirus (KSHV) lytic transcriptional program is initiated by a single viral transactivator, K-Rta. Here we report the KSHV genomic structure and its relationship with K-Rta recruitment sites using Capture Hi-C analyses. High-resolution 3D viral genomic maps identify a number of direct physical, long-range, and dynamic genomic interactions. Mutant KSHV chromosomes harboring point mutations in the K-Rta responsive elements (RE) significantly attenuate not only the directly proximate downstream gene, but also distal gene expression in a domain-specific manner...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29245944/extracellular-vesicles-from-kshv-infected-endothelial-cells-activate-the-complement-system
#6
Hyungtaek Jeon, Seung-Min Yoo, Hyo Sun Choi, Ji Young Mun, Hee-Gyoo Kang, Jiyeong Lee, Jinsung Park, Shou-Jiang Gao, Myung-Shin Lee
Extracellular vesicles (EVs), released by cells, are associated with cell-to-cell communication and regulate various cellular processes. EVs draw parallels with viruses for their similar structures and functions. Increasing evidences from recent studies indicate that cells infected with viruses release a variety of EVs. Delineating the functions and mechanisms of EVs released during virus infection is essential for understanding the molecular basis of viral infection and replication as well as associated pathogenesis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29244209/generation-of-a-kshv-k13-deletion-mutant-for-vflip-function-study
#7
Fei Wang, Yuanyuan Guo, Wan Li, Chun Lu, Qin Yan
Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral Fas-associated death domain-like IL-1-converting enzyme inhibitory protein (vFLIP) is one of the latently expressed genes and plays a key role in cell survival and maintenance of latent infection by activating the NF-κB pathway. To obtain a genetic system for studying KSHV vFLIP mutation in the context of the viral genome, we generated recombinant viruses lacking the coding sequence (CDS) of vFLIP gene (K13/ORF71) by bacterial artificial chromosome (BAC) technology and the Escherichia coli Red recombination system...
December 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29207655/egr-1-regulates-rta-transcription-through-a-cooperative-involvement-of-transcriptional-regulators
#8
Roni Sarkar, Subhash C Verma
Kaposi's sarcoma associated herpesvirus (KSHV) regulates the host cellular environment to establish life-long persistent infection by manipulating cellular signaling pathways, with approximately 1- 5% of cells undergoing lytic reactivation during the course of infection. Egr-1 (Early Growth Response Factor-1) is one such cellular transcription factor, which gets phosphorylated during the lytic phase of viral life cycle to perpetrate its function. This study demonstrates the mechanism of how Egr-1 mediates transcription of the immediate early gene, RTA (Replication and transcription activator), which is the lytic switch gene of KSHV...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207182/antitumor-activity-of-the-synthetic-retinoid-st1926-on-primary-effusion-lymphoma-in-vitro-and-in-vivo-models
#9
Louna Karam, Bilal Houshaymi, Rana Abdel-Samad, Mariam Jaafar, Iman Halloum, Claudio Pisano, Frank Neipel, Nadine Darwiche, Raghida Abou Merhi
Primary effusion lymphoma (PEL) is a rare B-cell neoplasm, associated with Kaposi sarcoma-associated herpes virus/human herpes virus-8 (KSHV/HHV-8), arising as malignant effusions in body cavities. PEL cells do not harbor conventional genetic cancer mutations; however, their oncogenesis is mainly attributed to HHV-8 latent genes. Treatment strategies are inefficient resulting in poor prognosis of PEL patients, stressing the need for new effective therapy. ST1926 is a synthetic retinoid with favorable antitumor properties and no cross-resistance with the natural retinoid, all-trans retinoic acid...
December 5, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29207179/arctigenin-induces-the-apoptosis-of-primary-effusion-lymphoma-cells-under-conditions-of-glucose-deprivation
#10
Yusuke Baba, Zenpei Shigemi, Naoko Hara, Misato Moriguchi, Marina Ikeda, Tadashi Watanabe, Masahiro Fujimuro
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and Kaposi's sarcoma. PEL is a type of non-Hodgkin's B-cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or AIDS patients. However, since PEL is resistant to chemotherapeutic regimens, new effective treatment strategies are required. Arctigenin, a natural lignan compound found in the plant Arctium lappa, has been widely investigated as a potential anticancer agent in the clinical setting...
December 1, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29191533/oncogenic-viruses-in-skull-base-chordomas
#11
Youssef Yakkioui, Ernst-Jan M Speel, Jacobus J Van Overbeeke, Merel J M Boderie, Sreedhar Pujari, Axel Zur Hausen, Petra F G Wolffs, Yasin Temel
BACKGROUND: Chordomas are rare tumors assumed to derive from notochordal remnants. We believe that a molecular switch is responsible for their malignant behaviour. However, the involvement of oncogenic viruses has not been studied. Thus, in the present study we investigate the presence of oncogenic viruses in chordomas. METHODS: DNA and RNA from 18 snap-frozen chordomas and 15 chondrosarcomas were isolated. Real-time PCR or RT-PCR was performed to assess the presence of multiple oncogenic viruses, including herpesviridea (HSV1, HSV2,EBV, CMV, HHV6, HHV7 and KSHV), polyomaviridea (PVB19, BK, JC, SV40, MCPyV, HPyV6 and HPyV7), papillomaviridae and respiratory viruses...
