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https://www.readbyqxmd.com/read/27912080/the-itch-ubiquitin-ligase-is-required-for-kshv-rta-induced-vflip-degradation
#1
Jennifer C Chmura, Kevin Herold, Ayana Ruffin, Trudymae Atuobi, Yetunde Fabiyi, Ashley E Mitchell, Young Bong Choi, Elana S Ehrlich
Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA...
November 29, 2016: Virology
https://www.readbyqxmd.com/read/27893813/azidothymidine-sensitizes-primary-effusion-lymphoma-cells-to-kaposi-sarcoma-associated-herpesvirus-specific-cd4-t-cell-control-and-inhibits-virf3-function
#2
Samantha J Williamson, Samantha M Nicol, Michael Stürzl, Shereen Sabbah, Andrew D Hislop
Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27893764/virus-mediated-alterations-in-mirna-factors-and-degradation-of-viral-mirnas-by-mcpip1
#3
Christine Happel, Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation...
November 2016: PLoS Biology
https://www.readbyqxmd.com/read/27890943/recapitulation-of-acquired-immuno-deficiency-syndrome-associated-kaposi-s-sarcoma
#4
REVIEW
Balaji Govindan
Acquired immuno deficiency syndrome (AIDS) associated Kaposi's sarcoma (KS) is one of the clinical forms of KS. KS is caused by human herpes viruses 8 or KS associated herpes virus (KSHV). In India, till now, only 16 cases of AIDS associated KS was reported. Of all the clinical forms of KS, AIDS associated KS is distinct in many ways viz.; cutaneous manifestations commonly affects face and trunk rather than lower limbs, more mucosal lesions, rapidly progressive, and early systemic involvement. When human immunodeficiency virus (HIV) is co-infected with KSHV, in addition to the other pathogenic factors for the development of KS, HIV Tat protein promotes the proliferation of cytokine-activated endothelial cells and stimulates KS...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27872774/pulmonary-kaposi-sarcoma-an-uncommon-cause-of-respiratory-failure-in-the-era-of-highly-active-antiretroviral-therapy-case-report-and-review-of-the-literature
#5
Stanley M Nwabudike, Stefan Hemmings, Yonette Paul, Yordanis Habtegebriel, Octavius Polk, Alem Mehari
Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges...
2016: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/27871174/viral-inhibition-of-prr-mediated-innate-immune-response-learning-from-kshv-evasion-strategies
#6
REVIEW
Hye-Ra Lee, Un Yung Choi, Sung-Woo Hwang, Stephanie Kim, Jae U Jung
The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit...
November 30, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#7
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27853834/proliferation-status-defines-functional-properties-of-endothelial-cells
#8
Christoph Lipps, Muhammad Badar, Milada Butueva, Tatyana Dubich, Vivek Vikram Singh, Sophie Rau, Axel Weber, Michael Kracht, Mario Köster, Tobias May, Thomas F Schulz, Hansjörg Hauser, Dagmar Wirth
Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive...
November 16, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27852859/kshv-micrornas-target-gadd45b-to-protect-infected-cells-from-cell-cycle-arrest-and-apoptosis
#9
Xiaoyan Liu, Christine Happel, Joseph M Ziegelbauer
: Kaposi's sarcoma is one of the most common malignancies in HIV-infected individuals. The responsible agent, Kaposi's sarcoma-associated herpesvirus (KSHV, HHV8) expresses multiple microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. After infection in primary endothelial cells with KSHV, growth arrest DNA damage-inducible gene 45 beta (GADD45B) is one of the most repressed genes using genomic expression profiling. GADD45B was also repressed in mRNA expression profiling experiments when KSHV miRNAs were introduced to uninfected cells...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27832591/a-herpesvirus-protein-selectively-inhibits-cellular-mrna-nuclear-export
#10
Danyang Gong, Yong Hoon Kim, Yuchen Xiao, Yushen Du, Yafang Xie, Kevin K Lee, Jun Feng, Nisar Farhat, Dawei Zhao, Sara Shu, Xinghong Dai, Sumit K Chanda, Tariq M Rana, Nevan J Krogan, Ren Sun, Ting-Ting Wu
Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27830995/oncogenic-role-of-tumor-viruses-in-humans
#11
Nimrah Akram, Muhammad Imran, Mamoona Noreen, Fayyaz Ahmed, Muhammad Atif, Zareen Fatima, Ahmed Bilal Waqar
Viruses are the intracellular pathogens that reproduce only in the living cell and manipulate the cellular machinery to produce more viruses. Viral replications can affect cellular genes of the host in multiple cancerous ways. Approximately, 20% of all human oncogenesis is caused by cancer-causing viruses known as oncoviruses. Viral infection causes chronic inflammation leading to cell death, uncontrollable proliferation, and modulated expression of some of the regulatory proteins. Oncogenesis is a multistep phenomenon in which normal host cells are transformed into cancerous cells on the basis of host genetic variability...
