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https://www.readbyqxmd.com/read/28053098/the-viral-bcl-2-homologs-of-kaposi-s-sarcoma-associated-herpesvirus-and-rhesus-rhadinovirus-share-an-essential-role-for-viral-replication
#1
Antonio Gallo, Melanie Lampe, Thomas Günther, Wolfram Brune
: KS-Bcl-2 is a Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral Bcl-2 homolog (vBcl-2), which has apoptosis and autophagy inhibiting activity when expressed in transfected cells. However, little is known about its function during viral infection. As KS-Bcl-2 is expressed during the lytic replication cycle, we used constitutively lytic and inducible-lytic KSHV mutants to investigate the role of KS-Bcl-2 during the lytic cycle. We show that KSHV cannot complete the lytic replication cycle and produce infectious progeny in the absence of KS-Bcl-2, indicating that the protein is essential for KSHV replication...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28046107/rna-sequencing-reveals-that-kaposi-sarcoma-associated-herpesvirus-infection-mimics-hypoxia-gene-expression-signature
#2
Coralie Viollet, David A Davis, Shewit S Tekeste, Martin Reczko, Joseph M Ziegelbauer, Francesco Pezzella, Jiannis Ragoussis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28035362/mir-628-3p-regulates-osteoblast-differentiation-by-targeting-runx2-possible-role-in-atrophic-non-union
#3
Hua Chen, Xinran Ji, Fei She, Yuan Gao, Peifu Tang
Atrophic non-union is a serious complication of fractures. The underlying biological mechanisms involved in its pathogenesis are not yet completely understood. MicroRNAs (miRNAs or miRs) are a type of endogenous small non-coding RNA, which participate in various physiological and pathophysiological processes. In this study, differentially expressed miRNAs were screened in patients with atrophic non-union. In total, 4 miRNAs (miR‑149*, miR‑221, miR‑628-3p and miR‑654-5p) were upregulated and 7 miRNAs (let-7b*, miR‑220b, miR‑513a-3p, miR‑551a, miR‑576-5p, miR‑1236 and kshv-miR‑K12-6-5p) were downregulated at the fracture sites in patients with atrophic non-union...
December 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28004818/3-d-microwell-array-system-for-culturing-virus-infected-tumor-cells
#4
Rami El Assal, Umut A Gurkan, Pu Chen, Franceline Juillard, Alessandro Tocchio, Thiruppathiraja Chinnasamy, Chantal Beauchemin, Sebnem Unluisler, Serli Canikyan, Alyssa Holman, Srikar Srivatsa, Kenneth M Kaye, Utkan Demirci
Cancer cells have been increasingly grown in pharmaceutical research to understand tumorigenesis and develop new therapeutic drugs. Currently, cells are typically grown using two-dimensional (2-D) cell culture approaches, where the native tumor microenvironment is difficult to recapitulate. Thus, one of the main obstacles in oncology is the lack of proper infection models that recount main features present in tumors. In recent years, microtechnology-based platforms have been employed to generate three-dimensional (3-D) models that better mimic the native microenvironment in cell culture...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939840/niclosamide-inhibits-lytic-replication-of-epstein-barr-virus-by-disrupting-mtor-activation
#5
Lu Huang, Mengtian Yang, Yan Yuan, Xiaojuan Li, Ersheng Kuang
Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27936107/structural-analysis-of-thymidylate-synthase-from-kaposi-s-sarcoma-associated-herpesvirus-with-the-anticancer-drug-raltitrexed
#6
Yong Mi Choi, Hyun Ku Yeo, Young Woo Park, Jae Young Lee
Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1...
2016: PloS One
https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#7
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27932611/kaposi-s-sarcoma-associated-herpesvirus-infection-of-neurons-in-hiv-positive-patients
#8
For Yue Tso, Ashley Sawyer, Eun Hee Kwon, Victor Mudenda, Dianne Langford, You Zhou, John West, Charles Wood
BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS), one of the leading cancers in HIV patients in Zambia. KSHV was detected in the human central nervous system (CNS) by PCR, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV positive individuals with KSHV, we sought to determine whether the CNS can be infected by KSHV in HIV positive Zambian individuals...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27928018/expression-of-the-antisense-to-latency-transcript-long-noncoding-rna-in-kaposi-s-sarcoma-associated-herpesvirus
#9
Jason M Schifano, Kathleen Corcoran, Hemant Kelkar, Dirk P Dittmer
: The regulation of latency is central to herpesvirus biology. Recent transcriptome-wide surveys have uncovered evidence for promiscuous transcription across the entirety of the Kaposi sarcoma-associated herpesvirus genome and postulated the existence of multiple viral long noncoding RNAs (lncRNAs). NextGen sequencing studies are highly dependent on the specific experimental approach and particular algorithms of analysis, and therefore benefit from independent confirmation of the results...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27912080/the-itch-ubiquitin-ligase-is-required-for-kshv-rta-induced-vflip-degradation
#10
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...
January 15, 2017: 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
January 2017: Viral Immunology
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