November 27, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29184003/il-10-promoter-transactivation-by-the-viral-k-rta-protein-involves-the-host-cell-transcription-factors-specificity-protein-1-and-3
#12
Masanori Miyazawa, Kohji Noguchi, Mana Kujirai, Kazuhiro Katayama, Satoshi Yamagoe, Yoshikazu Sugimoto
Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) causes a persistent infection, presenting latent and lytic replication phases during its life cycle. KSHV-related diseases are associated with deregulated expression of inflammatory cytokines, including IL-6 and IL-10, but the mechanisms underlying this dysregulation are unclear. Herein, we report a molecular mechanism for KSHV-induced IL-10 gene expression. KSHV replication and transcription activator (K-RTA) is a molecular switch for the initiation of expression of viral lytic genes, and we describe, for the first time, that K-RTA significantly activates the promoter of the human IL-10 gene...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29179721/apigenin-by-activating-p53-and-inhibiting-stat3-modulates-the-balance-between-pro-apoptotic-and-pro-survival-pathways-to-induce-pel-cell-death
#13
Marisa Granato, Maria Saveria Gilardini Montani, Roberta Santarelli, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
BACKGROUND: Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against a variety of solid and haematological cancers. In this study, we investigated the effect of apigenin against primary effusion lymphoma (PEL), a KSHV-associated B cell lymphoma characterized by a very aggressive behavior, displaying constitutive activation of STAT3 as well as of other oncogenic pathways and harboring wtp53. METHODS: Cell death was assessed by trypan blue exclusion assay, FACS analysis as well as by biochemical studies...
November 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29167347/a-novel-role-of-vbcl2-in-the-virion-assembly-of-kaposi-s-sarcoma-associated-herpesvirus
#14
Qiming Liang, Dahai Wei, Brain Chung, Kevin F Brulois, Changrun Guo, Shupeng Dong, Shou-Jiang Gao, Pinghui Feng, Chengyu Liang, Jae U Jung
The viral Bcl-2 homolog (vBcl2) of Kaposi's sarcoma-associated herpesvirus (KSHV) displays efficient anti-apoptotic and anti-autophagic activity through its central BH3 domain, which functions to prolong the lifespan of virus-infected cells and ultimately enhances viral replication and latency. Independent on its anti-apoptotic and anti-autophagic activity, vBcl2 also plays an essential role in KSHV lytic replication through its amino-terminal 11-20 amino acids (aa). Here, we report a novel molecular mechanism of vBcl2-mediated regulation of KSHV lytic replication...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#15
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29157621/treatment-of-kaposi-sarcoma-herpesvirus-associated-multicentric-castleman-disease
#16
REVIEW
Kathryn Lurain, Robert Yarchoan, Thomas S Uldrick
Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. Diagnosis requires a lymph node biopsy. Pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. Rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of over 90% at 5 years...
February 2018: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/29116591/prevalence-of-kaposi-s-sarcoma-associated-herpesvirus-in-uygur-and-han-populations-from-the-urumqi-and-kashgar-regions-of-xinjiang-china
#17
Jun Zheng, Yang Yang, Meng Cui, Zhan-Jun Shu, Li-Li Han, Zhen-Qiu Liu, Charles Wood, Tiejun Zhang, Yan Zeng
Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious etiologic agent associated with Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. It has been shown that high KSHV prevalence and high incidence of both classic KS and AIDSassociated KS are found mostly among people of Uygur ethnicity in Xinjiang, while people of Han ethnicity in Xinjiang have a higher KSHV seroprevalence than those of other Han populations in mainland China. However, it is still unclear why there is such geographical and population variation in KSHV distribution in China...
October 2017: Virologica Sinica
https://www.readbyqxmd.com/read/29116588/the-regulatory-role-of-protein-phosphorylation-in-human-gammaherpesvirus-associated-cancers
#18
REVIEW
Yuyan Wang, Shuvomoy Banerjee, Ling Ding, Cankun Cai, Fang Wei, Qiliang Cai
Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation, and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection...
October 2017: Virologica Sinica
https://www.readbyqxmd.com/read/29113328/diabetes-and-risk-of-kaposi-s-sarcoma-effects-of-high-glucose-on-reactivation-and-infection-of-kaposi-s-sarcoma-associated-herpesvirus
#19
Pey-Jium Chang, Yao-Hsu Yang, Pau-Chung Chen, Lee-Wen Chen, Shie-Shan Wang, Ying-Ju Shih, Li-Yu Chen, Chi-Jen Chen, Chien-Hui Hung, Chun-Liang Lin
Patients with diabetes are generally prone to pathogen infection and tumor progression. Here, we investigated the potential association between diabetes and Kaposi's sarcoma (KS), a tumor linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). By using Taiwan's National Health Insurance Research Database, we found that diabetes is statistically associated with increased risk of KS in a case-control study. Since a high level of blood sugar is the hallmark of diabetes, we determined whether high glucose promotes both KSHV reactivation and infection, which are crucial for KS pathogenesis...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109479/viral-and-cellular-n6-methyladenosine-and-n6-2-o-dimethyladenosine-epitranscriptomes-in-the-kshv-life-cycle
#20
Brandon Tan, Hui Liu, Songyao Zhang, Suzane Ramos da Silva, Lin Zhang, Jia Meng, Xiaodong Cui, Hongfeng Yuan, Océane Sorel, Shao-Wu Zhang, Yufei Huang, Shou-Jiang Gao
N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) modifications (m6A/m) of messenger RNA mediate diverse cellular functions. Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) has latent and lytic replication phases that are essential for the development of KSHV-associated cancers. To date, the role of m6A/m in KSHV replication and tumorigenesis is unclear. Here, we provide mechanistic insights by examining the viral and cellular m6A/m epitranscriptomes during KSHV latent and lytic infection...
January 2018: Nature Microbiology
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