November 10, 2016: Viral Immunology
https://www.readbyqxmd.com/read/27829174/a-chimeric-protein-composed-of-numa-fused-to-the-dna-binding-domain-of-lana-is-sufficient-for-the-ori-p-dependent-dna-replication
#12
Eriko Ohsaki, Keiji Ueda
The Kaposi's sarcoma-associated herpesvirus (KSHV) genome is stably maintained in KSHV-infected PEL cell lines during cell division. We previously showed that accumulation of LANA in the nuclear matrix fraction could be important for the latent DNA replication, and that the functional significance of LANA should be its recruitment of ori-P to the nuclear matrix. Here, we investigated whether the forced localization of the LANA-DNA binding domain (DBD) to the nuclear matrix facilitated ori-P-containing plasmid replication...
November 6, 2016: Virology
https://www.readbyqxmd.com/read/27829024/the-kshv-k1-protein-modulates-ampk-function-to-enhance-cell-survival
#13
Penny M Anders, Zhigang Zhang, Prasana M Bhende, Louise Giffin, Blossom Damania
Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS) as well as two lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV encodes viral proteins, such as K1, that alter signaling pathways involved in cell survival. Expression of K1 has been reported to transform rodent fibroblasts, and K1 transgenic mice develop multiple tumors, suggesting that K1 has an important role in KSHV pathogenesis. We found that cells infected with a KSHV virus containing a WT K1 gene had a survival advantage under conditions of nutrient deprivation compared to cells infected with KSHV K1 mutant viruses...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27807232/structure-of-the-opening-reading-frame-49-protein-encoded-by-kaposi-s-sarcoma-associated-herpesvirus-kshv
#14
Kelly Hew, Saranya Veerappan, Daniel Sim, Tobias Cornvik, Pär Nordlund, Sue-Li Dahlroth
: Herpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for the herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in KSHV. The protein encoded by open reading frame 49 from KSHV (ORF49KSHV) has been shown to up-regulate lytic replication in KSHV by enhancing the activities of the replication and transcription activator (RTA)...
November 2, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27798559/targeting-the-atp-dependent-formation-of-herpesvirus-ribonucleoprotein-particle-assembly-as-an-antiviral-approach
#15
Sophie Schumann, Brian R Jackson, Ian Yule, Steven K Whitehead, Charlotte Revill, Richard Foster, Adrian Whitehouse
Human herpesviruses are responsible for a range of debilitating acute and recurrent diseases, including a number of malignancies. Current treatments are limited to targeting the herpesvirus DNA polymerases, but with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. Here, we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs)...
October 31, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27796928/latent-kaposi-s-sarcoma-associated-herpesvirus-infection-in-bladder-cancer-cells-promotes-drug-resistance-by-reducing-reactive-oxygen-species
#16
Suhyuk Lee, Jaehyuk Jang, Hyungtaek Jeon, Jisu Lee, Seung-Min Yoo, Jinsung Park, Myung-Shin Lee
Kaposi's sarcoma-associated herpesvirus (KSHV) is the major etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Recent studies have indicated that KSHV can be detected at high frequency in patient-derived bladder cancer tissue and might be associated with the pathogenesis of bladder cancer. Bladder cancer is the second most common cancer of the genitourinary tract, and it has a high rate of recurrence. Because drug resistance is closely related to chemotherapy failure and cancer recurrence, we investigated whether KSHV infection is associated with drug resistance of bladder cancer cells...
November 2016: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27795414/identification-of-novel-kshv-orf50-transcripts-discovery-of-new-rta-isoforms-with-variable-transactivation-potential
#17
Brian S Wakeman, Yoshihiro Izumiya, Samuel H Speck
: Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma, multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50. RTA is a known transactivator of multiple viral genes allowing for it to control the switch between latency and virus replication...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27780949/alterations-in-acetylation-of-histone-h4-lysine-8-and-trimethylation-of-lysine-20-associated-with-lytic-gene-promoters-during-kaposi-s-sarcoma-associated-herpesvirus-reactivation
#18
Sora Lim, Seho Cha, Jun Hyeong Jang, Dahye Yang, Joonho Choe, Taegun Seo
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with formation of Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Replication and transcription activator (RTA) genes are expressed upon reactivation of KSHV, which displays a biphasic life cycle consisting of latent and lytic replication phases. RTA protein expression results in KSHV genome amplification and successive viral lytic gene expression. Transcriptional activity of viral lytic genes is regulated through epigenetic modifications...
October 25, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27764250/histone-h2b-ifi16-recognition-of-nuclear-herpesviral-genome-induces-cytoplasmic-interferon-%C3%AE-responses
#19
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27764233/escrt-i-protein-tsg101-plays-a-role-in-the-post-macropinocytic-trafficking-and-infection-of-endothelial-cells-by-kaposi-s-sarcoma-associated-herpesvirus
#20
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
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